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  • Collagen‐I/silk‐fibroin biocomposite exhibits microscalar confinement of cells and induces anisotropic morphology and migration of embedded fibroblasts
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-26
    Subhajit Konar; Privita Edwina; Vaibavi Ramanujam; Arockiarajan Arunachalakasi; Saumendra Kumar Bajpai

    Microstructural anisotropy of tumor‐associated matrix correlates with invasion of cancer cells into the surrounding matrix during metastasis. Here, we report the fabrication and characterization of a three‐dimensional (3D) silk‐fibroin/collagen‐I bio‐composite based cell‐culture model that exhibits microstructural and biochemical anisotropy. Using RGD‐deficient silk‐fibroin fibers to confine collagen‐I gelation, we develop a silk‐fibroin/collagen‐I (SFC) bio‐composite in a one‐step process allowing control over the microstructural and biochemical anisotropy and the pore‐size. Two forms of the SFC bio‐composite are reported: a sandwich (Sfc) configuration amenable to live‐cell microscopy and an unsupported membrane (Mfc) for use as a scaffold. Both microscalar and macroscalar mechanical properties of the SFC bio‐composite are characterized using atomic force microscope (AFM)‐based indentation and tensile‐testing. We find that the modulus of stiffness of both Sfc and Mfc can be controlled and falls in the physiological range of 5–20 kPa. Furthermore, the modulus of stiffness of Mfc exhibits a ~200% increase in axial direction of microstructure, as compared to lateral direction. This implies a highly anisotropic mechanical stiffness of the microenvironment. Live‐cell morphology and migration studies show that both the morphology and the migration of NIH‐3 T3 fibroblasts is anisotropic and correlates with microstructural anisotropy. Our results show that SFC bio‐composite permits proliferation of cells in both Sfc and Mfc configuration, promotes cell‐migration along the major axis of anisotropy and together with morphological and migration data, suggest a potential application of both the composite configurations as a biomimetic scaffold for tissue engineering applications.

    更新日期:2020-01-27
  • Engineering a collagen matrix for cell‐instructive regenerative angiogenesis
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-26
    Alicia J. Minor; Kareen L. K. Coulombe

    Engineering an angiogenic material for regenerative medicine requires knowledge of native extracellular matrix remodeling by cellular processes in angiogenesis. Vascularization remains a key challenge in the field of tissue engineering, one that can be mitigated by developing platforms conducive to guiding dynamic cell‐matrix interactions required for new vessel formation. In this review, we highlight nuanced processes of angiogenesis and demonstrate how materials engineering is being used to interface with dynamic type I collagen remodeling, Notch and VEGF signaling, cell migration, and tissue morphogenesis. Because α1(I)‐collagen is secreted by endothelial tip cells during sprouting angiogenesis and required for migration, collagen is a very useful natural biomaterial and its angiogenic modifications are described. The balance between collagen types I and IV via secretion and degradation is tightly controlled by proteinases and other cell types that are capable of internalizing collagen to maintain tissue integrity. Thus, we provide examples in skin and cardiac tissue engineering of collagen tailoring in diverse cellular microenvironments for tissue regeneration. As our understanding of how to drive collagen remodeling and cellular phenotype through angiogenic pathways grows, our capabilities to model and manipulate material systems must continue to expand to develop novel applications for wound healing, angiogenic therapy, and regenerative medicine.

    更新日期:2020-01-27
  • Enhanced osteogenic differentiation of human mesenchymal stromal cells as response to periodical microstructured Ti6Al4V surfaces
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-25
    Simon Janßen; Stefan Gach; Sebastian Kant; Sanja Aveic; Stephan Rütten; Simon Olschok; Uwe Reisgen; Horst Fischer
    更新日期:2020-01-26
  • Radioprotection and cross‐linking of allograft bone in the presence of vitamin E
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-24
    Jeremy V. Suhardi; David F. A. Morgan; Orhun K. Muratoglu; Ebru Oral

    Bone allografts are the preferred method for bone augmentation in over 500,000 orthopedic surgical procedures in the US. Sterilization by ionizing radiation is the most effective method of minimizing the bioburden of bone allografts; however, radiation causes chain scission of collagen, resulting in the reduction of the allografts’ mechanical strength. In this study, we doped bone allografts with vitamin E as radioprotectant using a novel two‐step process to protect the collagen architecture against radiation damage and to preserve the mechanical strength of the construct. In addition, combining the radioprotectant with a cross‐linking agent further minimized collagen degradation and further preserved the mechanical strength of the allografts. Both vitamin E and combined vitamin E/genipin‐treated allograft were less cytotoxic to both osteoblasts and osteoclasts when compared to irradiated‐only allografts. Host bone‐allograft unionization was faster in a rat calvaria defect model with vitamin E‐treated and combined vitamin E and genipin‐treated allograft when compare to irradiated‐only allografts. This method can enable the efficient and uniform radioprotective treatment of bone allograft of desired shapes for sterilization with improved mechanical strength and biointegration.

    更新日期:2020-01-24
  • Use of chitosan as pharmaceutical excipient in ocular drug delivery systems: Sterilization and pharmacokinetics
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-22
    Juçara R. Franca; Leonardo L. Fuscaldi; Tatiana G. Ribeiro; Giselle Foureaux; Aina L. A. Cesar; Rachel O. Castilho; Sebastião Cronemberger; Anderson J. Ferreira; Simone O. A. Fernandes; Valbert N. Cardoso; André A. G. Faraco

    The use of chitosan as a pharmaceutical excipient in the ocular field is already established. Nevertheless, some aspects related to its ocular administration, such as sterilization and excipient's pharmacokinetics, remain unclear. So, in this study, we evaluated those two relevant aspects, related to chitosan administration in eye. We used chitosan‐based ocular inserts (CI) as formulation model. CI were produced by solvent/casting method and sterilized by saturated steam. Sterilization was confirmed by direct inoculation of inserts in suitable microbiological growth media. Physicochemical characterization of inserts before and after sterilization was performed. Results suggested that, although steam sterilization changed the arrangement of the matrix, the heat and the humidity did not modify the structure of the main polymeric chain. Pharmacokinetics of CI radiolabeled with technetium‐99m (99mTc) was assessed by scintigraphic images and ex vivo biodistribution study, after ocular administration in male Wistar rats. Scintigraphic and images analysis and ex vivo biodistribution study showed that the insert remained mainly in the eye until 6 hr after administration and its degradation products began to migrate to the abdominal cavity after 18 hr. Together, these data represent an important step forward the manufacturing and the clinical application of CI in the ophthalmic field.

    更新日期:2020-01-23
  • Etching anisotropic surface topography onto fibrin microthread scaffolds for guiding myoblast alignment
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-22
    Meagan E. Carnes; George D. Pins

    To regenerate functional muscle tissue, engineered scaffolds should impart topographical features to induce myoblast alignment by a phenomenon known as contact guidance. Myoblast alignment is an essential step towards myotube formation, which is guided in vivo by extracellular matrix structure and micron‐scale grooves between adjacent muscle fibers. Fibrin microthread scaffolds mimic the morphological architecture of native muscle tissue and have demonstrated promise as an implantable scaffold for treating skeletal muscle injuries. While these scaffolds promote modest myoblast alignment, it is not sufficient to generate highly functional muscle tissue. The goal of this study is to develop and characterize a new method of etching the surface of fibrin microthreads to incorporate aligned, sub‐micron grooves that promote myoblast alignment. To generate these topographic features, we placed fibrin microthreads into 2‐(N‐morpholino)ethane‐sulfonic acid (MES) acidic buffer and evaluated the effect of buffer pH on the generation of these features. Surface characterization with atomic force microscopy and scanning electron microscopy indicated the generation of aligned, sub‐micron sized grooves on microthreads in MES buffer with pH 5.0. Microthreads etched with surface features had tensile mechanical properties comparable to controls, indicating that the surface treatment does not inhibit scaffold bulk properties. Our data demonstrate that etching threads in MES buffer with pH 5.0 enhanced alignment and filamentous actin stress fiber organization of myoblasts on the surface of scaffolds. The ability to tune topographic features on the surfaces of scaffolds independent of mechanical properties provides a valuable tool for designing microthread‐based scaffolds to enhance regeneration of functional muscle tissue.

    更新日期:2020-01-23
  • Improved tissue integration of a new elastic intraperitoneal stoma mesh prosthesis
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-22
    Roman Eickhoff; Daniel Heise; Andreas Kroh; Marius Helmedag; Uwe Klinge; Ulf P. Neumann; Christian D. Klink; Andreas Lambertz

    Parastomal herniation is a frequent complication in colorectal surgery, occurring with a prevalence of 30–80%. The aim of the study was to create a new intraperitoneal colostoma mesh prosthesis (IPST) with enhanced elastic properties made with thermoplastic polyurethane (TPU) monofilaments. We performed open terminal sigmoid colostomies reinforced with either a 10 cm by 10 cm polyvinylidene fluoride (PVDF) or a new TPU/PVDF composite mesh in a total of 10 minipigs. Colostoma was placed paramedian in the left lower abdomen and IPST meshes were fixed intraperitoneal. After 8 weeks, the animals were euthanized after laparoscopic exploration and specimen were explanted for histological investigations. Implantation of a new IPST‐mesh with enhanced elastic properties was feasible in a minipig model within an observation period of 8 weeks. Immunohistochemically, Collagen I/III ratio as a marker of tissue integration was significantly higher in TPU‐group versus PVDF group (9.4 ± 0.5 vs. 8.1 ± 0.5, p = 0.002) with a significantly lower inflammatory reaction measured by a smaller inner granuloma at mesh–colon interface (17.6 ± 3.3 μm vs. 23 ± 5 μm, p < 0.001). A new TPU/PVDF composite mesh with enhanced elastic properties as IPST was created. Stoma surgery and especially the evaluation of the new stoma mesh prosthesis are feasible with reproducible results in an animal model. Tissue integration expressed by Collagen I/III ratio seems to be improved in comparison to standard‐elastic PVDF‐IPST meshes.

    更新日期:2020-01-23
  • Development of an automated micropipette coating method for drug‐coated balloons
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-22
    Kirby Fuglsby; Jordan A. Anderson; Daniel Engebretson; Sujan Lamichhane

    Drug‐coated balloons (DCBs) are a recent technology developed to treat peripheral artery disease (PAD). Along with a suitable formulation of antiproliferative drug and excipient, coating method is an important aspect of a DCB as these factors affect coating characteristics and drug delivery to the treatment site. The multiple release tailored medical devices DCB (MR‐TMD‐DCB), designed to achieve multiple inflations to treat complex PAD, contains paclitaxel (PAT) as the antiproliferative drug and polyethylene oxide (PEO) as the excipient. In our previous studies, the MR‐TMD‐DCB was coated using a manual dip coating method. In this study, an automated micropipette coating method was developed using a modified spray coating instrument to coat the MR‐TMD‐DCB. First, the coating formulation and strategy was optimized. A drug formulation of 16 wt% PAT and 4% wt/vol PEO, a polymer formulation of 2.5% wt/vol PEO, and a total of two drug layers produced a mostly uniform and thin coating with no defects and acceptable drug load. The balloon also had optimal drug uptake in arterial tissue in an in vitro flow model. Next, the reproducibility of the coating strategy was improved by optimizing the instrument parameters. The optimized instrument parameters (translational speed = 0.150 in/s, revolution rate = 100 rpm, flow rate = 0.6 ml/min) resulted in improved reproducibility of the drug load and similar coating properties as the DCB. This study demonstrated the ability to automate the micropipette process to obtain a balloon with optimal coating properties and drug tissue uptake.

