显示样式:     当前期刊: Biomaterials    加入关注       排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Hydrogels with an embossed surface: An all-in-one platform for mass production and culture of human adipose-derived stem cell spheroids
    Biomaterials (IF 8.806) Pub Date : 2018-10-22
    Se-jeong Kim, Jaesung Park, Hayeon Byun, Young-Woo Park, Luke G. Major, Dong Yun Lee, Yu Suk Choi, Heungsoo Shin

    Stem cell spheroids have been studied extensively in organoid culture and therapeutic transplantation. Herein, hydrogels with an embossed surface (HES) were developed as an all-in-one platform that can enable the rapid formation and culture of a large quantity of size-controllable stem cell spheroids. The embossed structure on the hydrogel was adjustable according to the grit designation of the sandpaper. Human adipose-derived stem cells (hADSCs) were rapidly assembled into spheroids on the hydrogel, with their size distribution precisely controlled from 95 ± 6 μm to 181 ± 15 μm depending on surface roughness. The hADSC spheroids prepared from the HES demonstrated expression of stemness markers and differentiation capacity. In addition, HES-based spheroids showed significantly greater VEGF secretion than spheroids grown on a commercially available low-attachment culture plate. Exploiting those advantages, the HES-based spheroids were used for 3D bioprinting, and the spheroids within the 3D-printed construct showed improved retention and VEGF secretion compared to the same 3D structure containing single cell suspension. Collectively, HES would offer a useful platform for mass fabrication and culture of stem cell spheroids with controlled sizes for a variety of biomedical applications.

    更新日期:2018-10-22
  • Defining hydrogel properties to instruct lineage- and cell-specific mesenchymal differentiation
    Biomaterials (IF 8.806) Pub Date : 2018-10-22
    Ben P. Hung, Jenna N. Harvestine, Augustine M. Saiz, Tomas Gonzalez-Fernandez, David E. Sahar, Mark L. Weiss, J. Kent Leach

    The maintenance and direction of stem cell lineage after implantation remains challenging for clinical translation. Aggregation and encapsulation into instructive biomaterials after preconditioning can bolster retention of differentiated phenotypes. Since these procedures do not depend on cell type or lineage, we hypothesized we could use a common, tunable platform to engineer formulations that retain and enhance multiple lineages from different cell populations. To test this, we varied alginate stiffness and adhesive ligand content, then encapsulated spheroids of varying cellularity. We used Design-of-Experiments to determine the effect of these parameters and their interactions on phenotype retention. The combination of parameters leading to maximal differentiation varied with lineage and cell type, inducing a 2–4-fold increase over non-optimized levels. Phenotype was also retained for 4 weeks in a murine subcutaneous model. This widely applicable approach can facilitate translation of cell-based therapies by instructing phenotype in situ without prolonged induction or costly growth factors.

    更新日期:2018-10-22
  • Gemcitabine nanoparticles promote antitumor immunity against melanoma
    Biomaterials (IF 8.806) Pub Date : 2018-10-20
    Yuan Zhang, Xin Bush, Bingfang Yan, Justin A. Chen

    Myeloid-derived suppressor cells (MDSCs) promote tumor-mediated immunosuppression and cancer progression. Gemcitabine (Gem) is a MDSC-depleting chemotherapeutic agent; however, its clinical use is hampered by its drug resistance and inefficient in vivo delivery. Here we describe a strategy to formulate a Gem analogue gemcitabine monophosphate (GMP) into a lipid-coated calcium phosphate (LCP) nanoparticle, and investigate its antitumor immunity and therapeutic effects after systemic administrations. In the syngeneic mouse model of B16F10 melanoma, compared with free Gem, the LCP-formulated GMP (LCP-GMP) significantly induced apoptosis and reduced immunosuppression in the tumor microenvironment (TME). LCP-GMP effectively depleted MDSCs and regulatory T cells, and skewed macrophage polarization towards the antitumor M1 phenotype in the TME, leading to enhanced CD8+ T-cell immune response and profound tumor growth inhibition. Thus, engineering the in vivo delivery of MDSC-depleting agents using nanotechnology could substantially modulate immunosuppressive TME and boost T-cell immune response for enhanced antitumor efficacy.

    更新日期:2018-10-22
  • Chylomicron-pretended nano-bio self-assembling vehicle to promote lymphatic transport and GALTs target of oral drugs
    Biomaterials (IF 8.806) Pub Date : 2018-10-18
    Yuling Mao, Shuang Feng, Shuai Li, Qinfu Zhao, Donghua Di, Yanfeng Liu, Siling Wang

    Lymphatic transport of oral drugs allows extraordinary gains in bioavailability and efficacy through avoidance of first-pass hepatic metabolism and preservation of drugs at lymphatic tissues against lymph-mediated diseases. Chylomicrons can transport dietary lipids absorbed from the intestine to the tissues through lymphatic circulation. Herein, we engineered for the first time a chylomicron-pretended mesoporous silica nanocarrier that utilizes the digestion, re-esterification, and lymphatic transport process of dietary triglyceride to promote lymphatic transport of oral drugs. Taking lopinavir (LNV) as a model antiretroviral drug with disadvantages such as poor solubility, high first-pass effect and off-target deposition, this vehicle exhibited several properties belonging to ideal nanocarriers, including high drug load, amorphous dispersion and controlled release in the gastrointestinal tract. Additionally, a nano-bio interaction was demonstrated between nanoparticles and a key protein involved in chylomicron assembly; this biochemical reaction in cellular was utilized for the first time to promote lymphatic transport of nanocarriers for oral delivery. As a result, the chylomicron-pretended nanocarrier afforded 10.6-fold higher oral bioavailability compared with free LNV and effectively delivered LNV to gut-associated lymphoid tissues, where HIV persists and actively evolves. This approach not only promises a potential application to HIV-infected individuals but also opens a new avenue to other lymph-mediated pathologies such as autoimmune diseases and lymphatic tumor metastasis.

    更新日期:2018-10-19
  • In vivo β-catenin attenuation by the integrin α5-targeting nano-delivery strategy suppresses triple negative breast cancer stemness and metastasis
    Biomaterials (IF 8.806) Pub Date : 2018-10-18
    Yunfei Li, Yajuan Xiao, Hsuan-Pei Lin, Derek Reichel, Younsoo Bae, Eun Y. Lee, Yiguo Jiang, Xuefei Huang, Chengfeng Yang, Zhishan Wang

    Cancer stem cells (CSCs) play pivotal roles in cancer metastasis, and strategies targeting cancer stemness may greatly reduce cancer metastasis and improve patients’ survival. The canonical Wnt/β-catenin pathway plays critical roles in CSC generation and maintenance as well as in normal stem cells. Non-specifically suppressing the Wnt/β-catenin pathway for cancer therapy could be deleterious to normal cells. To achieve specific β-catenin attenuation in cancer cells, we report an integrin α5 (ITGA5)-targeting nanoparticle for treating metastatic triple negative breast cancer (TNBC). We found that ITGA5 is highly expressed in strongly migratory and invasive TNBC cells as well as their lung metastatic foci, which rationalizes active-targeted drug delivery to TNBC cells via ITGA5 ligands such as a commercialized ligand-RGD motif (Arg-Gly-Asp). We modified lipid-polymer hybrid (LPH) nanoparticle for TNBC-targeted delivery of diacidic norcantharidin (NCTD), a potent anti-cancer compound but with short half-life. Notably, in vivo imaging analysis showed that RGD-decorated LPH (RGD-LPH) accumulated more significantly and remained much longer than LPH in nude mouse orthotopic mammary TNBC tumor and lung metastatic tumor, which implicated the feasibility of ITGA5-targeting strategy for treating metastatic TNBC. Moreover, systemic administration of NCTD-loaded RGD-LPH (RGD-LPH-NCTD) reduced nude mouse orthotopic mammary TNBC tumor growth and metastasis more effectively than free NCTD and LPH-NCTD via down-regulating β-catenin. These findings suggest that ITGA5-targeting nanoparticles may provide a facil and unique strategy of specially attenuating β-catenin in vivo for treating metastatic TNBC.