    更新日期:2020-01-23
  • Fabrication, characterization, and in vitro evaluation of electrospun polyurethane‐gelatin‐carbon nanotube scaffolds for cardiovascular tissue engineering applications
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-22
    Farbod Tondnevis; Hamid Keshvari; Jamshid Aghazadeh Mohandesi

    Myocardial infarction occurs because coronary arteries insufficiency is one of the major causes of mortality worldwide. Recent studies have shown that tissue engineering of myocardial tissue to regenerate infarcted tissue or engineering of the coronary artery may help overcome this problem. In the present research, gelatin and single‐walled carbon nanotube were firstly administrated to physico‐chemically and biologically modulate polyurethane nanofibers. Electrospinning, as versatile and effective technique for production of functional nanoscale fiber, was applied. Incorporation of both gelatin and SWNTs reduced mean diameter of nanofibrous scaffolds from 210 to 140 nm, which influenced on initial cell behavior. Possible interaction between gelatin and SWNTs with polyurethane chains was evaluated using FTIR and DSC techniques. Regarding the incorporation of both gelatin and SWNTs, it was found that hydrophilicity of nanofibrous scaffolds dramatically improved. Scaffold degradation profile was adjusted by incorporation of gelatin. Biomimetic mechanical properties of composite scaffolds like normal blood vessel were developed and SWNTs improved the Young modulus and ultimate strength of scaffolds up to 16.47 ± 0.5 and 23.73 ± 0.5 MPa, respectively. However, addition of gelatin increased elongation at break due to its softening effect. The incorporation of the SWNTs led to significant enhancement of electrical conductivity of the scaffolds. Biological evaluation using SEM and MTT assay demonstrated that nanofibrous surface was covered by confluent and dense layer of both myocardial myoblast and endothelial cells after 7 days of culture, which is crucial for cardiovascular tissue engineering. Results verified that the fabricated scaffolds could be effective for cardiovascular tissue engineering.

    更新日期:2020-01-23
  • Micro‐CT and histopathology methods to assess host response of aneurysms treated with shape memory polymer foam‐coated coils versus bare metal coil occlusion devices
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-21
    Staci L. Jessen; Molly C. Friedemann; Annmarie E. Mullen; Anne‐Marie Ginn‐Hedman; Scott M. Herting; Duncan J. Maitland; Fred J. Clubb

    Recent studies utilizing shape memory polymer foams to coat embolizing coils have shown potential benefits over current aneurysm treatments. In the current study utilizing a rabbit‐elastase aneurysm model, the performance of test article (foam‐coated coil [FCC]) and control (bare platinum coils [BPCs]) devices were compared at 30, 90, and 180 days using micro‐CT and histological assessments. The host response was measured by identifying the cells regionally present within the aneurysm, and assessing the degree of residual debris and connective tissue. The 3D reconstructions of aneurysms provided context for histologic findings, and aided in the overall aneurysm assessment. At all time points, >75% of the cells categorized in each aneurysm were associated with a bioactive yet biocompatible host response (vs. the remainder of cells that were associated with acute inflammation). The extracellular matrix exhibited a transition from residual fibrin at 30 days to a greater degree of connective tissue at 90 and 180 days. Although the control BPC‐treated aneurysms exhibited a greater degree of connective tissue at the earliest time point examined (30 days), by 180 days, the FCC‐treated aneurysms had more connective tissue and less debris overall than the control aneurysms. When considering cell types and extracellular matrix composition, the overall host response scores were significantly better in FCC‐treated aneurysms at the later time point. Based on the results of these metrics, the FCC device may lead to an advanced tissue remodeling response over BPC occlusion devices.

    更新日期:2020-01-22
  • An innovative occluder for cardiac defect: 3D printing and a biocompatibility research based on self‐developed bioabsorbable material—LA–GA–TMC
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-21
    Yiming Sun; Yinghui Xia; Xingjian Zhang; Wenjing Li; Quansheng Xing

    This study adopted the latest self‐developed bioabsorbable material lactide–glycolide–1,3‐trimethylene carbonate (LA–GA–TMC) and applied the three‐dimensional (3D) printing technique to manufacture the occluder for cardiac septal defects, so as to realize the individualized treatment of cardiac septal defects. At the same time, its biosafety was evaluated, with an aim to establish foundation for futural large‐scale animal experiment and clinical trial. The traditional “one‐pot synthesis” was modified, and the “two‐step synthesis method” was utilized to synthesize the LA–GA–TMC terpolymer at the lactide: glycolide: trimethylene carbonate ratio of 6:1:1.7. Afterward, the synthesized terpolymer was used as the raw material to fabricate the occluder model via using 3D printing technique. Then, its biocompatibility was comprehensively evaluated through cytocompatibility, blood compatibility, and histocompatibility. The occluder made from LA–GA–TMC 3D printing had favorable ductility and recoverability; besides, it possessed the temperature‐control feature, and the relative cell proliferation rates in extract liquids at various concentrations were all >70%, suggesting that it had favorable cytocompatibility. Moreover, hemolytic experiment revealed that its hemolytic rate was <5%, dynamic blood coagulation experiment demonstrated that the sample material moderately activated the blood coagulation, and the above findings suggested that it had good blood compatibility. In addition, implanting experiment in vivo revealed that its histocompatibility was superior to the traditional nitinol and the emerging poly‐l‐lactic acid. It is completely feasible to manufacture the cardiac septal defects occluder based on the novel absorbable material LA–GA–TMC, which has favorable biocompatibility, through 3D printing technique and it possesses broad prospects in large‐scale animal experiment and clinical trial.

    更新日期:2020-01-22
  • Synthesis and characterization of thiol‐acrylate hydrogels using a base‐catalyzed Michael addition for 3D cell culture applications
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-21
    Anowar H. Khan; Jeffery K. Cook; Wayne J. Wortmann; Nathan D. Kersker; Asha Rao; John A. Pojman; Adam T. Melvin

    There is significant interest in developing new approaches for culturing mammalian cells in a three‐dimensional (3D) environment due to the fact that it better recapitulates the in vivo environment. The goal of this work was to develop thiol‐acrylate, biodegradable hydrogels that possess highly tunable properties to support in vitro 3D culture. Six different hydrogel formulations were synthesized using two readily available monomers, a trithiol (ETTMP 1300 [ethoxylated trimethylolpropane tri(3‐mercaptopropionate) 1300]) and a diacrylate (PEGDA 700 [polyethylene glycol diacrylate 700]), polymerized by a base‐catalyzed Michael addition reaction. The resultant hydrogels were homogeneous, hydrophilic, and biodegradable. Different mechanical properties such as gelation time, storage modulus (or the elasticity G'), swelling ratio, and rate of degradation were tuned by varying the weight percentage of polymer, the molar ratio of thiol‐to‐acrylate groups, and the pH of the solution. Cytocompatibility was assessed using two model breast cancer cell lines by both 2D and 3D cell culturing approaches. The hydrogel formulations with a thiol‐to‐acrylate molar ratio of 1.05 were found to be optimal for both 2D and 3D cultures with MDA‐MB‐231 cellular aggregates found to be viable after 17 days of 3D continuous culture. Finally, MCF7 cells were observed to form 3D spheroids up to 600 μm in diameter as proof of principle for the thiol‐acrylate hydrogel to function as a scaffold for in vitro 3D cell culture. A comparison of the different mechanical properties of the six hydrogel formulations coupled with in vitro cell culture results and findings from previously published hydrogels conclude that the thiol‐acrylate hydrogels have significant potential as a scaffold for 3D cell culture.

    更新日期:2020-01-22
  • 更新日期:2020-01-17
  • Porous titanium fiber mesh with tailored elasticity and its effect on stromal cells
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-14
    Evy Aerts; Jinmeng Li; Mies J. Van Steenbergen; Tanika Degrande; John A. Jansen; X. Frank Walboomers

    Porous titanium fiber mesh (TFM) is considered a suitable scaffold material for bone reconstruction. Also, TFM can be used to cover the surface of bone‐anchored devices, that is, orthopedic or dental implants. The titanium fiber size has an effect of the stiffness as well as porosity of the titanium mesh, which can influence the behavior of bone forming cells. Therefore, the aim of this study was to vary TFM composition, in order to achieve different stiffness, and to assess the effects of such variation on the behavior of bone marrow‐derived stromal cells (BMSCs). With that purpose, nine types of TFM (porosities 60–87%; fiber size 22–50 μm), were examined for their mechanical properties as well as their effect on the proliferation and differentiation of rat bone marrow‐derived stromal cells (rBMSCs) up to 21 days. Dynamic mechanical analysis revealed that the stiffness of TFM were lower than of solid titanium and decreased with larger fiber sizes. The stiffness could effectively be tailored by altering fiber properties, which altered the pore simultaneously. For the 22 and 35 μm size fiber meshes with the highest porosity, the stiffness closely matched the value found in literature for cortical bone. Finally, all tested TFM types supported the growth and differentiation of rBMSCs. We concluded that TFM material has been proven cytocompatible. Further preclinical studies are needed to assess which TFM type is most suitable as clinical use for bone ingrowth and bone regeneration.

    更新日期:2020-01-14
  • Comprehensive assessment of mechanical behavior of an extremely long stent graft to control hemorrhage in torso
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-14
    Moataz Elsisy; Bryan W. Tillman; Catherine Go; Jenna Kuhn; Sung K. Cho; William W. Clark; Junkyu Park; Youngjae Chun

    Traumatic vascular injuries, resulting from either civilian accidents or wounded soldiers, require new endovascular devices (i.e., stent graft) to rapidly control the excessive internal hemorrhage in torso region. Current stent designs are limited by their permanent nature, which is note well suited for emergent placement. A retrievable stent graft could regulate the internal bleeding temporarily, as fast as possible with the most feasible performance, until the patients arrive the hospital to receive the proper treatment. The novel endovascular device of this study is designed according to the anatomy of a porcine model with plans to transition to a human model in the future. The stent graft is manufactured using a substantially long nitinol backbone and covered selectively based on anatomic measurements, with highly stretchable expanded‐polytetrafluoroethylene (ePTFE). In this study, our group comprehensively explored designing and manufacturing methods, and their impact on the stent graft performance. Geometric parameters and heat treatment conditions were investigated to show their effect on the radial force of the metallic backbone. As a retrievable device, the resistance force for retrieval as well as deployment were measured, and analyzed to be manipulated through ePTFE covering configurations. In vitro measurements for bleeding were measured using swine aorta to show the functionality of the stent graft under the simulated pulsatile flow circulation. Finally, the stent graft showed substantial effectiveness for hemorrhage control in vivo, using swine model. The new design and fabrication methods enable rapid hemorrhage control that can be removed at the time of a dedicated surgical repair.

    更新日期:2020-01-14
  • Thermosensitive hydrogels loaded with human‐induced pluripotent stem cells overexpressing growth differentiation factor‐5 ameliorate intervertebral disc degeneration in rats
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-12
    Annan Hu; Rong Xing; Libo Jiang; Zefang Li; Peng Liu; Houlei Wang; Xilei Li; Jian Dong

    To evaluate the effects of thermosensitive hydrogels loaded with human‐induced pluripotent stem cells transfected with the growth differentiation factor‐5 (GDF5‐hiPSCs) on rat intervertebral disc regeneration. GDF5‐hiPSCs were cocultured with rat nucleus pulposus (NP) cells in vitro. Real‐time PCR and western blot were used to determine the differentiation of hiPSCs. Rat caudal intervertebral discs were punctured using a needle under X‐ray, and groups of coccygeal (Co) discs were subject to various treatments: Puncture group (Co6/7, punctured without treatment); Hydrogel group (Co7/8, 2 μl of hydrogel injected without cells); GDF5‐hiPSCs + Hydrogel group (Co8/9, 2 μl of GDF5‐hiPSCs‐loaded hydrogel injected); and Normal control (Co5/6). X‐ray, MRI, and histological evaluations were performed at 1, 2, and 3 months after cell transplantation and relative changes in the disc height index (DHI%) and voxel count were calculated and compared. GDF5‐hiPSCs were successfully differentiated to a chondrogenic linage after cocultured with rat NP cells. In terms of X‐ray, MRI, and HE staining scores, the GDF5‐hiPSCs + Hydrogel group was significantly superior to the Puncture and Hydrogel groups (p < .05). Compared with the Normal group, the MRI‐based voxel count of the GDF5‐hiPSCs + Hydrogel group was significantly lower at 1, 2, and 3 months after cell transplantation (p < .05). However, there were no significant differences in histological scores at 1 and 2 months after cell transplantation compared with the Normal group (p > .05). In conclusion, thermosensitive hydrogel‐encapsulated hiPSCs overexpressing the GDF5 gene ameliorated intervertebral disc degeneration.

    更新日期:2020-01-13
  • Extracellular matrix decorated polycaprolactone scaffolds for improved mesenchymal stem/stromal cell osteogenesis towards a patient‐tailored bone tissue engineering approach
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-09
    João C. Silva; Marta S. Carvalho; Ranodhi N. Udangawa; Carla S. Moura; Joaquim M. S. Cabral; Cláudia L. da Silva; Frederico Castelo Ferreira; Deepak Vashishth; Robert J. Linhardt

    The clinical demand for tissue‐engineered bone is growing due to the increase of non‐union fractures and delayed healing in an aging population. Herein, we present a method combining additive manufacturing (AM) techniques with cell‐derived extracellular matrix (ECM) to generate structurally well‐defined bioactive scaffolds for bone tissue engineering (BTE). In this work, highly porous three‐dimensional polycaprolactone (PCL) scaffolds with desired size and architecture were fabricated by fused deposition modeling and subsequently decorated with human mesenchymal stem/stromal cell (MSC)‐derived ECM produced in situ. The successful deposition of MSC‐derived ECM onto PCL scaffolds (PCL‐MSC ECM) was confirmed after decellularization using scanning electron microscopy, elemental analysis, and immunofluorescence. The presence of cell‐derived ECM within the PCL scaffolds significantly enhanced MSC attachment and proliferation, with and without osteogenic supplementation. Additionally, under osteogenic induction, PCL‐MSC ECM scaffolds promoted significantly higher calcium deposition and elevated relative expression of bone‐specific genes, particularly the gene encoding osteopontin, when compared to pristine scaffolds. Overall, our results demonstrated the favorable effects of combining MSC‐derived ECM and AM‐based scaffolds on the osteogenic differentiation of MSC, resulting from a closer mimicry of the native bone niche. This strategy is highly promising for the development of novel personalized BTE approaches enabling the fabrication of patient defect‐tailored scaffolds with enhanced biological performance and osteoinductive properties.

    更新日期:2020-01-09
  • Equivalent mechanical properties of X‐ray and E‐beam cross‐linked vitamin E blended ultrahigh molecular weight polyethylene
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-06
    Marie Anne Mulliez; Christoph Schilling; Thomas M. Grupp

    The influence of X‐ray cross‐linking compared with electron beam cross‐linking on the mechanical and thermal properties of UHMWPE blended with 0.1 wt% vitamin E was investigated. Two X‐ray doses (80 and 100 kGy) and two irradiation temperatures (RT: room temperature; 100 °C: warm) were considered. The reference was Vitelene® a vitamin E stabilized UHMWPE cross‐linked with 80 kGy e‐beam at 100°C. Uniaxial tensile and small punch testing were conducted. The Izod impact strength and the thermal properties were determined. The yield, ultimate tensile strength and elongation were 21.7 MPa, 48 MPa, and 393% for Vitelene® and 21.7 MPa, 47 MPa, and 402% for X (80 kGy)‐warm, respectively. The peak load, ultimate displacement, and work to failure accounted for 63 N, 5.7 mm and 331 mJ for Vitelene® and 65 N, 5.6 mm, and 322 mJ for X (80 kGy)‐warm respectively. The Izod impact strength of Vitelene® amounted to 81 kJ/m2, that of X (80 kGy)‐warm to 82 kJ/m2. Crystallinity of both was 52%. The melt temperature of Vitelene® was 140 °C, that of X (80 kGy)‐warm 139°C. In conclusion, using the same irradiation temperature (100 °C) and dose (80 kGy), the different radiation sources e‐beam and X‐rays resulted in equivalent thermal and mechanical properties.

    更新日期:2020-01-06
  • Multilayers of poly(ethyleneimine)/poly(acrylic acid) coatings on Ti6Al4V acting as lubricated polymer‐bearing interface
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-06
    Yaling Deng; Jianjun Sun; Xingya Ni; Dangsheng Xiong

    To achieve an efficient lubricated interface on titanium alloy (Ti6Al4V) alloy, polyelectrolyte multilayer (PEM) polymer coatings, based on poly(ethyleneimine)/poly(acrylic acid) (PEI/PAA), were fabricated on the surface of Ti6Al4V alloy substrates using the layer‐by‐layer (LbL) assembly technique. Their composition and morphology were confirmed by Fourier‐transform infrared/attenuated total reflectance (FTIR/ATR) spectroscopy, X‐ray photoelectron spectroscopy, and scanning electron microscopy. The tribological properties were investigated by a ball‐on‐disk rotating tribometer using deionized water, saline, and calf serum. The results exhibit that (PEI/PAA)*n coatings have the internal cross‐linked network and porous structure on the surface. The surface of PEI/PAA coatings‐modified Ti6Al4V shows the sufficient wettability. The polymer‐bearing interface of (PEI/PAA)*10 exhibits a low friction coefficient, 0.059, for 2 hr, and represents an 88% decline compared with bare Ti6Al4V. Moreover, the wear track on the polymer‐bearing interface is superlow. There is no obvious wear volume, which indicates effective wear resistance. The hydrated layer, the cross‐linked network structure, and the porous structure of PEM coatings are the main factors for efficient tribological properties. The multilayer PEI/PAA coating shows the potential uses of developing the lubricated‐bearing interface on Ti6Al4V alloy.

    更新日期:2020-01-06
  • An effective dual‐factor modified 3D‐printed PCL scaffold for bone defect repair
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-06
    Yan Li; Qian Li; Hongming Li; Xiao Xu; Xiaoming Fu; Jijia Pan; Hui Wang; Jerry Ying Hsi Fuh; Yanjie Bai; Shicheng Wei

    Numerous bioactive molecules produced in cells are involved in the process of bone formation. We consider that appropriate, simultaneous application of two types of bioactive molecules would accelerate the regeneration of tissues and organs. Therefore, we combined aspirin‐loaded liposomes (Asp@Lipo) and bone forming peptide‐1 (BFP‐1) on three dimensional‐printed polycaprolactone (PCL) scaffold and determined whether this system improved bone regeneration outcomes. in vitro experiments indicated that Asp@Lipo/BFP‐1at a 3:7 ratio was the best option for enhancing the osteogenic efficiency of human mesenchymal stem cells (hMSCs). This was confirmed in an in vivo cranial defect animal model. In addition, RNA‐Seq was applied for preliminarily exploration of the mechanism of action of this composite scaffold system, and the results suggested that it mainly improved bone regeneration via the PI3K/AKT signaling pathway. This approach will have potential for application in bone tissue engineering and regenerative medicine.

    更新日期:2020-01-06
  • Nanofibrous antibiotic‐eluting matrices: Biocompatibility studies in a rat model
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-04-23
    Patrícia C. Passos; Juliana Moro; Raquel Cristine Silva Barcelos; Higor Z. Da Rosa; Luciana T. Vey; Marilise Escobar Bürguer; Roberto M. Maciel; Cristiane C. Danesi; Paul C. Edwards; Marco C. Bottino; Karla Z. Kantorski

    This study evaluated the biocompatibility of degradable polydioxanone (PDS) electrospun drug delivery systems (hereafter referred as matrices) containing metronidazole (MET) or ciprofloxacin (CIP) after subcutaneous implantation in rats. Sixty adult male rats were randomized into six groups: SHAM (sham surgery); PDS (antibiotic‐free matrix); 1MET (one 25 wt% MET matrix); 1CIP (one 25 wt% CIP matrix); 2MET (two 25 wt% MET matrices); and 2CIP (two 25 wt% CIP matrices). At 3 and 30 days, animals were assessed for inflammatory cell response (ICR), collagen fibers degradation, and oxidative profile (reactive oxygen species [ROS]; lipid peroxidation [LP]; and protein carbonyl [PC]). At 3 days, percentages of no/discrete ICR were 100, 93.3, 86.7, 76.7, 50, and 66.6 for SHAM, PDS, 1MET, 1CIP, 2MET, and 2CIP, respectively. At 30 days, percentages of no/discrete ICR were 100% for SHAM, PDS, 1MET, and 1CIP and 93.3% for 2MET and 2CIP. Between 3 and 30 days, SHAM, 1CIP, and 2CIP produced collagen, while 1MET and 2MET were unchanged. At 30 days, the collagen fiber means percentages for SHAM, PDS, 1MET, 1CIP, 2MET, and 2CIP were 63.7, 60.7, 56.6, 62.6, 51.8, and 61.7, respectively. Antibiotic‐eluting matrices showed similar or better oxidative behavior when compared to PDS, except for CIP‐eluting matrices, which showed higher levels of PC compared to SHAM or PDS at 30 days. Collectively, our findings indicate that antibiotic‐eluting matrices may be an attractive biocompatible drug delivery system to fight periodontopathogens. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B, 2019.

    更新日期:2020-01-06
  • A foldable manipulator with tunable stiffness based on braided structure
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-04-22
    Zufeng Shang; Jiayao Ma; Zhong You; Shuxin Wang

    Minimally invasive surgery (MIS) has recently seen a surge in clinical applications due to its potential benefits over open surgery. In MIS, a long manipulator is placed through a tortuous human orifice to create a channel for surgical tools and provide support when they are operated. Currently the relative large profile and low stiffness of the manipulators limit the effectiveness and accuracy of MIS. Here we propose a new foldable manipulator with tunable stiffness. The manipulator takes a braided skeleton to enable radial folding, whereas membrane is used to seal the skeleton so as to adjust stiffness through creating negative pressure. We demonstrated experimentally, numerically, and analytically that, a flexible and a rigid state were obtained, and the ratio of bending stiffness in the rigid state to that in the flexible state reached 6.85. In addition, the manipulator achieved a radial folding ratio of 1.95. The proposed manipulator shows great potential in the design of surgical robots for MIS. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B, 2019.