    更新日期:2018-10-18
  • Glycan targeted polymeric antibiotic prodrugs for alveolar macrophage infections
    Biomaterials (IF 8.806) Pub Date : 2018-10-16
    Jasmin Chen, Fang-Yi Su, Debobrato Das, Selvi Srinivasan, Hye-Nam Son, Brian Lee, Frank Radella, Dale Whittington, Taylor Monroe-Jones, T. Eoin West, Anthony Convertine, Shawn Skerrett, Patrick Stayton, Daniel Ratner
    更新日期:2018-10-17
  • A black phosphorus/manganese dioxide nanoplatform: Oxygen self-supply monitoring, photodynamic therapy enhancement and feedback
    Biomaterials (IF 8.806) Pub Date : 2018-10-17
    Jintong Liu, Ping Du, Tianrui Liu, Bernardino J. Córdova Wong, Weiping Wang, Huangxian Ju, Jianping Lei
    更新日期:2018-10-17
  • Tumor microenvironment-manipulated radiocatalytic sensitizer based on bismuth heteropolytungstate for radiotherapy enhancement
    Biomaterials (IF 8.806) Pub Date : 2018-10-15
    Ruyi Zhou, Huamei Wang, Yufei Yang, Chenyang Zhang, Xinghua Dong, Jiangfeng Du, Liang Yan, Guangjin Zhang, Zhanjun Gu, Yuliang Zhao
    更新日期:2018-10-16
  • A 3D tumor microenvironment regulates cell proliferation, peritoneal growth and expression patterns
    Biomaterials (IF 8.806) Pub Date : 2018-10-16
    Daniela Loessner, Anja Rockstroh, Ali Shokoohmand, Boris M. Holzapfel, Ferdinand Wagner, Jeremy Baldwin, Melanie Boxberg, Barbara Schmalfeldt, Ernst Lengyel, Judith A. Clements, Dietmar W. Hutmacher
    更新日期:2018-10-16
  • Untangling the response of bone tumor cells and bone forming cells to matrix stiffness and adhesion ligand density by means of hydrogels
    Biomaterials (IF 8.806) Pub Date : 2018-10-15
    Tongmeng Jiang, Jinmin Zhao, Shan Yu, Zhengwei Mao, Changyou Gao, Ye Zhu, Chuanbin Mao, Li Zheng

    How cancer cells and their anchorage-dependent normal counterparts respond to the adhesion ligand density and stiffness of the same extracellular matrix (ECM) is still not very clear. Here we investigated the effects of ECM adhesion ligand density and stiffness on bone tumor cells (osteosarcoma cells) and bone forming cells (osteoblasts) by using poly (ethylene glycol) diacrylate (PEGDA) and methacrylated gelatin (GelMA) hydrogels. By independently changing the PEGDA and GelMA content in the hydrogels, we achieved crosslinked hydrogel matrix with independently tunable stiffness (1.6, 6 and 25 kPa for 5%, 10%, 15% PEDGA, respectively) and adhesion ligand density (low, medium and high for 0.05%, 0.2%, 0.5% GelMA respectively). By using a series of biochemical and cell biological characterizations as well as in vivo studies, we confirmed that osteosarcoma and osteoblastic cells responded differently to the stiffness and adhesion ligand density within 3D ECM. When cultured within the 3D PEGDA/GelMA hydrogel matrix, osteosarcoma cells are highly dependent on the matrix stiffness via regulating the integrin-mediated focal adhesion (FA) pathway, whereas osteoblasts are highly sensitive to the matrix adhesion ligand density through regulating the integrin-mediated adherens junction (AJ) pathway. However, when seeded on the 2D surface of the hydrogels, osteosarcoma cells behaved differently and became sensitive to the matrix adhesion ligand density because they were “forced” to attach to the substrate, similar to anchorage-dependent osteoblasts. This study might provide new insights into rational design of scaffolds for generating in vitro tumor models to test anticancer therapeutics and for regenerating tissue to repair defects.

    更新日期:2018-10-15
  • A novel scavenging tool for cancer biomarker discovery based on the blood-circulating nanoparticle protein corona
    Biomaterials (IF 8.806) Pub Date : 2018-10-13
    Marilena Hadjidemetriou, Zahraa Al-ahmady, Maurizio Buggio, Joe Swift, Kostas Kostarelos
    更新日期:2018-10-14
  • Seeing the fate and mechanism of stem cells in treatment of ionizing radiation-induced injury using highly near-infrared emissive AIE dots
    Biomaterials (IF 8.806) Pub Date : 2018-10-11
    Cuihong Yang, Xiang Ni, Duo Mao, Chunhua Ren, Jinjian Liu, Yang Gao, Dan Ding, Jianfeng Liu

    Ionizing radiation-induced skin injury is a common and severe side effect of radiotherapy suffered by cancer patients. Although the therapy using stem cells has been demonstrated to be effective, fully grasping their role in the repair of radiation-induced skin damage remains challenging owing to the lack of highly reliable cell trackers. Herein, we report the design and synthesis of a highly near-infrared emissive organic nanodots with aggregation-induced emission (AIE) characteristic, which give excellent performance in seeing the fate and regenerative mechanism of adipose-derived stem cells (ADSCs) in treatment of radiation-induced skin injury. The resultant AIE dots show a rather high quantum yield of 33% in aqueous media, prominent retention ability in ADSCs without leakage, good biocompatibility during the ADSC differentiation and proliferation as well as excellent injury relief capability on radiation-induced endothelial cells injury. In vivo studies reveal that the AIE dots are capable of serving as an effective fluorescent cell tracker to precisely trace the behavior of the transplanted ADSCs in radiation-induced skin injury-bearing mice and help to understand the ADSCs therapeutic mechanism for at least one month. This study will provide new materials and insights into the stem cell therapy of radiation-induced injury.

    更新日期:2018-10-12
  • Sequential modes of crosslinking tune viscoelasticity of cell-instructive hydrogels
    Biomaterials (IF 8.806) Pub Date : 2018-10-12
    Kyle H. Vining, Alexander Stafford, David J. Mooney

    Materials that can mimic the fibrillar architecture of native extracellular matrix (ECM) while allowing for independent regulation of viscoelastic properties may serve as ideal, artificial ECM (aECM) to regulate cell functions. Here we describe an interpenetrating network of click-functionalized alginate, crosslinked with a combination of ionic and covalent crosslinking, and fibrillar collagen type I. Varying the mode and magnitude of crosslinking enables tunable stiffness and viscoelasticity, while altering neither the hydrogel's microscale architecture nor diffusional transport of molecules with molecular weight relevant to typical nutrients. Further, appropriately timing sequential ionic and covalent crosslinking permits self-assembly of collagen into fibrillar structures within the network. Culture of human mesenchymal stem cells (MSCs) in this mechanically-tunable ECM system revealed that MSC expression of immunomodulatory markers is differentially impacted by the viscoelasticity and stiffness of the matrix. Together, these results describe and validate a novel material system for investigating how viscoelastic mechanical properties of ECM regulate cellular behavior.

    更新日期:2018-10-12
  • Biorecognition: A Key to Drug-Free Macromolecular Therapeutics
    Biomaterials (IF 8.806) Pub Date : 2018-10-12
    Jiyuan Yang, Lian Li, Jindřich Kopeček
    更新日期:2018-10-12
  • ROS-sensitive thioketal-linked polyphosphoester-doxorubicin conjugate for precise phototriggered locoregional chemotherapy
    Biomaterials (IF 8.806) Pub Date : 2018-10-11
    Pei Pei, Chunyang Sun, Wei Tao, Jie Li, Xianzhu Yang, Jun Wang
    更新日期:2018-10-11
  • Tumor-microenvironment controlled nanomicelles with AIE property for boosting cancer therapy and apoptosis monitoring
    Biomaterials (IF 8.806) Pub Date : 2018-10-09
    Yixia Qian, Yuehua Wang, Fei Jia, Zihua Wang, Chunyan Yue, Weikai Zhang, Zhiyuan Hu, Weizhi Wang

    Mild acidity matrix, rich blood vessels and special biomarkers constitute the primary tumor microenvironment. Nanoparticles could change their physicochemical characteristics by functionalizing a series of moieties which is responsive towards pH or specific markers. So precise regulation of nanocarrier-based drug delivery systems by the tumor microenvironment has showed great potential for theranostics. Herein, we developed a smart nano delivery system STD-NM, showing tumor microenvironment responsive targeting, efficient drug delivery and precise evaluation of therapeutic effect in vivo. STD-NM kept in ‘stealth’ state in normal environment while ‘activated’ in the tumor acidic environment, which could show stability in blood circulation while deeply penetrate into tumor tissues. Additionally, STD-NM was designed with aggregation-induced emission (AIE) characteristic, of which the fluorescence ‘switch on’ when apoptosis taken place. Gene analysis by RNA-seq also confirmed a superior therapeutic effect of drug loaded STD-NM treatment. We envisioned the well-designed smart nano materials for drug delivery could open a new avenue in precisely tumor imaging and specific cancer therapeutics.

    更新日期:2018-10-10
  • Thermochromism-induced temperature self-regulation and alternating photothermal nanohelix clusters for synergistic tumor chemo/photothermal therapy
    Biomaterials (IF 8.806) Pub Date : 2018-10-08
    Peng Tang, Yongchun Liu, Yiming Liu, Hongru Meng, Zeying Liu, Ke Li, Daocheng Wu
    更新日期:2018-10-08
  • Optically robust, highly permeable and elastic protein films that support dual cornea cell types
    Biomaterials (IF 8.806) Pub Date : 2018-10-08
    Behnaz Aghaei-Ghareh-Bolagh, Juan Guan, Yiwei Wang, Adam D. Martin, Rebecca Dawson, Suzanne M. Mithieux, Anthony S. Weiss

    Damaged corneas can lead to blindness. Due to the worldwide shortage of donor corneas there is a tremendous unmet demand for a robust corneal replacement that supports growth of the major corneal cell types. Commercial artificial corneas comprise plastic polymers that do not adequately support diverse cell growth. We present a new class of protein elastomer-dominated synthetic corneas with attractive performance that intimately couple biologically active tropoelastin to mechanically robust and durable protein silk. Fabricated films substantially replicate the natural cornea physically and by interacting with both key cells types used in cornea repair. Performance encompasses optical clarity at high transmittance, compatible refractive index, substantial glucose permeability, compliant mechanical properties, and support of both growth and function of corneal epithelial and endothelial cells.

    更新日期:2018-10-08
  • Mitochondria and plasma membrane dual-targeted chimeric peptide for single-agent synergistic photodynamic therapy
    Biomaterials (IF 8.806) Pub Date : 2018-10-05
    Hong Cheng, Rong-Rong Zheng, Gui-Ling Fan, Jing-Hao Fan, Lin-Ping Zhao, Xue-Yan Jiang, Bin Yang, Xi-Yong Yu, Shi-Ying Li, Xian-Zheng Zhang

    Mitochondria and cell membrane play important roles in maintaining cellular activity and stability. Here, a single-agent self-delivery chimeric peptide based nanoparticle (designated as M-ChiP) was developed for mitochondria and plasma membrane dual-targeted photodynamic tumor therapy. Without additional carrier, M-ChiP possessed high drug loading efficacy as well as the excellent ability of producing reactive oxygen species (ROS). Moreover, the dual-targeting property facilitated the effective subcellular localization of photosensitizer protoporphyrin IX (PpIX) to generate ROS in situ for enhanced photodynamic therapy (PDT). Notably, plasma membrane-targeted PDT would enhance the membrane permeability to improve the cellular delivery of M-ChiP, and even directly disrupt the cell membrane to induce cell necrosis. Additionally, mitochondria-targeted PDT would decrease mitochondrial membrane potential and significantly promote the cell apoptosis. Both in vitro and in vivo investigations indicated that this combinatorial PDT in mitochondria and plasma membrane could achieve the therapeutic effect maximization with reduced side effects. The single-agent self-delivery system with dual-targeting strategy was demonstrated to be a promising nanoplatform for synergistic tumor therapy.

    更新日期:2018-10-06
  • Guided Tissue Engineering for Healing of Cancellous and Cortical Bone Using a Combination of Biomaterial Based Scaffolding and Local Bone Active Molecule Delivery
    Biomaterials (IF 8.806) Pub Date : 2018-10-04
    Deepak Bushan Raina, Irfan Qayoom, David Larsson, Ming Hao Zheng, Ashok Kumar, Hanna Isaksson, Lars Lidgren, Magnus Tägil

    A metaphyseal bone defect due to infection, tumor or fracture leads to loss of cancellous and cortical bone. An animal model separating the cancellous and cortical healing was used with a combination of a macroporous gelatin-calcium sulphate-hydroxyapatite (Gel-CaS-HA) biomaterial as a cancellous defect filler, and a thin collagen membrane (CM) guiding cortical bone regeneration. The membrane was immobilized with bone morphogenic protein-2 (rhBMP-2) to enhance the osteoinductive properties. The Gel-CaS-HA cancellous defect filler contained both rhBMP-2 and a bisphosphonate, (zoledronate=ZA) to prevent premature callus resorption induced by the pro-osteoclast effect of rhBMP-2 alone. In the first part of the study, the CM delivering both rhBMP-2 and ZA was tested in a muscle pouch model in rats and the co-delivery of rhBMP-2 and ZA via the CM resulted in higher amounts of bone compared to rhBMP-2 alone. Secondly, an established tibia defect model in rats was used to study cortical and cancellous bone regeneration. The defect was left empty, filled with Gel-CaS-HA alone, Gel-CaS-HA immobilized with ZA or Gel-CaS-HA immobilized with rhBMP-2+ZA. Functionalization of the Gel-CaS-HA scaffold with bioactive molecules produced significantly more bone in the cancellous defect and its surroundings but cortical defect healing was delayed likely due to the protrusion of the Gel-CaS-HA into the cortical bone. To guide cortical regeneration, the cortical defect was sealed endosteally by a CM with or without rhBMP-2. Subsequently, the cancellous defect was filled with Gel-CaS-HA containing ZA and rhBMP-2+ZA. In the groups where the CM was doped with rhBMP-2, significantly higher number of cortices bridged. The approach to guide cancellous as well as cortical bone regeneration separately in a metaphyseal defect using two bioactive molecule immobilized biomaterials is promising and could improve the clinical care of patients with metaphyseal defects.

    更新日期:2018-10-05
  • Beyond RGD; nanoclusters of syndecan- and integrin-binding ligands synergistically enhance cell/material interactions
    Biomaterials (IF 8.806) Pub Date : 2018-10-04
    Fatemeh Karimi, Varsha Jagannath Thombare, Craig A. Hutton, Andrea J. O'Connor, Greg G. Qiao, Daniel E. Heath
    更新日期:2018-10-04
  • Tissue-specific extracellular matrix scaffolds for the regeneration of spatially complex musculoskeletal tissues
    Biomaterials (IF 8.806) Pub Date : 2018-10-04
    Gráinne M. Cunniffe, Pedro J. Díaz-Payno, Eamon J. Sheehy, Susan E. Critchley, Henrique V. Almeida, Pierluca Pitacco, Simon F. Carroll, Olwyn R. Mahon, Aisling Dunne, Tanya J. Levingstone, Conor J. Moran, Robert T. Brady, Fergal J. O'Brien, Pieter A.J. Brama, Daniel J. Kelly
    更新日期:2018-10-04
  • In vivo hepatocellular expression of interleukin-22 using penetratin-based hybrid nanoparticles as potential anti-hepatitis therapeutics
    Biomaterials (IF 8.806) Pub Date : 2018-10-03
    Wei Chen, Jingyun Luan, Gang Wei, Xuyao Zhang, Jiajun Fan, Wenjing Zai, Shaofei Wang, Yichen Wang, Yanxu Liang, Yanyang Nan, Chuzhen Yin, Yubin Li, Ming-lin Liu, Dianwen Ju