    更新日期:2020-01-06
  • Polyglycolic acid‐collagen tube combined with collagen‐binding basic fibroblast growth factor accelerates gait recovery in a rat sciatic nerve critical‐size defect model
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-04-23
    Hisako Fujimaki; Kentaro Uchida; Gen Inoue; Osamu Matsushita; Noriko Nemoto; Masayuki Miyagi; Kazuhide Inage; Shotaro Takano; Sumihisa Orita; Seiji Ohtori; Keisuke Tanaka; Hiroyuki Sekiguchi; Masashi Takaso

    Several nerve conduits have been investigated for their potential as alternative sources of autografts for bridging neural gaps. However, autologous nerve transplants remain the most effective for nerve repair. We examined clinically approved nerve conduits containing collagen and polyglycolic acid (PGA‐c) combined with collagen‐binding basic fibroblast growth factor (bFGF) containing a polycystic kidney disease (PKD) domain and collagen binding domain (CBD) (bFGF‐PKD‐CBD) in a rat 15‐mm sciatic nerve critical‐size defect model. The treatment groups were: PGA‐c immersed in phosphate‐buffered saline (PBS) (PGA‐c/PBS group), bFGF (PGA‐c/bFGF group), or bFGF‐PKD‐CBD (PGA‐c/bFGF‐PKD‐CBD group), and no treatment (Defect group). Gait and histological analyses were performed. Four weeks after treatment, the recovery rate of the paw print area was significantly greater in the PGA‐c/bFGFPKD‐CBD group than the PGA‐c/PBS and PGA‐c/bFGF groups. Mean intensity of paw prints was significantly greater in the PGA‐c/bFGF‐PKD‐CBD group than the PGA‐c/PBS and Defect groups. Swing time was significantly greater in the PGA‐c/PBS, PGA‐c/bFGF, and PGA‐c/bFGF‐PKD‐CBD groups than the Defect group. At 8 weeks, all three parameters were significantly greater in the PGA‐c/PBS, PGA‐c/bFGF, and PGA‐c/bFGF‐PKD‐CBD groups than the Defect group. Regenerated myelinated fibers were observed in 7/8 (87.5%) rats in the PGA‐c/bFGF‐PKD‐CBD group after 8 weeks, and in 1/8 (12.5%) and 3/8 (37.5%) rats in the PGA‐c/PBS and PGA‐c/bFGF groups, respectively. PGA‐c/bFGF‐PKD‐CBD composites may be promising biomaterials for promoting functional recovery of long‐distance peripheral nerve defects in clinical practice.

    更新日期:2020-01-06
  • Effective control of biofilms by photothermal therapy using a gold nanorod hydrogel
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-04-30
    Carlos Bermúdez‐Jiménez; Nereyda Niño‐Martínez; Nuria Patiño‐Marín; Fidel Martínez‐Gutiérrez; Facundo Ruiz; Horacio Bach; Gabriel Martínez‐Castañón

    Biofilms are matrices synthesized by bacteria containing polysaccharides, DNA, and proteins. The development of biofilms in infectious processes can induce a chronic inflammatory response that may progress to the destruction of tissues. The treatment of biofilms is difficult because they serve as a bacterial mechanism of defense and high doses of antibiotics are necessary to treat these infections with limited positive results. It has been demonstrated that photothermal therapy using gold nanorods (AuNRs) is an attractive treatment because of its anti‐biofilm activity. The purpose of this work was to generate a novel chitosan‐based hydrogel embedded with AuNRs to evaluate its anti‐biofilm activity. AuNRs were synthesized by the seed‐mediated growth method and mixed with the chitosan‐based hydrogel. Hydrogels were characterized and tested against two bacterial strains by irradiating the produced biofilm in the presence of the nanoformulation with a laser adjusted at the near infrared spectrum. In addition, the safety of the nanoformulation was assessed with normal human gingival fibroblasts. Results showed that a significant bacterial killing was measured when biofilms were exposed to an increase of 10°C for a short time of 2 min. Moreover, no cytotoxicity was measured when normal gingival fibroblasts were exposed to the nanoformulation using the bactericidal conditions. The development of the reported formulation can be used as a direct application to treat periodontal diseases or biofilm‐produced bacteria that colonize the oral cavity.

    更新日期:2020-01-06
  • Mathematical predictions of oxygen availability in micro‐ and macro‐encapsulated human and porcine pancreatic islets
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-04-23
    Rui Cao; Efstathios Avgoustiniatos; Klearchos Papas; Paul de Vos; Jonathan R. T. Lakey

    Optimal function of immunoisolated islets requires adequate supply of oxygen to metabolically active insulin producing beta‐cells. Using mathematical modeling, we investigated the influence of the pO2 on islet insulin secretory capacity and evaluated conditions that could lead to the development of tissue anoxia, modeled for a 300 μm islet in a 500 μm microcapsule or a 500 μm planar, slab‐shaped macrocapsule. The pO2 was used to assess the part of islets that contributed to insulin secretion. Assuming a 500 μm macrocapsule with a 300 μm islet, with oxygen consumption rate (OCR) of 100–300 nmol min−1 mg−1 DNA, islets did not develop any necrotic core. The nonfunctional zone (with no insulin secretion if pO2 < 0.1 mmHg) was 0.3% for human islets (OCR ~100 nmol/min/mg DNA) and 35% for porcine islets (OCR ~300 nmol/min/mg DNA). The OCR of the islet preparation is profoundly affected by islet size, with optimal size of <250 μm in diameter (human) or <150 μm (porcine). Our data suggest that microcapsules afford superior oxygen delivery to encapsulated islets than macrocapsules, and optimal islet function can be achieved by encapsulating multiple, small (<150 μm) islets with OCR of ~100 nmol min−1 mg−1 DNA (human islets) or ~200 nmol min−1 mg−1 DNA (porcine islets).

    更新日期:2020-01-06
  • Effective delivery of mitomycin‐C and meloxicam by double‐layer electrospun membranes for the prevention of epidural adhesions
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-04-24
    Rui Shi; Yuelong Huang; Jingshuang Zhang; Chengai Wu; Min Gong; Wei Tian; Liqun Zhang

    Epidural adhesion between the spinal dura and the surrounding fibrous tissue often occurs post‐laminectomy, resulting in clinical symptoms such as nerve compression and severe pain. In this study, we report a drug‐loaded double‐layered electrospun nanofiber membrane to prevent the occurrence of epidural adhesion. The nanofibers in both layers are made of a mixture of polycaprolactone (PCL) and chitosan (CS) but at different weight ratios. The bottom layer contacting to the spinal dura is loaded with meloxicam (MX) to prevent inflammation. The top layer that contacts to the fibrous tissue is doped with mitomycin‐C (MMC) to inhibit the synthesis of DNA and collagen. The two types of drugs are released from the double‐layered membrane within about 12 days. Meanwhile, the membrane can inhibit fibroblasts proliferation in vitro while show no cytotoxicity. In a rabbit laminectomy model, the double‐layered membrane can effectively prevent the epidural adhesion formation based on the adhesion scores, histological and biochemical evaluations. The combination release of MX and MMC can signally reduce the inflammation reaction and collagen I/III expression relative to the case with the membranes loaded with only either one type of the drugs. This approach offers new progresses in constructing dual drug delivery system and provides innovative barrier strategy in inhibiting epidural adhesion post‐laminectomy.

    更新日期:2020-01-06
  • In vivo resorption of injectable apatitic calcium phosphate cements: Critical role of the intergranular microstructure
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-04-29
    Myriam Le Ferrec; Charlotte Mellier; Francois‐Xavier Lefèvre; Florian Boukhechba; Pascal Janvier; Gilles Montavon; Jean‐Michel Bouler; Olivier Gauthier; Bruno Bujoli

    The in vivo resorption rate of two injectable apatitic calcium phosphate cements used in clinics (Graftys® HBS and NORIAN®) was compared, using a good laboratory practice (GLP) study based on an animal model of critical‐sized bone defect. To rationalize the markedly different biological properties observed for both cements, key physical features were investigated, including permeability and water‐accessible porosity, total porosity measured by mercury intrusion and gravimetry, and microstructure. Due to a different concept for creating porosity between the two cements investigated in this study, a markedly different microstructural arrangement of apatite crystals was observed in the intergranular space, which was found to significantly influence both the mechanical strength and in vivo degradation of the two calcium phosphate cements.

    更新日期:2020-01-06
  • Composition control in biphasic silicate microspheres on stimulating new bone regeneration and repair of osteoporotic femoral bone defect
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-04-29
    Edem P. Ghamor‐Amegavi; Xianyan Yang; Jiandi Qiu; Lijun Xie; Zhijun Pan; Juncheng Wang; Xiangfeng Zhang; Xiurong Ke; Tengfei Zhao; Lei Zhang; Zhongru Gou

    Application of bioactive materials as synthetic bone graft substitutes in regenerative medicine has seen great evolution over the past decades in treating challengeable bone defects. However, balancing the preparation conditions and biological performances of inorganic biomaterials remain a great challenge, especially when there is lack of biomaterial design on how to control component distribution and how pathological bone responds to the biomaterial stimulations and osteogenesis. Here, our objective is to develop yolk‐shell Ca‐silicate microspheres and to investigate the potential biological performances to overcome the limitations in repair of osteoporotic bone defects. The introduction of β‐calcium silicate (CaSiO3) or mesoporous bioactive glass (MBG) into self‐curing β‐dicalcium silicate (Ca2SiO4) cement shell to form spherical granules (CaSiO3@Ca2SiO4, MBG@Ca2SiO4) was to retain the physicochemical property and/or microstructure of each component for optimizing bioactive ion release that could maximize osteostimulation in osteoporosis. We report a scalable shape‐controlled mild fabrication protocol to yield the yolk‐shell granules, endowing to different phases in yolk layer and interconnected macropore networks in the closely packed granule scaffolds. This unique heterostructure preparation is governed by coaxially aligned bilayer nozzle, inorganic powders and biocompatible binders. Extensive in vitro and in vivo evaluation showed that the CaSiO3@Ca2SiO4 and MBG@Ca2SiO4 granules exhibited many superior properties such as controllable ion release, improved biodegradation and enhanced osteogenic capability in comparison with the pure Ca2SiO4@Ca2SiO4, thereby opening new mild‐condition approach in fabricating osteogenesis‐tailored silicate biomaterials for bone regenerative medicine, especially for efficient reconstruction of challenging pathological bone defects.

    更新日期:2020-01-06
  • Enhanced bone formation onto the bone surface using a hydroxyapatite/collagen bone‐like nanocomposite
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-04-30
    Taizo Hiratsuka; Masayoshi Uezono; Kazuo Takakuda; Masanori Kikuchi; Sho Oshima; Taira Sato; Shoichi Suzuki; Keiji Moriyama

    The process of bone formation onto the bone surface using a hydroxyapatite/collagen bone‐like nanocomposite (HAp/Col) was investigated. Immersion tests were performed to evaluate the impact of pH on the degradation of the specimens in an aqueous environment. The specimens were soaked in aqueous solutions of pH 4.0, 5.0, and 7.0. Using standardized images, the top‐view areas of the specimens were measured. Animal experiments were performed to investigate the bone formation process onto the bone surface. The specimens were placed under the rat calvarial periosteum, and μCT image analysis and histological observation were performed on samples harvested on postoperative Days 3, 5, and 7. In all experiments, β‐tricalciumphosphate (β‐TCP) was adopted as the control. HAp/Col turned to gel in acidic environments below pH 5.0. In contrast to the β‐TCP, the HAp/Col specimens placed under the periosteum expanded and attained a hollow structure with a gel‐filled center, accompanied by larger volume of new bone and appearance of TRAP‐positive multinucleated cells on postoperative Day 5. Therefore, HAp/Col can enhance bone formation onto the bone surface via induction of TRAP‐positive multinucleated cells, and may have clinical applications.