    Hepatocellular injury is the pathological hallmark of hepatitis and a crucial driver for the progression of liver diseases, while the treatment options are commonly restricted. Interleukin-22 (IL-22) has attracted special attention as a potent survival factor for hepatocytes that both prevents and repairs the injury of hepatocytes through activation of STAT3 signaling pathway. We hypothesized that the ability to generate potent expression of IL-22 locally for the treatment of severe hepatocellular injury in hepatitis was a promising strategy to enhance efficacy and overcome off-target effects. Accordingly, we developed a polypeptide penetratin-based hybrid nanoparticle system (PDPIA) carrying IL-22 gene by a self-assembly process. This nanocomplex modified with penetratin featured direct translocation across the cellular or endosomal membrane but mild zeta-potential to facilitate the high cellular internalization and endosomal escape of the gene cargos as well as scarcely Kupffer cells uptake. More importantly, PDPIA afforded preferential liver accumulation and predominant hepatocytes internalization following systemic administration, which showed pharmacologically suitable organ and sub-organ-selective properties. Subsequent studies confirmed a considerable protective role of PDPIA in a model of severe hepatitis induced by concanavalin A, evidenced by reduced hepatocellular injury and evaded immune response. The locally expressed IL-22 by PDPIA activated STAT3/Erk signal transduction, and thus promoted hepatocyte regeneration, inhibited reactive oxygen species (ROS) accumulation as well as prevented the dysfunction of mitochondrial. In addition, this system did not manifest side effects or systemic toxicity in mice. Collectively, the high versatility of PDPIA rendered its promising applications might be an effective agent to treat various hepatic disorders.

    更新日期:2018-10-03
  • Cardiovascular Disease Models: A Game Changing Paradigm in Drug Discovery and Screening
    Biomaterials (IF 8.806) Pub Date : 2018-10-01
    Houman Savoji, Mohammad Hossein Mohammadi, Naimeh Rafatian, Masood Khaksar Toroghi, Erika Yan Wang, Yimu Zhao, Anastasia Korolj, Samad Ahadian, Milica Radisic

    Cardiovascular disease is the leading causes of death worldwide. Although investment in drug discovery and development has been sky-rocketing, the number of approved drugs has been declining. Cardiovascular toxicity due to the therapeutic drug use claims the highest incidence and severity of adverse drug reactions in late-stage clinical development. Therefore, to address this issue, new, additional, replacement and combinatorial approaches are needed to fill the gap in effective drug discovery and screening. The motivation for developing accurate, predictive, models is twofold: first, to study and discover new treatments for cardiac pathologies which are leading in worldwide morbidity and mortality rates; and second, to screen for adverse drug reactions on the heart, a primary risk in drug development. In addition to in vivo animal models, in vitro and in silico models have been recently proposed to mimic the physiological conditions of heart and vasculature. Here, we describe current in vitro, in vivo, and in silico platforms for modelling healthy and pathological cardiac tissues and their advantages and disadvantages for drug screening and discovery applications. We review the pathophysiology and the underlying pathways of different cardiac diseases, as well as the new tools being developed to facilitate their study. We finally suggest a roadmap for employing these non-animal platforms in assessing drug cardiotoxicity and safety.

    更新日期:2018-10-02
  • 更新日期:2018-10-02
  • A facile approach for development of a vaccine made of bacterial double-layered membrane vesicles (DMVs)
    Biomaterials (IF 8.806) Pub Date : 2018-10-01
    Sihan Wang, Jin Gao, Mo Li, Liguo Wang, Zhenjia Wang

    Bacterial infections cause acute and chronic diseases. Antimicrobial resistance and aging-related immune weakness remain challenging in therapy of infectious diseases. Vaccines are however an alternative to prevent bacterial infections. Here we report a facile method to rapidly generate bacterium-membrane-formed nanovesicles as a vaccine using nitrogen cavitation. The vaccine is comprised of double-layered membrane vesicles (DMVs) characterized by cryo-TEM, biochemistry and proteomics, showing DMVs possess the integrity of bacterial membrane and contain a wide range of membrane proteins required for vaccination. In the mouse sepsis model induced by Pseudomonas aeruginosa, we found that DMVs can improve mouse survival after mice were immunized with DMVs. The increased adaptive immunity and unique biodistribution of DMVs were responsible for enhanced protection of bacterial infection. Our studies demonstrate that this simple and innovative approach using nitrogen cavitation would be a promising technology for vaccine developments.

    更新日期:2018-10-01
  • Mesenchymal stem cell-driven activatable photosensitizers for precision photodynamic oncotherapy
    Biomaterials (IF 8.806) Pub Date : 2018-09-28
    Xingshu Li, C-yoon Kim, Jeong Min Shin, Dayoung Lee, Gyoungmi Kim, Hyung-Min Chung, Ki-Sung Hong, Juyoung Yoon
    更新日期:2018-09-29
  • Nitric oxide as an all-rounder for enhanced photodynamic therapy: Hypoxia relief, glutathione depletion and reactive nitrogen species generation
    Biomaterials (IF 8.806) Pub Date : 2018-09-29
    Yongyan Deng, Fan Jia, Shengyu Chen, Zhida Shen, Qiao Jin, Guosheng Fu, Jian Ji

    A glutathione (GSH)-sensitive supramolecular nitric oxide (NO) nanogenerator is developed as an all-rounder for enhanced photodynamic therapy (PDT). By integrating GSH-sensitive NO prodrug into the system via LEGO-like host-guest interaction, the nanocarrier could not only deplete intracellular GSH, but also relieve hypoxia at tumor sites through NO mediated blood vessel relaxation. Furthermore, reactive nitrogen species (RNS) with enhanced biocidal activity could be produced by the reaction between NO and reactive oxygen species (ROS), generated from α-cyclodextrin (α-CD) conjugated S-nitrosothiol and light-activated chlorin e6 (Ce6) respectively. Due to multiple combined effects between NO and PDT, the NO acts as the loaded gunpowder inside a ‘grenade’, ‘explosively’ amplifying the therapeutic effects that the light responsive ‘fuse’ Ce6 could exert. The present work may well serve as an inspiration for future creative approaches of photodynamic cancer therapy.

    更新日期:2018-09-29
  • Evaluation of the host immune response to decellularized lung scaffolds derived from α-Gal knockout pigs in a non-human primate model
    Biomaterials (IF 8.806) Pub Date : 2018-09-28
    Elizabeth C. Stahl, Ryan W. Bonvillain, Clint D. Skillen, Brandon L. Burger, Hidetaka Hara, Whayoung Lee, Cynthia B. Trygg, Peter J. Didier, Brooke F. Grasperge, Nicholas C. Pashos, Bruce A. Bunnell, John Bianchi, David L. Ayares, Kelly I. Guthrie, Bryan N. Brown, Thomas H. Petersen

    Whole organ tissue engineering is a promising approach to address organ shortages in many applications, including lung transplantation for patients with chronic pulmonary disease. Engineered lungs may be derived from animal sources after removing cellular content, exposing the extracellular matrix to serve as a scaffold for recellularization with human cells. However, the use of xenogeneic tissue sources in human transplantation raises concerns due to the presence of the antigenic Gal epitope. In the present study, lungs from wild type or α-Gal knockout pigs were harvested, decellularized, and implanted subcutaneously in a non-human primate model to evaluate the host immune response. The decellularized porcine implants were compared to a sham surgery control, as well as native porcine and decellularized macaque lung implants. The results demonstrated differential profiles of circulating and infiltrating immune cell subsets and histological outcomes depending on the implanted tissue source. Upon implantation, the decellularized α-Gal knockout lung constructs performed similarly to the decellularized wild type lung constructs. However, upon re-implantation into a chronic exposure model, the decellularized wild type lung constructs resulted in a greater proportion of infiltrating CD45+ cells, including CD3+ and CD8+ cytotoxic T-cells, likely mediated by an increase in production of Gal-specific antibodies. The results suggest that removal of the Gal epitope can potentially reduce adverse inflammatory reactions associated with chronic exposure to engineered organs containing xenogeneic components.