    更新日期:2020-01-06
  • A new era for sterilization based on supercritical CO2 technology
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-27
    Nilza Ribeiro; Gonçalo C. Soares; Víctor Santos‐Rosales; Angel Concheiro; Carmen Alvarez‐Lorenzo; Carlos A. García‐González; Ana L. Oliveira

    The increasing complexity in morphology and composition of modern biomedical materials (e.g., soft and hard biological tissues, synthetic and natural‐based scaffolds, technical textiles) and the high sensitivity to the processing environment requires the development of innovative but benign technologies for processing and treatment. This scenario is particularly applicable where current conventional techniques (steam/dry heat, ethylene oxide, and gamma irradiation) may not be able to preserve the functionality and integrity of the treated material. Sterilization using supercritical carbon dioxide emerges as a green and sustainable technology able to reach the sterility levels required by regulation without altering the original properties of even highly sensitive materials. In this review article, an updated survey of experimental protocols based on supercritical sterilization and of the efficacy results sorted by microbial strains and treated materials was carried out. The application of the supercritical sterilization process in materials used for biomedical, pharmaceutical, and food applications is assessed. The opportunity of supercritical sterilization of not only replace the above mentioned conventional techniques, but also of reach unmet needs for sterilization in highly sensitive materials (e.g., single‐use medical devices, the next‐generation biomaterials, and medical devices and graft tissues) is herein unveiled.

    更新日期:2020-01-06
  • Synthesis and assessment of metallic ion migration through a novel calcium carbonate coating for biomedical implants
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-06
    Le Thi Bang; Luimar C. Filho; Håkan Engqvist; Wei Xia; Cecilia Persson

    Titanium (Ti) implants are commonly regarded as well accepted by the body. However, metal ion release is still a cause for concern. A small decrease in pH, which can be caused by inflammation, may produce a large increase in the corrosion rate of Ti implants. Coating the alloy with a buffer layer could have a significant protective effect. In this study, a calcium carbonate coating was developed on commercially pure Ti and a Ti–6Al–4V alloy through a hydrothermal treatment of previously NaOH‐treated surfaces in calcium‐citric acid chelate complexes. The results showed that a superstructured calcite coating layer formed on the Ti substrate after treatment at 170°C for 3 hr. The coating was approx. 1 μm thick and covered the substrate surface uniformly. When prolonging the hydrothermal treatment from 5 hr to 24 hr, the rhombohedral structure of calcite was observed in addition to the superstructure of calcite. Dissolution test results showed no significant differences in solution pH between the coated‐ and un‐coated samples. However, the CaCO3 coating reduced by approx. 2–5 times the Ti and V ion release from the substrate as compared to the uncoated material, at pH 4. CaCO3 and hydroxyapatite (HA) coatings gave nonsignificant effects at neutral pH although the HA coating showed a trend for better results at the longer time points. The reduction in metal ion release from the substrate and the buffering ability of the CaCO3 coating encourage further studies on this coating for clinical applications.

    更新日期:2020-01-06
  • Enhanced fully cellulose based forward and reverse blood typing assay
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-07
    Jasmina Casals‐Terré; Josep Farré‐Lladós; Joan A. López; Teresa Vidal; Maria Blanca Roncero

    This study presents an enhanced paper‐based analytical device (PAD) for forward and reverse group blood typing. The proposed PAD uses a novel methodology, which provides highly reliable results on a fully cellulose based device. The PAD was printed on different cellulose substrates. These substrates were made of different cellulose fibers (sisal and eucalyptus), different grammages, refining steps, and wet additive content. Best parameters were chosen to achieve high reliability on both forward and reverse blood typing. The substrates were patterned with five hydrophilic channels and two hydrophobic areas. For reverse blood typing, the hemoagglutination reaction took place on the hydrophobic surface of the paper before being transferred to the paper web, where together with the forward blood typing tests were all washed with saline solution to read the results by elution. This device allows direct read‐out of results; the stains show were agglutination happens. Different blood types were in full agreement between the reverse and forward method and in agreement with traditional methods. The time and simplicity of this methodology confirmed its utility.

    更新日期:2020-01-06
  • Visible light‐induced photocatalytic and antibacterial activity of N‐doped TiO2
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-14
    Misato Iwatsu; Hiroyasu Kanetaka; Takayuki Mokudai; Toru Ogawa; Masakazu Kawashita; Keiichi Sasaki

    Previous reports of some studies have described that nitrogen (N)‐doped titanium dioxide (TiO2) exhibits photocatalytic antibacterial activity under visible light irradiation and that reactive oxygen species (ROS) is involved in its activity. For prevention and treatment of peri‐implantitis, an inflammatory lesion caused by the bacterial infection of plaque adhering to the circumference of an implant, we considered that applying N‐doped TiO2 to dental implant surfaces can be effective. For this study, we aimed at evaluating visible light‐induced antibacterial activity of titanium (Ti) treated with NaOH and hot water, and subsequently heated in an ammonia (NH3) gas atmosphere at 500°C for 3 hr to quantify the generated amount of ROS available for antibacterial activity. N‐doped anatase‐type titania (TiO2‐xNx) is formed on the Ti substrate surface. Under visible light, markedly more hydroxyl radicals were generated with a nitrogen‐doped titanium dioxide plate than with a pure titanium plate. Hydrogen peroxide exhibited the same tendency. Furthermore, it showed visible light‐induced antibacterial effects over Escherichia coli. Results demonstrate that N‐doped TiO2 can be useful as a dental implant surface with low risk of postoperative infection when using visible light irradiation.

    更新日期:2020-01-06
  • Introduction of a novel guided bone regeneration memory shape based device
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-08
    Osama Zakaria; Marwa Madi; Shohei Kasugai

    Bone regeneration by periosteal distraction has been reported in numerous animal studies; however, the main disadvantages of this technique are poor bone quality and soft tissue invasion in the distracted space. The purpose of this study was to evaluate a novel shape memory‐based device to promote bone regeneration in a large, secluded growth space in a rabbit model. Twenty rabbits were divided into two groups. In the first group (n = 10), a device composed of silicone sheets and nitinol strips was inserted subperiosteally in the calvarial area. In the second group (n = 10), only silicone sheets were inserted in the calvarial area. Each group was further divided in half: five animals were sacrificed at 8 weeks postoperatively, and the other five were sacrificed at 16 weeks postoperatively. In the study group, the new device vertically expanded the overlying soft tissue 4 mm above the original bone and created a secluded space; the newly generated bone maximum height median ranged between 2.7 mm in 8 weeks group and 2.6 mm in 16 weeks group. In the control group, a very thin rim of bone was generated below the flat silicone sheets on top of the original bone. Maximum bone heights median ranged from 0.37 mm in 8 weeks group to 0.32 mm in 16 weeks group. The device was proven to be effective at vertically augmenting bone by applying the guided bone regeneration and soft tissue expansion procedures simultaneously. This device may pave the way for a new generation of smart guided bone regeneration membranes that can remember the original dimensions of resorbed bone areas.

    更新日期:2020-01-06
  • Ex vivo pregnant‐like tissue model to assess injectable hydrogel for preterm birth prevention
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-09
    Nicole R. Raia; Stephanie L. Bakaysa; Chiara E. Ghezzi; Michael D. House; David L. Kaplan

    Cervical insufficiency (CI) is an important cause of preterm birth, which leads to severe newborn complications. Standard treatment for CI is cerclage, which has variable success rates, resulting in a clinical need for alternative treatments. Our objective was to develop an ex vivo model of softened cervical tissue to study an injectable silk‐based hydrogel as a novel alternative treatment for CI. Cervical tissue from nonpregnant women was enzymatically treated and characterized to determine tissue hydration, collagen organization, and mechanical properties via unconfined compression. Enzymatic treatment led to an 86 ± 7.9% decrease in modulus, which correlated to a decrease in collagen organization as observed by differences in collagen birefringence. The softened tissue was injected with a crosslinked silk‐hyaluronic acid composite hydrogel. After injection, the mechanical properties and volume increase of the hydrogel‐treated tissue were measured resulting in a 54 ± 16% volume increase with minimal effect on tissue mechanical properties. In addition, cervical fibroblasts on silk‐hyaluronic acid hydrogels remained viable and exhibited increased proliferation and metabolic activity over 5 days. Overall, this study developed an ex vivo pregnant‐like human tissue model to assess cervical augmentation and showed the potential of silk‐based hydrogels as an alternative treatment for cervical insufficiency.

    更新日期:2020-01-06
  • Comparing the release of erythromycin and vancomycin from calcium polyphosphate hydrogel using different drug loading methods
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-09
    Yasaman Chehreghanianzabi; Rajib Barua; Tong Shi; Sally Yurgelevic; Gregory Auner; David C. Markel; Weiping Ren

    Calcium polyphosphate (CPP) hydrogel is used to load erythromycin (EM) and vancomycin (VCM) by means of two loading methods: they are either added directly to the formed CPP hydrogel (Gel Mixture method) or mixed with CPP powders, followed by the formation of CPP‐antibiotic hydrogel (Powder Mixture method). The release of loaded antibiotics from CPP hydrogel is measured up to 48 hr. Compared to Powder Mixture method, Gel Mixture method significantly reduced the burst release of embedded antibiotics. A significant change in CPP hydrogel Raman characteristic peaks is observed only in Gel Mixture method, indicating a close interaction between embedded antibiotics with CPP hydrogel matrix. In contrast, a similarity between characteristic peaks of CPP hydrogel and Powder Mixture method shows that antibiotic incorporation does not interfere with CPP gel formation, resulting in no ionic interaction between antibiotic and polyphosphate chains. Rheometer analysis further confirms that the hydrophobic nature of EM impacts the viscoelastic properties of CPP hydrogel, whereas the hydrophilic VCM exhibits a higher loading efficiency. The potential application of CPP hydrogel as a ceramic matrix for sustained drug release warrants further investigation.

    更新日期:2020-01-06
  • Antibacterial activity of copper‐bearing 316L stainless steel for the prevention of implant‐related infection
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-09
    Yifu Zhuang; Shuyuan Zhang; Ke Yang; Ling Ren; Kerong Dai

    Implant‐related infection (IRI) is a devastating complication in orthopedic procedures. Traditional materials used in orthopedics are susceptible to bacterial infection. In this study, we developed a copper‐bearing 316L stainless steel (316L‐Cu SS) for the prevention of IRI. This 316L‐Cu SS allowed stable and continuous release of copper ions with a rate of 5.079 ng/cm2/day. Compared with 316L stainless steel (316L SS), 316L‐Cu SS exhibited a broad‐spectrum antibacterial effect against Staphylococcus aureus, Escherichia coli, and Staphylococcus epidermidis with the bacterial reduction percentages of 95.2, 94.8, and 94.1%, respectively. The antibiofilm activity was confirmed by crystal violet assay, scanning electron microscopy, and confocal laser scanning microscopy. The in vivo antibacterial performance was tested on a rat model. When nails were treated with a low concentration of bacteria, 316L SS group exhibit a bone infection with a radiographic score of 8.9 ± 1.1 and a histological score of 10.4 ± 1.0, which were higher than 316L‐Cu SS group (1.2 ± 0.2 and 0.9 ± 0.2), indicating IRI was reduced by 316L‐Cu SS. When nails were treated with a high concentration of bacteria, IRI was also alleviated by 316L‐Cu SS. Together, these results demonstrated that 316L‐Cu SS is a promising material for preventing IRI.