    更新日期:2018-09-28
  • Specific discrimination of gram-positive bacteria and direct visualization of its infection towards mammalian cells by a DPAN-based AIEgen
    Biomaterials (IF 8.806) Pub Date : 2018-09-28
    Rong Hu, Fan Zhou, Taotao Zhou, Jianlei Shen, Zhiming Wang, Zujin Zhao, Anjun Qin, Ben Zhong Tang

    The infections caused by gram-positive bacteria (G+) is a major threat to public health due to their high morbidity and mortality, and the identification of G+ with high sensitivity and selectivity is urgently desirable. In this paper, a probe with aggregation-induced emission (AIE) characteristic is developed and used to discriminate G+ from other bacteria and fungus with excellent selectivity. Thanks for its AIE feature, this probe shows intense fluorescence when interacted with G+, and the signal can last for 24 h after incubating with S. aureus, which is benefit for long term tracing of translocation process with high contrast. Moreover, this probe can be used to visualize the infection processes of G+ towards mammalian cells, which provides valuable information for understanding the therapeutic mechanism.

    更新日期:2018-09-28
  • Efficient magnetic enrichment of antigen-specific T cells by engineering particle properties
    Biomaterials (IF 8.806) Pub Date : 2018-09-28
    John W. Hickey, Ariel Y. Isser, Fernando P. Vicente, Samuel B. Warner, Hai-Quan Mao, Jonathan P. Schneck
    更新日期:2018-09-28
  • Side effects-avoided theranostics achieved by biodegradable magnetic silica-sealed mesoporous polymer-drug with ultralow leakage
    Biomaterials (IF 8.806) Pub Date : 2018-09-25
    Chengyi Li, Yi Wang, Yilin Du, Min Qian, Huilin Jiang, Jianxin Wang, Niren Murthy, Rongqin Huang
    更新日期:2018-09-25
  • Immunomodulatory injectable silk hydrogels maintaining functional islets and promoting anti-inflammatory M2 macrophage polarization
    Biomaterials (IF 8.806) Pub Date : 2018-09-25
    Manishekhar Kumar, Prerak Gupta, Sohenii Bhattacharjee, Samit K. Nandi, Biman B. Mandal
    更新日期:2018-09-25
  • Combinatorial cassettes to systematically evaluate tissue-engineered constructs in recipient mice
    Biomaterials (IF 8.806) Pub Date : 2018-09-24
    Subhadip Bodhak, Luis F. de Castro, Sergei A. Kuznetsov, Maeda Azusa, Danielle Bonfim, Pamela G. Robey, Carl G. Simon

    Ectopic bone formation in mice is the gold standard for evaluation of osteogenic constructs. By regular procedures, usually only 4 constructs can be accommodated per mouse, limiting screening power. Combinatorial cassettes (combi-cassettes) hold up to 19 small, uniform constructs from the time of surgery, through time in vivo, and subsequent evaluation. Two types of bone tissue engineering constructs were tested in the combi-cassettes: i) a cell-scaffold construct containing primary human bone marrow stromal cells with hydroxyapatite/tricalcium phosphate particles (hBMSCs + HA/TCP) and ii) a growth factor-scaffold construct containing bone morphogenetic protein 2 in a gelatin sponge (BMP2+GS). Measurements of bone formation by histology, bone formation by X-ray microcomputed tomography (μCT) and gene expression by quantitative polymerase chain reaction (qPCR) showed that constructs in combi-cassettes were similar to those created by regular procedures. Combi-cassettes afford placement of multiple replicates of multiple formulations into the same animal, which enables, for the first time, rigorous statistical assessment of: 1) the variability for a given formulation within an animal (intra-animal variability), 2) differences between different tissue-engineered formulations within the same animal and 3) the variability for a given formulation in different animals (inter-animal variability). Combi-cassettes enable a more high-throughput, systematic approach to in vivo studies of tissue engineering constructs.

    更新日期:2018-09-25
  • Acid-triggered echogenic nanoparticles for contrast-enhanced ultrasound imaging and therapy of acute liver failure
    Biomaterials (IF 8.806) Pub Date : 2018-09-21
    Yebin Go, Hanui Lee, Lipjeong Jeong, Semi Sun, Eunmi Hong, Eunkyeong Jung, Changgon Ko, Joungyeon Noh, Sanghun Park, Moungyoung Lee, Chulgyu Song, Dongwon Lee
    更新日期:2018-09-21
  • Light-triggered theranostic liposomes for tumor diagnosis and combined photodynamic and hypoxia-activated prodrug therapy
    Biomaterials (IF 8.806) Pub Date : 2018-09-21
    Kai Zhang, Yuedong Zhang, Xiangdan Meng, Huiting Lu, Huan Chang, Haifeng Dong, Xueji Zhang

    Hypoxia tumor microenvironment is a major challenge for photodynamical therapy (PDT), and hypoxia-activated chemotherapy combined PDT could be promising for enhanced anticancer therapy. In this study, we report an innovative 2-nitroimidazole derivative conjugated polyethylene glycol (PEG) amphoteric polymer theranostic liposome encapsulated a photosensitizer Chlorin e6 (Ce6), hypoxia-activated prodrug Tirapazamine (TPZ) and gene probe for synergistic photodynamic-chemotherapy. Ce6-mediated PDT upon irradiation with a laser induces hypoxia, which leads to the disassembly of the liposome and activates the antitumor activity of TPZ for improved cancer cell-killing. The released co-delivered gene probe could effectively detect the oncogenic intracellular biomarker for diagnosis. Both in vitro and in vivo studies demonstrated the greatly improved anti-cancer activity compared to conventional PDT. This work contributes to the design of hypoxia-responsive multifunctional liposome for tumor diagnosis and hypoxia-activated chemotherapy combined PDT for synergetic therapy, which holds great promise for future cancer therapy.

    更新日期:2018-09-21
  • The effects of a functionally-graded scaffold and bone marrow-derived mononuclear cells on steroid-induced femoral head osteonecrosis
    Biomaterials (IF 8.806) Pub Date : 2018-09-20
    Masahiro Maruyama, Akira Nabeshima, Chi-Chun Pan, Anthony W. Behn, Timothy Thio, Tzuhua Lin, Jukka Pajarinen, Toshiyuki Kawai, Michiaki Takagi, Stuart B. Goodman, Yunzhi Peter Yang

    Osteonecrosis of the femoral head (ONFH) is a debilitating disease that may progress to femoral head collapse and subsequently, degenerative arthritis. Although injection of bone marrow-derived mononuclear cells (BMMCs) is often performed with core decompression (CD) in the early stage of ONFH, these treatments are not always effective in prevention of disease progression and femoral head collapse. We previously described a novel 3D printed, customized functionally-graded scaffold (FGS) that improved bone growth in the femoral head after CD in a normal healthy rabbit, by providing structural and mechanical guidance. The present study demonstrates similar results of the FGS in a rabbit steroid-induced osteonecrosis model. Furthermore, the injection of BMMCs into the CD decreased the osteonecrotic area in the femoral head. Thus, the combination of FGS and BMMC provides a new therapy modality that may improve the outcome of CD for early stage of ONFH by providing both enhanced biological and biomechanical cues to promote bone regeneration in the osteonecrotic area.

    更新日期:2018-09-20
  • Internal decompression of the acutely contused spinal cord: Differential effects of irrigation only versus biodegradable scaffold implantation
    Biomaterials (IF 8.806) Pub Date : 2018-09-19
    James D. Guest, Simon W. Moore, Alex A. Aimetti, Artem B. Kutikov, Andrea J. Santamaria, Christoph P. Hofstetter, Alexander E. Ropper, Nicholas Theodore, Thomas R. Ulich, Richard T. Layer
    更新日期:2018-09-20
  • Hierarchical structured and programmed vehicles deliver drugs locally to inflamed sites of intestine
    Biomaterials (IF 8.806) Pub Date : 2018-09-19
    Wei Li, Yunzhan Li, Zehua Liu, Nattha Kerdsakundee, Ming Zhang, Feng Zhang, Xueyan Liu, Tomás Bauleth-Ramos, Wenhua Lian, Ermei Mäkilä, Marianna Kemell, Yaping Ding, Bruno Sarmento, Ruedeekorn Wiwattanapatapee, Jarno Salonen, Hongbo Zhang, Jouni T. Hirvonen, Dongfei Liu, Hélder A. Santos
    更新日期:2018-09-20
  • Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment
    Biomaterials (IF 8.806) Pub Date : 2018-09-18
    Juan J. Arroyo-Crespo, Ana Armiñán, David Charbonnier, Leandro Balzano-Nogueira, Francisco Huertas-López, Cristina Martí, Sonia Tarazona, Jerónimo Forteza, Ana Conesa, María J. Vicent
    更新日期:2018-09-19
  • A rational tissue engineering strategy based on three-dimensional (3D) printing for extensive circumferential tracheal reconstruction
    Biomaterials (IF 8.806) Pub Date : 2018-09-19
    Jeong Hun Park, Ju Young Park, Inn-Chul Nam, Minjun Ahn, Jae Yeon Lee, Seok Hwa Choi, Sung Won Kim, Dong-Woo Cho

    Extensive circumferential tracheal defects remain a major challenging problem in the field of tracheal reconstruction. In this study, a tissue-engineered tracheal graft based on three-dimensional (3D) printing was developed for extensive circumferential tracheal reconstruction. A native trachea-mimetic bellows scaffold, a framework for a tissue-engineered tracheal graft, was indirectly 3D printed and reinforced with ring-shaped bands made from medical grade silicone rubber. A tissue-engineered tracheal graft was then created by stratifying tracheal mucosa decellularized extracellular matrix (tmdECM) hydrogel on the luminal surface of the scaffold and transferring human inferior turbinate mesenchymal stromal cell (hTMSC) sheets onto the tmdECM hydrogel layer. The tissue-engineered tracheal graft with critical length was anastomosed end-to-end to the native trachea and complete re-epithelialization was achieved on the entire luminal surface within 2 months in a rabbit model with no post-operative complications. With this successful result, the present study reports the preliminary potential of the tissue-engineered tracheal graft as a rational tissue engineering strategy for extensive circumferential tracheal reconstruction.

    更新日期:2018-09-19
  • Improved in situ seeding of 3D printed scaffolds using cell-releasing hydrogels
    Biomaterials (IF 8.806) Pub Date : 2018-09-18
    Michael Whitely, Stacy Cereceres, Prachi Dhavalikar, Karim Salhadar, Thomas Wilems, Brandon Smith, Antonios Mikos, Elizabeth Cosgriff-Hernandez
    更新日期:2018-09-18
  • Rapid 3D bioprinting of decellularized extracellular matrix with regionally varied mechanical properties and biomimetic microarchitecture
    Biomaterials (IF 8.806) Pub Date : 2018-09-18
    Xuanyi Ma, Claire Yu, Pengrui Wang, Weizhe Xu, Xueyi Wan, Cheuk Sun Edwin Lai, Justin Liu, Anna Koroleva-Maharajh, Shaochen Chen
    更新日期:2018-09-18
  • Bone Physiology as Inspiration for Tissue Regenerative Therapies
    Biomaterials (IF 8.806) Pub Date : 2018-09-17
    Diana L. Lopes, Cláudia Martins-Cruz, Mariana B. Oliveira, João F. Mano

    The development, maintenance of healthy bone and regeneration of injured tissue in the human body comprise a set of intricate and finely coordinated processes. However, an analysis of current bone regeneration strategies shows that only a small fraction of well-reported bone biology aspects has been used as inspiration and transposed into the development of therapeutic products. Specific topics that include inter-scale bone structural organization, developmental aspects of bone morphogenesis, bone repair mechanisms, role of specific cells and heterotypic cell contact in the bone niche (including vascularization networks and immune system cells), cell-cell direct and soluble-mediated contact, extracellular matrix composition (with particular focus on the non-soluble fraction of proteins), as well as mechanical aspects of native bone will be the main reviewed topics. In this Review we suggest a systematic parallelization of (i) fundamental well-established biology of bone, (ii) updated and recent advances on the understanding of biological phenomena occurring in native and injured tissue, and (iii) critical discussion of how those individual aspects have been translated into tissue regeneration strategies using biomaterials and other tissue engineering approaches. We aim at presenting a perspective on unexplored aspects of bone physiology and how they could be translated into innovative regeneration-driven concepts.

    更新日期:2018-09-18
  • Original Article for Biomaterials Development of Long In Vivo Tissue-Engineered “Biotube” Vascular Grafts
    Biomaterials (IF 8.806) Pub Date : 2018-09-18
    Yasuhide Nakayama, Maya Furukoshi, Takeshi Terazawa, Ryosuke Iwai

    In-body tissue architecture (iBTA), a cell-free, in vivo tissue engineering technology that can produce autologous implantable tissues of the desired shape by subcutaneously embedding specially designed molds, was used to develop long tubular collagenous tissues called Biotubes. Spiral molds for long Biotubes were designed with an outer pipe-shaped spiral shell and an inner spiral mandrel, and embedded into subcutaneous pouches of beagle dogs or goats for 1 or 2 months. Tubular collagenous tissues were formed at the space between the shell and the mandrel of the mold. Depending on the spiral turn number in the mold, Biotubes of 25 cm or 50 cm (internal diameter 4 mm or 5 mm) were prepared with nearly homogeneous mechanical and histological properties over their entire length. Biotubes stored in 70% ethanol were allogenically implanted into beagle dogs or goats to evaluate their in vivo performance. The 25-cm Biotubes functioned as arterial grafts with no need for luminal modification or mechanical support, and demonstrated vascular reconstruction within 3 months after implantation into dogs. The 50-cm Biotubes functioned as arteriovenous shunt grafts in the neck region of goats without thrombus formation and vascular deformation for 1 month. Thus, the world’s longest tissue-engineered vascular grafts with small diameter could be developed using iBTA.

    更新日期:2018-09-18
  • Viscoelastic properties of microgel thin films control fibroblast modes of migration and pro-fibrotic responses
    Biomaterials (IF 8.806) Pub Date : 2018-09-14
    Daniel Chester, Rahul Kathard, Jeremy Nortey, Kimberly Nellenbach, Ashley C. Brown

    Cell behavior is influenced by the biophysical properties of their microenvironments, and the linear elastic properties of substrates strongly influences adhesion, migration, and differentiation responses. Because most biological tissues exhibit non-linear elastic properties, there is a growing interest in understanding how the viscous component of materials and tissues influences cell fate. Here we describe the use of microgel thin films with controllable non-linear elastic properties for investigating the role of material loss tangent on cell adhesion, migration, and myofibroblastic differentiation, which have implications in fibrotic responses. Fibroblast modes of migration are dictated by film loss tangent; high loss tangent induced ROCK-mediated amoeboid migration while low loss tangent induced Rac-mediated mesenchymal cell migration. Low loss tangent films were also associated with higher levels of myofibroblastic differentiation. These findings have implications in fibrosis and indicate that slight changes in tissue viscoelasticity following injury could contribute to early initiation of fibrotic related responses.

    更新日期:2018-09-15
  • 3D Printed Biofunctionalized Scaffolds for Microfracture Repair of Cartilage Defects
    Biomaterials (IF 8.806) Pub Date : 2018-09-14
    Ting Guo, Maeesha Noshin, Hannah B. Baker, Evin Taskoy, Sean J. Meredith, Qinggong Tang, Julia P. Ringel, Max J. Lerman, Yu Chen, Jonathan D. Packer, John P. Fisher

    While articular cartilage defects affect millions of people worldwide from adolescents to adults, the repair articular cartilage defects still remains challenging due to the limited endogenous regeneration of the tissue and poor integration with implantations. In this study, we developed a 3D-printed scaffold functionalized with aggrecan that supports the cellular fraction of bone marrow released from microfracture, a widely used clinical procedure, and demonstrated tremendous improvement of regenerated cartilage tissue quality and joint function in a lapine model. Optical coherence tomography (OCT) revealed doubled thickness of the regenerated cartilage tissue in the group treated with our aggrecan functionalized scaffold compared to standard microfracture treatment. H&E staining showed 366 ± 95 chondrocytes present in the unit area of cartilage layer with the support of bioactive scaffold, while conventional microfracture group showed only 112 ± 26 chondrocytes. The expression of type II collagen appeared almost 10 times higher with our approach compared to normal microfracture, indicating the potential to overcome the fibro-cartilage formation associated with current microfracture approach. The therapeutic effect was also evaluated at joint function level. The mobility was evaluated using a modified Basso, Beattie and Bresnahan (BBB) scale. While the defect control group showed no movement improvement over the course of study, all experimental groups showed a trend of increasing scores over time. The present work developed an effective method to regenerate critical articular defects by combining a 3D-printed therapeutic scaffold with the microfracture surgical procedure. This biofunctionalized acellular scaffold has great potential to be applied as a supplement for traditional microfracture to improve the quality of cartilage regeneration in a cost and labor effective way.