    更新日期:2020-01-06
  • Tethered‐liquid omniphobic surface coating reduces surface thrombogenicity, delays clot formation and decreases clot strength ex vivo
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-08
    Teryn R. Roberts; Daniel C. Leslie; Andrew P. Cap; Leopoldo C. Cancio; Andriy I. Batchinsky

    Hemocompatible materials for extracorporeal life support (ECLS) technology are investigated to mitigate thrombotic complications associated with this therapy. A promising solution is an omniphobic bilayer coating, tethered liquid perfluorocarbon (TLP), which utilizes an immobilized tether to anchor a mobile, liquid surface lubricant that prevents adhesion of blood components to the substrate. In this study, we investigated the effects of TLP on real‐time clot formation using thromboelastography (TEG). TLP was applied to TEG cups, utilizing perfluorodecalin (PFD) or FluorLube63 as the liquid layer, and compared to uncoated cups. Human blood (n = 10) was added to cups; and TEG parameters (R, K, α‐angle, MA, LY30, LY60) and adherent thrombus weight were assessed. TLP decreased clot amplification (α‐angle), clot strength (MA), and adherent clot weight (p < .0001). These effects were greater with FluorLube63 versus PFD (α‐angle p < .0001; MA p = .0019; clot weight p < .0001). Reaction time (R) was longer in TLP‐coated cups versus control cups with liquid lubricant added (p = .0377). Percent fibrinolysis (LY30 and LY60) was greater in the TLP versus controls at LY30 (p < .0001), and in FluoroLube63 versus controls at LY60 (p = .0021). TLP significantly altered clot formation, exerting antithrombogenic effects. This reduction in surface thrombogenicity supports TLP as a candidate for improved biocompatibility of ECLS materials, pending further validation with exposure to shear stress.

    更新日期:2020-01-06
  • Bioadhesive and biodissolvable hydrogels consisting of water‐swellable poly(acrylic acid)/poly(vinylpyrrolidone) complexes
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-08
    Tomoko Ito; Naoki Otani; Kazuya Fujii; Kentaro Mori; Masazumi Eriguchi; Yoshiyuki Koyama

    Films that can form bioadhesive hydrogels on wet biotissues absorbing blood or body fluids are useful for medical devices such as hemostats, adhesion barriers, wound dressings, and drug release devices. We focused on a hydrogen‐bonding polymer complex consisting of poly(acrylic acid) (PAA) and poly(vinylpyrrolidone) (PVP). PAA is known as a tissue‐adhesive polymer. However, simple mixing of aqueous PAA and PVP solutions resulted in the formation of an insoluble nonadhesive precipitate. We developed a novel solid/solution interface complexation method to afford a PAA/PVP complex that forms a strongly bioadhesive hydrogel with low cytotoxicity. The complex hydrogel can be slowly dissociated and dissolved in the body. The formation of the complexes as well as their swelling and degradation behavior depended strongly on the molecular weights and cross‐linking densities of the component polymers. When the complex film was applied to a clipped incised jugular vein of a rat, it immediately formed a hydrogel and closed the incision. After removal of the clip, blood flowed through the vessel without any leakage. Application of the complex film to the surface of an incised mouse liver resulted in firm adhesion and the hemorrhage was effectively stopped. Such bioadhesive and biodissolvable materials consisting of low‐toxicity synthetic polymers have high potential for implantable medical devices.

    更新日期:2020-01-06
  • Fourier transform infrared spectroscopic imaging of wear and corrosion products within joint capsule tissue from total hip replacements patients
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-17
    Songyun Liu; Deborah J. Hall; Stephanie M. McCarthy; Joshua J. Jacobs; Robert M. Urban; Robin Pourzal

    Implant debris generated by wear and corrosion is a prominent cause of joint replacement failure. This study utilized Fourier transform infrared spectroscopic imaging (FTIR‐I) to gain a better understanding of the chemical structure of implant debris and its impact on the surrounding biological environment. Therefore, retrieved joint capsule tissue from five total hip replacement patients was analyzed. All five cases presented different implant designs and histopathological patterns. All tissue samples were formalin‐fixed and paraffin‐embedded. Unstained, 5 μm thick sections were prepared. The unstained sections were placed on BaF2 windows and deparaffinized with xylene prior to analysis. FTIR‐I data were collected at a spectral resolution of 4 cm−1 using an Agilent Cary 670 spectrometer coupled with Cary 620 FTIR microscope. The results of study demonstrated that FTIR‐I is a powerful tool that can be used complimentary to the existing histopathological evaluation of tissue. FTIR‐I was able to distinguish areas with different cell types (macrophages, lymphocytes). Small, but distinct differences could be detected depending on the state of cells (viable, necrotic) and depending on what type of debris was present (polyethylene [PE], suture material, and metal oxides). Although, metal oxides were mainly below the measurable range of FTIR‐I, the infrared spectra of tissues exhibited noticeable difference in their presence. Tens of micrometer sized polyethylene particles could be easily imaged, but also accumulations of submicron particles could be detected within macrophages. FTIR‐I was also able to distinguish between PE debris, and other birefringent materials such as suture. Chromium‐phosphate particles originating from corrosion processes within modular taper junctions of hip implants could be identified and easily distinguished from other phosphorous materials such as bone. In conclusion, this study successfully demonstrated that FTIR‐I is a useful tool that can image and determine the biochemical information of retrieved tissue samples over tens of square millimeters in a completely label free, nondestructive, and objective manner. The resulting chemical images provide a deeper understanding of the chemical nature of implant debris and their impact on chemical changes of the tissue within which they are embedded.

    更新日期:2020-01-06
  • Epidermal growth factor receptor genes are overexpressed within the periprosthetic soft‐tissue around percutaneous devices: A pilot study
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-10
    Sujee Jeyapalina; John S. Colombo; James P. Beck; Jayant P. Agarwal; Linda A. Schmidt; Kent N. Bachus

    Epidermal downgrowth around percutaneous devices produce sinus tracts, which then accumulate bacteria becoming foci of infection. This mode to failure is epidermal‐centric, and is accelerated by changes in the chemokines and cytokines of the underlying periprosthetic granulation tissue (GT). In order to more fully comprehend the mechanism of downgrowth, in this 28‐day study, percutaneous devices were placed in 10 Zucker diabetic fatty rats; 5 animals were induced with diabetes mellitus II (DM II) prior to the surgery and 5 animals served as a healthy, nondiabetic cohort. At necropsy, periprosthetic tissues were harvested, and underwent histological and polymerase chain reaction (PCR) studies. After isolating GTs from the surrounding tissue and extracting ribonucleic acids, PCR array and quantitative‐PCR (qPCR) analyses were carried‐out. The PCR array for 84 key wound‐healing associated genes showed a five‐fold or greater change in 31 genes in the GTs of healthy animals compared to uninjured healthy typical skin tissues. Eighteen genes were overexpressed and these included epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR). Thirteen genes were underexpressed. When GTs of DM II animals were compared to healthy animals, there were 8 genes overexpressed and 25 genes underexpressed; under expressed genes included EGF and EGFR. The qPCR and immunohistochemistry data further validated these observations. Pathway analysis of genes up‐regulated 15‐fold or more indicated two, EGFR and interleukin‐10, centric clustering effects. It was concluded that EGFR could be a key player in exacerbating the epidermal downgrowth, and might be an effective target for preventing downgrowth.

    更新日期:2020-01-06
  • Indocyanine green based fluorescent polymeric nanoprobes for in vitro imaging
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-14
    Zeynep R. Ege; Aydin Akan; Faik N. Oktar; Chi C. Lin; Durdane S. Kuruca; Betul Karademir; Yesim M. Sahin; Gokce Erdemir; Oguzhan Gunduz

    Indocyanine green (ICG) provides an advantage in the imaging of deep tumors as it can reach deeper location without being absorbed in the upper layers of biological tissues in the wavelengths, which named “therapeutic window” in the tissue engineering. Unfortunately, rapid elimination and short‐term stability in aqueous media limited its use as a fluorescence probe for the early detection of cancerous tissue. In this study, stabilization of ICG was performed by encapsulating ICG molecules into the biodegradable polymer composited with poly(l‐lactic acid) and poly(ε‐caprolactone) via a simple one‐step multiaxial electrospinning method. Different types of coaxial and triaxial structure groups were performed and compared with single polymer only groups. Confocal microscopy was used to image the encapsulated ICG (1 mg/mL) within electrospun nanofibers and in vitro ICG uptake by MIA PaCa‐2 pancreatic cancer cells. Stability of encapsulated ICG is demonstrated by the in vitro sustainable release profile in PBS (pH = 4 and 7) up to 21 days. These results suggest the potential of the ability of internalization and accommodation of ICG into the pancreatic cell cytoplasm from in vitro implanted ICG‐encapsulated multiaxial nanofiber mats. ICG‐encapsulated multilayer nanofibers may be promising for the local sustained delivery system to eliminate loss of dosage caused by direct injection of ICG‐loaded nanoparticles in systemic administration.

    更新日期:2020-01-06
  • Hyaluronic acid hydrogel loaded by adipose stem cells enhances wound healing by modulating IL‐1β, TGF‐β1, and bFGF in burn wound model in rat
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-13
    Esmat Alemzadeh; Ahmad Oryan; Ali A. Mohammadi

    Application of hydrogels can be an effective technique in transferring the adipose‐derived stem cells (ASCs) to injured tissue and their protection from further complications. Besides, acellular dermal matrix (ADM) has successfully been used in treatment of wounds. In this study, a combination of hylauronic acid (HA) and ASCs (HA/ASCs) was applied on burn wounds and the injured area was then covered by an ADM dressing in a rat model (ADM‐HA/ASCs). Wound healing was evaluated by histopathological, histomorphometrical, molecular, biochemical, and scanning electron microscopy assessments on days 7, 14, and 28 post‐wounding. ADM‐HA/ASCs stimulated healing significantly more than the ADM‐HA and ADM treated wounds, as it led to reduced inflammation, and improved angiogenesis and enhanced granulation tissue formation. Expression of interleukin‐1β (IL‐1β) and transforming growth factor‐β1 (TGF‐β1) was lower in the ADM‐HA/ASCs treated wounds than the ADM‐HA and ADM groups, at the seventh post‐wounding day. ADM‐HA/ASCs also enhanced the expression level of TGF‐β1 mRNA at 14 day post‐wounding that was parallel to the experimental data from histological and biochemical assessments and confirmed the positive role of ASCs in repair of burn wounds. Additionally, increase in basic fibroblast growth factor (bFGF) expression and decreased TGF‐β1 level on the 28th post‐wounding day indicated the anti‐scarring activity of ASCs. HA loaded by adipose stem cells can represent a promising strategy in accelerating burn wound healing.