    更新日期:2018-09-15
  • Biodegradable hypocrellin derivative nanovesicle as a near-infrared light-driven theranostic for dually photoactive cancer imaging and therapy
    Biomaterials (IF 8.806) Pub Date : 2018-09-15
    Xiuli Zheng, Jiechao Ge, Jiasheng Wu, Weimin Liu, Liang Guo, Qingyan Jia, Ying Ding, Hongyan Zhang, Pengfei Wang

    Photoactive agents based on natural products have attracted substantial attention in clinical applications because of their distinct biological activity, molecular structure multiformity, and low biotoxicity. Herein, we initially modify hypocrellin B (HB) with 1,2-diamino-2-methyl propane to form near-infrared (NIR) light (>700 nm)-responsive amino-substituted HB derivative (DPAHB). The DPAHB exhibit broad absorption (400–800 nm), NIR emission (maximum emission peak at 710 nm), and high singlet oxygen (1O2) quantum yield (∼0.33) under NIR light (721 nm) irradiation. After self-assembly by using DPAHB with PEG-PLGA, the as-prepared nanovesicles (DPAHB NVs) retain efficient 1O2 generation, more interestingly, show high photothermal conversion efficiency (∼0.24) under NIR light (721 nm) irradiation for synergistic photodynamic therapy (PDT) and photothermal therapy toward hypoxic tumor. The DPAHB NVs can not only be as a fluorescence/photoacoustic imaging agent but also exhibit an even stronger PDT efficiency than that of chlorin e6 (a widely used classic photosensitizer). In vitro and in vivo studies demonstrate that DPAHB NVs possess high photothermal stability, enhanced tumor accumulation, and suitable biodegradation rate, thus, show a highly promising clinical potential as a new photoactive agent for cancer therapy.

    更新日期:2018-09-15
  • Bioimaging predictors of rilpivirine biodistribution and antiretroviral activities
    Biomaterials (IF 8.806) Pub Date : 2018-09-14
    Brendan M. Ottemann, Austin J. Helmink, Wenting Zhang, Insiya Mukadam, Christopher Woldstad, James R. Hilaire, Yutong Liu, JoEllyn M. McMillan, Benson J. Edagwa, R. Lee Mosley, Jered C. Garrison, Bhavesh D. Kevadiya, Howard E. Gendelman
    更新日期:2018-09-14
  • Biologically activatable azobenzene polymers targeted at drug delivery and imaging applications
    Biomaterials (IF 8.806) Pub Date : 2018-09-14
    Taejun Eom, Wonjae Yoo, Sehoon Kim, Anzar Khan

    Molecular design concepts are described for the preparation of azobenzene polymers capable of showing a tunable response to the rat liver microsome-induced side-chain self-immolation process under hypoxic conditions. It is shown that azobenzene nuclei carrying a donor/acceptor substitution pattern are the most active system towards the enzymatically triggered azobenzene cleavage reaction (half-life = t1/2 = 6 min). Their activity is followed by azobenzene nuclei carrying donor/donor (t1/2 = 20 min), electronically non-substituted (t1/2 = 72 min), and acceptor (t1/2 = 78 min) systems. This trend is preserved when a chemical stimulus, sodium dithionite, replaces the biological reducing conditions and demonstrates generality of the findings, and their potential in proteomics procedures. Furthermore, the established design concepts also permit for variation in polymer structure and topology while still maintaining the electronic substitution pattern. The steric constraints or the inherent character (hydrophilic/hydrophobic) of the azobenzene, however, does not alter the fate of the scission reaction. In all cases, the self-immolation process allows the polymer chain to convert from a chemically neutral to a cationic state. This structural transformation can be used as an activation mechanism (in vitro) to gain entry into cells through electrostatic interactions with the oppositely charged cell membrane and to deliver an anticancer drug. Interestingly, polymer structure now plays a role and bottlebrush-like copolymer show higher selectivity and faster cellular uptake. Finally, the best performing polymer allows for structural modulation into a fluorescent imaging probe. In vivo application to mice suffering from colitis confirms accumulation of the imaging probe in the diseased colon and cecum parts of the body where the endogenous microbial flora is known to produce the activation enzyme. This work, therefore, establishes general principles for the molecular design of biologically activatable and cleavable azobenzene-based polymeric scaffolds applicable to delivery and imaging applications.

    更新日期:2018-09-14
  • Immune lipoprotein nanostructures inspired relay drug delivery for amplifying antitumor efficiency
    Biomaterials (IF 8.806) Pub Date : 2018-09-13
    Yue Han, Bixi Ding, Ziqiang Zhao, Huaqing Zhang, Bo Sun, Yuanpei Zhao, Lei Jiang, Jianping Zhou, Yang Ding

    Chemo-immunotherapy represents an appealing approach to improving cancer treatment. Simultaneously administrating chemotherapeutics with immunoadjuvants can elicit potent tumor death and immune responses. Herein, high density lipoprotein (HDL) inspired immune lipoprotein was proposed for relay drug delivery and amplifying antitumor therapy. Lipophilic AS1411 aptamer-immunoadjuvant CpG fused sequences (Apt-CpG-DSPE) were conjugated to facilitate decoration onto HDLs; and doxorubicin (Dox) was successively intercalated into the consecutive base pairs of Apt-CpG to complete immune HDL nanodrug imHDL/Apt-CpG-Dox. For relay drug delivery, imHDL/Apt-CpG-Dox underwent site-specific structure collapse in tumor intercellular substances inspired from HDL biofunctions (sequential module I); subsequently, dissociated Apt-CpG-Dox was endocytosed into tumor cells mediated by the recognition of AS1411 and nucleolin (sequential module II), translocating Dox to nucleus and enabling tumor ablation and antigens release. The liberated CpG motif further evoked antigen recognition, induced vast secretion of pro-inflammatory cytokines and potentiated host antitumor immunity. Our studies demonstrated that HDL biomimetic platform based relay drug delivery strategy outperformed the monotherapy counterparts in malignant tumor models, eventually generating an augmented antitumor efficacy.

    更新日期:2018-09-14
  • Bioinstructive microparticles for self-assembly of mesenchymal stem Cell-3D tumor spheroids
    Biomaterials (IF 8.806) Pub Date : 2018-09-13
    L.P. Ferreira, V.M. Gaspar, J.F. Mano

    3D multicellular tumor spheroids (3D-MCTS) that closely mimic in vitro the complex lung tumor microenvironment (TME) are highly desirable for screening innovative anti-cancer therapeutics. Despite significant improvements in mimicking lung TME, few models have combined tumor-infiltrating mesenchymal stem cells from bone marrow (hBM-MSCs) with heterotypic 3D tumor spheroid models containing ECM mimetic components. Herein, we engineered hybrid 3D-MCTS that combine, for the first time, A549:fibroblasts:hBM-MSCs in heterotypic tri-culture, with bioinstructive hyaluronan microparticles that act as tumor-ECM mimetics and as cell-anchoring hotspots. The obtained results indicated that 3D microspheres provided proper support for cells to self-assemble into compact 3D microtissues and promoted an increase in CD44 expression, emulating the presence of native-ECM hyaluronan. 3D-MCTS size and sphere-like morphology was reproducible and tri-culture models presented the characteristic solid tumors necrotic core. Mesenchymal stem cells tracking in demonstrated that hBM-MSCs migrate to different regions in 3D microtumors mass exhibiting dynamic interactions with cancer cells and stromal fibroblasts, alike in human tumors. Importantly, doxorubicin administration revealed hBM-MSCs effect on cytotoxic responses in 3D tri-culture models and in dual cultures of hBM-MSCs:A549 at 10:1 ratio. Such findings evidence the relevance of including hBM-MSCs in combination with cancer-stromal fibroblasts in 3D in vitro tumor models and the importance to test different cell-to-cell ratios to mimic tumor heterogeneity. In addition, bioinstructive hyaluronan-microparticles were also effective as cell-agglomerating scaffolds and showed potential to be used as an enabling technology for including different ECM components in 3D in vitro models in the future.