    更新日期:2020-01-06
  • A miniaturized piezoresistive flow sensor for real‐time monitoring of intravenous infusion
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-20
    Reza Hagihghi; Amir Razmjou; Yasin Orooji; Majid E. Warkiani; Mohsen Asadnia
    更新日期:2020-01-06
  • Biological acellular pericardial mesh regulated tissue integration and remodeling in a rat model of breast prosthetic implantation
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-05-15
    Roberta Bernardini; Dimitrios Varvaras; Federico D'Amico; Alessandra Bielli; Maria Giovanna Scioli; Filadelfo Coniglione; Piero Rossi; Oreste C. Buonomo; Giuseppe Petrella; Maurizio Mattei; Augusto Orlandi

    The use of biological meshes has proven beneficial in surgical restriction and periprosthetic capsular contracture following breast prosthetic‐reconstruction. Three different types (smooth, texturized, and polyurethane) of silicone round mini prostheses were implanted under rat skin with or without two different bovine acellular pericardial biological meshes (APMs, BioRipar, and Tutomesh). One hundred eighty‐six female rats were divided into 12 groups, sacrificed after 3, 6, and 24 weeks and tissue samples investigated by histology and immunohistochemistry. Implantation of both APMs, with or without prostheses, reduced capsular α‐SMA expression and CD3+ inflammatory cell infiltration, increasing capillary density and cell proliferation, with some differences. In particular, Tutomesh was associated with higher peri‐APM CD3+ inflammation, prosthetic capsular dermal α‐SMA expression and less CD31+ vessels and cell proliferation compared with BioRipar. None differences were observed in tissue integration and remodeling following the APM + prostheses implantation; the different prostheses did not influence tissue remodeling. The aim of our study was to investigate if/how the use of different APMs, with peculiar intrinsic characteristics, may influence tissue integration. The structure of APMs critically influenced tissue remodeling after implantation. Further studies are needed to develop new APMs able to optimize tissue integration and neoangiogenesis minimizing periprosthetic inflammation and fibrosis.

    更新日期:2020-01-06
  • Reactive oxygen/nitrogen species (ROS/RNS) and oxidative stress in arthroplasty
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2020-01-02
    Rita Hameister; Charanjit Kaur; Shaikali Thameem Dheen; Christoph H. Lohmann; Gurpal Singh

    The interplay between implant design, biomaterial characteristics, and the local microenvironment adjacent to the implant is of utmost importance for implant performance and success of the joint replacement surgery. Reactive oxygen and nitrogen species (ROS/RNS) are among the various factors affecting the host as well as the implant components. Excessive formation of ROS and RNS can lead to oxidative stress, a condition that is known to damage cells and tissues and also to affect signaling pathways. It may further compromise implant longevity by accelerating implant degradation, primarily through activation of inflammatory cells. In addition, wear products of metallic, ceramic, polyethylene, or bone cement origin may also generate oxidative stress themselves. This review outlines the generation of free radicals and oxidative stress in arthroplasty and provides a conceptual framework on its implications for soft tissue remodeling and bone resorption (osteolysis) as well as implant longevity. Key findings derived from cell culture studies, animal models, and patients' samples are presented. Strategies to control oxidative stress by implant design and antioxidants are explored and areas of controversy and challenges are highlighted. Finally, directions for future research are identified. A better understanding of the host‐implant interplay and the role of free radicals and oxidative stress will help to evaluate therapeutic approaches and will ultimately improve implant performance in arthroplasty.

    更新日期:2020-01-04
  • Evaluation of soft‐tissue response around laser microgrooved titanium percutaneous devices
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-30
    Divya R. L. Pawar; Sujee Jeyapalina; Kent N. Bachus

    Percutaneous devices are prone to epidermal downgrowth and sinus tract formation, which can serve as a nidus for bacterial colonization and increase the risk of peri‐prosthetic infection. A laser microgrooved topography has been shown to limit gingival epidermal downgrowth around dental implants. However, the efficacy of this laser microgrooved topography to limit epidermal downgrowth around nongingival percutaneous devices is yet to be investigated. In this study, devices with a porous‐coated subdermal component and a percutaneous post were designed and manufactured. The proximal 2 mm section of the percutaneous post were left smooth, or were textured with either a porous coating, or with the laser microgrooved topography. The smooth and porous topographies served as controls. The devices were tested in a hairless guinea pig back model, where 18 animals were randomly assigned into three groups, with each group receiving one implant type (n = 6/group). Four weeks postimplantation, the devices with surrounding soft‐tissues were harvested and processed for histological analyses. Results indicated that the laser microgrooved topography failed to prevent epidermal downgrowth (23 ± 4%) around percutaneous posts in this model. Furthermore, no significant differences (p = 0.70) in epidermal downgrowth were present between the three topographies, with all the groups exhibiting similar measures of downgrowth. Overall, these findings suggest that the laser microgrooved topography may not halt downgrowth around percutaneous devices for dermal applications.

    更新日期:2019-12-31
  • Current status and future outlook of nano‐based systems for burn wound management
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-30
    Morteza Abazari; Azadeh Ghaffari; Hamid Rashidzadeh; Safa Momeni badeleh; Yaser Maleki
    更新日期:2019-12-30
  • Structural characterization, mechanical, and electrochemical studies of hydroxyapatite‐titanium composite coating fabricated using electrophoretic deposition and reaction bonding process
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-30
    Hossein Maleki‐Ghaleh; Jafar Khalil‐Allafi; Nazila Horandghadim; Pardis Keikhosravani; Mir Ghasem Hosseini

    In the present work, hydroxyapatite (HA)‐titanium (Ti, 20 wt%) composite coating was coated on NiTi alloy substrate by EPD (electrophoretic deposition) process. Before applying the coating, the HA powder was composed with Ti powder using a ball milling process. Influence of the ball milling time on morphology and phase structure of HA‐Ti powder was evaluated using TEM and XRD analysis. After composing the HA particles with Ti, the HA‐Ti composite powders were coated on the NiTi substrate by the EPD process in an n‐butanol medium for 2 min, with the applied voltage of 60 V. XRD and SEM analysis were utilized to evaluate the phase analysis and morphology of the coatings. Mechanical and electrochemical characteristic of the coatings were also assessed using the micro‐indentation, micro‐scratch, and polarization tests, respectively. The results revealed that the milling process time had a significant influence on reaction bonds and optimum mixing time was 4 hr. Micro‐hardness of the HA‐Ti composite coating (304 HV) was substantially higher than the HA coating (72 HV). Also, as the HA coating was composed with Ti particles, the amount of force (in the micro‐scratch test) required for detaching the coating from the NiTi substrate increased from 7.1 to 17.8 N. The polarization results showed that the HA‐Ti composite coating had a higher electrochemical resistance compared with the HA coating. Corrosion resistance of the NiTi alloy coated with HA increased from 133 kΩ.cm2 to 2,720 kΩ.cm2 after composed with the Ti particles.

    更新日期:2019-12-30
  • Study on microstructure, microhardness, bioactivity, and biocompatibility of La2O3‐containing bioceramic coating doping SiO2 fabricated by laser cladding
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-28
    Qi Fu; Qibin Liu; Long Li; Xingmao Li; Huaizhang Gu; Bo Sheng; Bangcheng Yang

    To solve the lack of strength of calcium phosphate ceramic coatings in load‐bearing applications, gradient Ca‐P bioceramic coatings doped with La2O3 and SiO2 are fabricated by laser cladding on Ti‐6Al‐4 V. The effect of SiO2 on microstructure, microhardness, bioactivity, and biocompatibility of coatings was investigated. The experimental results illustrate that the coating doped with La2O3 and SiO2 has excellent metallurgical bonding. The XRD analysis confirms that the amount of hydroxyapatite and tricalcium phosphate in the coating reached maximum when doping amount of SiO2 is 10 wt %. SiO2‐doped coatings show a significantly higher bone‐like apatite precipitation after immersion in SBF than that of other coatings. in vitro experiment also shows that coating with 10 wt % SiO2 is more suitable for the attachment and proliferation of MG63 cells, indicating that coating with 10 wt % SiO2 exhibits best bioactivity and biocompatibility. These results suggest that the addition of SiO2 improves the bonding strength, bioactivity, and biocompatibility of coatings.

    更新日期:2019-12-29
  • Cytotoxicity and genotoxicity of DMABEE, a co‐photoinitiator of resin polymerization, on CHO‐K1 cells: Role of redox and carboxylesterase
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-27
    Hsiao‐Hua Chang; Wen‐Chih Shih; Yin‐Lin Wang; Yi‐Ling Tsai; Yi‐Jane Chen; Mei‐Chi Chang; Jiiang‐Huei Jeng

    The 4‐dimethylaminobenzoic acid ethyl ester (DMABEE) is an important co‐initiator for resin polymerization in dental resinous materials. As a radical forming chemical with high lipophilicity, the genotoxicity and cytotoxicity of DMABEE deserve prudent investigation. In this study, we found that DMABEE reduced the viability and proliferation of Chinese hamster ovary (CHO‐K1) cells in a dose‐dependent manner, and altered cell morphology at higher concentrations. G0/G1 cell cycle arrest was induced by DMABEE at 0.25–0.75 mM, and cell proportion of sub‐G0/G1 phase was significantly elevated at 1 mM while cell apoptosis was observed. Genotoxic effect was noted when cells were treated by 0.1 mM DMABEE, as revealed by increase of micronucleus formation. Reactive oxygen species overproduction was observed as cells treated with 0.75 and 1 mM, while elevation of intracellular glutathione was noticeable since 0.1 mM. Contrary to our expectation, pretreatment by N‐acetyl‐l‐cysteine enhanced the toxicity of DMABEE on CHO‐K1 cells. Catalase mildly reduced the toxic effect and carboxylesterase showed obvious ability to reverse the toxicity of DMABEE. These findings highlight the mechanism of DMABEE toxicity and provide clues for safety improvement of its application in clinical dental treatment.

    更新日期:2019-12-27
  • Workshop on the characterization of fiber‐based scaffolds: Challenges, progress, and future directions
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-27
    Lexi Garcia; Sherif Soliman; Michael P. Francis; Michael J. Yaszemski; Jayesh Doshi; Carl G. Simon; Rebecca Robinson‐Zeigler

    A critical component of many tissue‐engineered medical products (TEMPs) is the scaffold or biomaterial. The industry's understanding of scaffold properties and their influence on cell behavior has advanced, but our technical capability to reliably characterize scaffolds requires improvement, especially to enable large‐scale manufacturing. In response to the key findings from the 2013 ASTM International Workshop of Standards and Measurements for Tissue Engineering Scaffolds, the National Institute of Standards and Technology (NIST), ASTM International, BiofabUSA, and the Standards Coordinating Body (SCB) organized a workshop in 2018 titled, “Characterization of Fiber‐Based Scaffolds”. The goal was to convene a group of 40 key industry stakeholders to identify major roadblocks in measurements of fiber‐based scaffold properties. This report provides an overview of the findings from this collaborative workshop. The four major consensus findings were that (a) there is need for a documentary standard guide that would aid developers in the selection of test methods for characterizing fiber‐based scaffolds; (b) there is a need for a strategy to assess the quality of porosity and pore size measurements, which could potentially be ameliorated by the development of a reference material; (b) there are challenges with the lexicon used to describe and assess scaffolds; and (d) the vast array of product applications makes it challenging to identify consensus test methods. As a result of these findings, a working group was formed to develop an ASTM Standard Guide for Characterizing Fiber‐Based Constructs that will provide developers guidance on selecting measurements for characterizing fiber‐based scaffolds.

    更新日期:2019-12-27
  • Investigation of multiphasic 3D‐bioplotted scaffolds for site‐specific chondrogenic and osteogenic differentiation of human adipose‐derived stem cells for osteochondral tissue engineering applications
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-27
    Liliana F. Mellor; Rachel C. Nordberg; Pedro Huebner; Mahsa Mohiti‐Asli; Michael A. Taylor; William Efird; Julia T. Oxford; Jeffrey T. Spang; Rohan A. Shirwaiker; Elizabeth G. Loboa

    Osteoarthritis is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage and subchondral bone. The limited regenerative capacity of cartilage presents significant challenges when attempting to repair or reverse the effects of cartilage degradation. Tissue engineered medical products are a promising alternative to treat osteochondral degeneration due to their potential to integrate into the patient's existing tissue. The goal of this study was to create a scaffold that would induce site‐specific osteogenic and chondrogenic differentiation of human adipose‐derived stem cells (hASC) to generate a full osteochondral implant. Scaffolds were fabricated using 3D‐bioplotting of biodegradable polycraprolactone (PCL) with either β‐tricalcium phosphate (TCP) or decellularized bovine cartilage extracellular matrix (dECM) to drive site‐specific hASC osteogenesis and chondrogenesis, respectively. PCL‐dECM scaffolds demonstrated elevated matrix deposition and organization in scaffolds seeded with hASC as well as a reduction in collagen I gene expression. 3D‐bioplotted PCL scaffolds with 20% TCP demonstrated elevated calcium deposition, endogenous alkaline phosphatase activity, and osteopontin gene expression. Osteochondral scaffolds comprised of hASC‐seeded 3D‐bioplotted PCL‐TCP, electrospun PCL, and 3D‐bioplotted PCL‐dECM phases were evaluated and demonstrated site‐specific osteochondral tissue characteristics. This technique holds great promise as cartilage morbidity is minimized since autologous cartilage harvest is not required, tissue rejection is minimized via use of an abundant and accessible source of autologous stem cells, and biofabrication techniques allow for a precise, customizable methodology to rapidly produce the scaffold.

    更新日期:2019-12-27
  • Influence of liner offset and locking mechanism on fatigue durability in highly cross‐linked polyethylene total hip prostheses
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-26
    Kosuke Kamada; Yasuhito Takahashi; Toshiyuki Tateiwa; Takaaki Shishido; Toshinori Masaoka; Giuseppe Pezzotti; Kengo Yamamoto

    Highly cross‐linked, ultrahigh molecular weight polyethylene (HXLPE) acetabular liners are inherently associated to a risk of fatigue failure due to femoral neck impingement. Different thicknesses and designs employed with HXLPE liners greatly affect mechanical loading scenario. The purpose of this study was to clarify the influence of liner offset (lateralization) and locking mechanism (presence/absence of anti‐rotation tabs in the external surface) on fatigue durability in annealed and vitamin E‐blended HXLPE liners with a current commercial design. Each liner tested had six anti‐rotation tabs, which were engaged in the 6 of 12 recesses on the metal shell. The remaining six recesses had no direct contact with the liner, where HXLPE was mechanically unsupported by the metal backing. These mated and/or unmated rim regions in the offset (2, 3, 4‐mm lateralized) liners were exposed to severe neck impingement until crack propagation was identified. Phase volume percentages (crystalline, amorphous, and intermediate phase contents) of HXLPE liners were compared before and after impingement in order to interpret differences in impingement micromechanics associated with the rim design variations. Our results showed that the presence of unmated recesses served as a stress concentrator due to the formation of millimeter‐scale gaps between the liner and shell. Another potential design problem drawn from our study was liner offset associated with a small volume protruding above the metal rim. Therefore, surgeons should take special care in selecting locking designs and geometries especially when using HXLPE offset liners.

    更新日期:2019-12-27
  • Effect of multipurpose care solutions upon physical dimensions of silicone hydrogel contact lenses
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-26
    Stephanie M. Smith; Dongkai Zhu; David Pierre; Jeremy L. Gilbert; Joseph A. Chinn

    Interactions between contact lens multipurpose solution (MPS) components and the contact lenses with which they are used are both lens and solution dependent. As such, lens dimensional changes may arise after cleaning and immersion cycling in different lens care solutions over different time courses. In this study, the dimensional stability of five planned‐replacement silicone hydrogel lenses (lotrafilcon B, comfilcon A, senofilcon A, senofilcon C, and samfilcon A) over 30 cycles in three different MPSs (Biotrue, OPTI‐FREE Express, and OPTI‐FREE Puremoist) was evaluated. Measurements of diameter, sagittal depth, power, roundness, and center thickness were obtained prior to, during, and after 30 cycles of cleaning and storage. Diameters of all lenses increased when soaked in Express or Biotrue but held the International Standards Organization (ISO) tolerance over the full course of 30 disinfection cycles; however, the diameters of comfilcon A, senofilcon A, senofilcon C, and samfilcon A lenses soaked in Puremoist exceeded ISO tolerance after between 4 and 9 immersion cycles. In contrast, the diameter of lotrafilcon B held tolerance. Similarly, all lenses cycled in Express or Biotrue held tolerance for sagittal depth, while in Puremoist only lotrafilcon B held tolerance. All lenses became less round in all MPSs but held tolerance for both power and central thickness. Given the lack of reported clinical issues with Puremoist when used with lenses other than lotrafilcon B, we propose that it may be appropriate to revisit the ISO test methods and tolerances to determine if they are still applicable for silicone hydrogel lenses.

    更新日期:2019-12-27
  • Production of osteogenic and angiogenic factors by microencapsulated adipose stem cells varies with culture conditions
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-24
    Shirae K. Leslie; David Joshua Cohen; Barbara D. Boyan; Zvi Schwartz

    Growth factors produced by stem cells aid in the bone repair process. We investigated the ability of encapsulated rat adipose‐derived stem cells (rASCs) treated with osteogenic media (OM) to produce growth factors, and determined the optimal combination of OM components that will lead to the production of both osteogenic and angiogenic factors. Our results demonstrate that microencapsulated stem cells were able to produce vascular endothelial growth factor (VEGF), fibroblast growth factor‐2, and bone morphogenetic protein‐2 (BMP2) necessary for bone regeneration. OM led to the reduction of angiogenic factors; however, the removal of dexamethasone restored angiogenic factor production. Additionally, we determined whether the effect of dexamethasone on VEGF and BMP2 varied among rat, rabbit, mouse, and humans. Dexamethasone led to a reduction in VEGF levels in ASCs derived from rats, mice, and humans, while this reduction was absent in rabbit ASCs (rbASCs). Human ASCs (hASCs) from donors of different race and sex showed a similar response to dexamethasone with secreted VEGF levels. BMP2 levels secreted by rbASCs, mouse ASCs (mASCs), and hASCs were independent of the media treatments, while rASCs responded differently in the surrounding media and within the microbeads. In conclusion, microencapsulated ASCs can be treated to produce osteogenic and angiogenic factors for tissue regeneration applications, but outcomes may vary with culture conditions.

    更新日期:2019-12-25
  • Dual growth factor delivery using PLGA nanoparticles in silk fibroin/PEGDMA hydrogels for articular cartilage tissue engineering
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-24
    Milad Fathi‐Achachelouei; Dilek Keskin; Erhan Bat; Nihal E. Vrana; Aysen Tezcaner
    更新日期:2019-12-25
  • Fracture toughness and crack resistance curves of acrylic bone cements
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-20
    Tobias Ziegler; Raimund Jaeger

    The fracture toughness KIc of 11 clinically used acrylic bone cements was studied in air at room temperature with single edge V‐notched beam specimens. By driving the crack step‐wise through the specimens, crack resistance curves (“R‐curves”) were recorded. One group of bone cements showed an increase of the fracture toughness with increasing crack length (including CMW1+G and several Palacos bone cements) whereas another group (including Simplex, SmartSet, Copal and some Palacos bone cements) did not exhibit an R‐curve behavior. The plateau values for KIc ranged from 0.93 MPa√m (Simplex P) to 1.98 MPa√m (Palacos R+G). The observation of the crack growth with an optical microscope revealed some mechanisms influencing the crack growth like the formation of microcracks in the extended damage zone of the crack tip, the attraction of the crack by inclusions or the shielding of the crack tip by bridges in the wake of the crack. Furthermore, bone cements could be distinguished by the pattern of the path the crack followed during propagation. The crack pattern of CMW1+G provides a possible explanation of the distinct R‐curve behavior of this cement.

    更新日期:2019-12-20
  • Predicting the mechanical response of the vaginal wall in ball burst tests based on histology
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-17
    João P. S. Ferreira; Rita Rynkevic; Pedro A. L. S. Martins; Marco P. L. Parente; Nele M. Famaey; Jan Deprest; António A. Fernandes

    A histologically motivated (HM) coefficient that establishes a link between tissue's microstructure and material model through histological data is used in the prediction of the mechanical properties of vaginal tissue that is subjected to multiaxial loading conditions. Therefore, the material parameters were based on an HM coefficient obtained from tensile testing and histological data of comparable tissues. Uniaxial tensile test data and histological data were collected from three groups of sheep at different time points in their life cycle, including virgins, pregnant, and parous ewes. From this data, a correlation between material parameters and histological data was obtained. Spherical indentation (ball burst [BB]) tests were then performed in specimens with similar tissue structure. The histological data of these samples were used in conjunction with the correlations already established for the uniaxial samples data, to define the material parameters of the BB samples. Mechanical properties of the BB specimens were predicted through basic histology and using finite element modeling (FEM) simulations, without direct mechanical measurements. The predicted force and displacement values of the FEM simulation displayed a good correlation with the experimental (BB) testing results. No fitting of the BB results was performed. In this way, the use of uniaxial tests coupled with useful histological information offers a promising approach to predicting macroscopic material behavior under multiaxial loading conditions in biomechanics.

    更新日期:2019-12-18
  • Bio‐conjugation of platelet‐rich plasma and alginate through carbodiimide chemistry for injectable hydrogel therapies
    J. Biomed. Mater. Res. Part B Appl. Biomater. (IF 2.674) Pub Date : 2019-12-17
    Emily A. Growney; Houston R. Linder; Koyal Garg; J. Gary Bledsoe; Scott A. Sell

    Alginate is a highly tailorable, biocompatible polymer whose properties can be tuned to mimic the properties of native nucleus pulposus (NP) tissue. Platelet‐rich plasma (PRP) is a highly accessible, inexpensive, and readily available mix of pro‐regenerative factors. By functionalizing alginate with PRP, a mechanically optimized, bioactive alginate NP analogue may stimulate NP cells to proliferate and accumulate matrix over a longer period of time than if the PRP were solely encapsulated within the hydrogel. In this study, PRP was chemically bound to alginate using carbodiimide chemistry and mechanically, physically, and cytologically compared to plain alginate as well as alginate containing free‐floating lyophilized PRP. The alginates were mechanically and physically characterized; PRP‐conjugated alginate had similar mechanical properties to controls and had the benefit of retained PRP proteins within the hydrogel. Human nucleus pulposus cells (hNPCs) were seeded within the modified alginates and cultured for 14 days. Quantification data of glycosaminoglycans suggests that PRP‐incorporated alginate has the potential to increase ECM production within the characterized alginate constructs, and that PRP‐functionalized alginate can retain protein within the hydrogel over time. This is the first study to functionalize the milieu of PRP proteins onto alginate and characterize the mechanical and physical properties of the modified alginates. This study also incorporates hNPCs into the characterized PRP‐modified alginates to observe phenotypic maintenance when encapsulated within the in situ gelling constructs.

    更新日期:2019-12-18
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