    更新日期:2018-09-14
  • Porous PEEK improves the bone-implant interface compared to plasma-sprayed titanium coating on PEEK
    Biomaterials (IF 8.806) Pub Date : 2018-09-13
    F. Brennan Torstrick, Angela S.P. Lin, Daniel Potter, David L. Safranski, Todd A. Sulchek, Ken Gall, Robert E. Guldberg

    Polyether-ether-ketone (PEEK) is one of the most common materials used for load-bearing orthopaedic devices due to its radiolucency and favorable mechanical properties. However, current smooth-surfaced PEEK implants can lead to fibrous encapsulation and poor osseointegration. This study compared the in vitro and in vivo bone response to two smooth PEEK alternatives: porous PEEK and plasma-sprayed titanium coatings on PEEK. MC3T3 cells were grown on smooth PEEK, porous PEEK, and Ti-coated PEEK for 14 days and assayed for calcium content, osteocalcin, VEGF and ALP activity. Osseointegration was investigated by implanting cylindrical implants into the proximal tibiae of male Sprague Dawley rats for 8 weeks. Bone-implant interfaces were evaluated using μCT, histology and pullout testing. Cells on porous PEEK surfaces produced more calcium, osteocalcin, and VEGF than smooth PEEK and Ti-coated PEEK groups. Bone ingrowth into porous PEEK surfaces was comparable to previously reported porous materials and correlated well between μCT and histology analysis. Porous PEEK implants exhibited greater pullout force, stiffness and energy-to-failure compared to smooth PEEK and Ti-coated PEEK, despite Ti-coated PEEK exhibiting a high degree of bone-implant contact. These results are attributed to increased mechanical interlocking of bone with the porous PEEK implant surface. Overall, porous PEEK was associated with improved osteogenic differentiation in vitro and greater implant fixation in vivo compared to smooth PEEK and Ti-coated PEEK. These results suggest that not all PEEK implants inherently generate a fibrous response and that topography has a central role in determining implant osseointegration.

    更新日期:2018-09-13
  • Bridging the gap in peripheral nerve repair with 3D printed and bioprinted conduits
    Biomaterials (IF 8.806) Pub Date : 2018-09-12
    Angela R. Dixon, Shailly H. Jariwala, Zoe Bilis, Joseph R. Loverde, Paul F. Pasquina, Luis M. Alvarez

    Over the past two decades, a number of fabrication methods, including 3D printing and bioprinting, have emerged as promising technologies to bioengineer nerve conduits that closely replicate features of the native peripheral nerve, with the aim of augmenting or supplanting autologous nerve grafts. 3D printing and bioprinting offer the added advantage of rapidly creating composite peripheral nerve matrices from micron-scaled units, using an assortment of synthetic, natural and biologic materials. In this review, we explore the evolution of automated 3D manufacturing technologies for the development of peripheral nerve conduits and discuss aspects of conduit design, based on microarchitecture, material selection, cell and protein inclusion, and mechanical properties, as they are adaptable to 3D printing. Additionally, we highlight advancements in the application of bio-imaging modalities toward the fabrication of patient-specific nerve conduits. Lastly, we outline regulatory as well as clinical challenges that must be surmounted for the translation of 3D printing and bioprinting technology to the clinic. As a whole, this review addresses topics that may situate 3D manufacturing at the forefront of fabrication technologies that are exploited for the generation of future revolutionary therapies like in-situ printing of peripheral nerves.

    更新日期:2018-09-12
  • Spatially controlled assembly of affinity ligand and enzyme cargo enables targeting ferritin nanocarriers to caveolae
    Biomaterials (IF 8.806) Pub Date : 2018-09-12
    Vladimir V. Shuvaev, Makan Khoshnejad, Katherine W. Pulsipher, Raisa Yu Kiseleva, Evguenia Arguiri, Jasmina C. Cheung-Lau, Kathleen M. LeFort, Melpo Christofidou-Solomidou, Radu V. Stan, Ivan J. Dmochowski, Vladimir R. Muzykantov

    One of the goals of nanomedicine is targeted delivery of therapeutic enzymes to the sub-cellular compartments where their action is needed. Endothelial caveolae-derived endosomes represent an important yet challenging destination for targeting, in part due to smaller size of the entry aperture of caveolae (ca. 30–50 nm). Here, we designed modular, multi-molecular, ferritin-based nanocarriers with uniform size (20 nm diameter) for easy drug-loading and targeted delivery of enzymatic cargo to these specific vesicles. These nanocarriers targeted to caveolar Plasmalemmal Vesicle-Associated Protein (Plvap) deliver superoxide dismutase (SOD) into endosomes in endothelial cells, the specific site of influx of superoxide mediating by such pro-inflammatory signaling as some cytokines and lipopolysaccharide (LPS). Cell studies showed efficient internalization of Plvap-targeted SOD-loaded nanocarriers followed by dissociation from caveolin-containing vesicles and intracellular transport to endosomes. The nanocarriers had a profound protective anti-inflammatory effect in an animal model of LPS-induced inflammation, in agreement with the characteristics of their endothelial uptake and intracellular transport, indicating that these novel, targeted nanocarriers provide an advantageous platform for caveolae-dependent delivery of biotherapeutics.

    更新日期:2018-09-12
  • Combination antitumor immunotherapy with VEGF and PIGF siRNA via systemic delivery of multi-functionalized nanoparticles to tumor-associated macrophages and breast cancer cells
    Biomaterials (IF 8.806) Pub Date : 2018-09-11
    Yudong Song, Cui Tang, Chunhua Yin

    Given that vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), over-expressed in breast cancer cells and M2-like tumor-associated macrophages (M2-TAMs) within tumor microenvironment (TME), work synergistically and independently in mediating tumor progression and immunosuppression, combinatorial immune-based approaches targeting them are expected to be a potent therapeutic modality for patients. Here, polyethylene glycol (PEG) and mannose doubly modified trimethyl chitosan (PEG = MT) along with citraconic anhydride grafted poly (allylamine hydrochloride) (PC)-based nanoparticles (NPs) (PEG = MT/PC NPs) with dual pH-responsiveness were developed to deliver VEGF siRNA (siVEGF)/PIGF siRNA (siPIGF) to both M2-TAMs and breast cancer cells for antitumor immunotherapy. With prolonged blood circulation and intelligent pH-sensitivity, PEG = MT/PC NPs were highly accumulated in tumor tissues and then internalized in M2-TAMs and breast cancer cells via mannose-mediated active targeting and passive targeting, respectively. With the charge-reversal of PC, PEG = MT/PC NPs presented effective endosomal/lysosomal escape and intracellular siRNA release, resulting in efficient gene silencing. Due to the synergism between siVEGF and siPIGF in anti-proliferation of tumor cells and reversal of the TME from pro-oncogenic to anti-tumoral, PEG = MT/PC/siVEGF/siPIGF NPs (PEG = MT/PC/siV-P NPs) exerted robust suppression of breast tumor growth and lung metastasis. This combination strategy may provide a promising alternative for breast cancer therapy.

    更新日期:2018-09-11
  • Intramedullary nailing of forearm shaft fractures by biodegradable compared with titanium nails: Results of a prospective randomized trial in children with at least two years of follow-up
    Biomaterials (IF 8.806) Pub Date : 2018-09-11
    Linda Korhonen, Marja Perhomaa, Antti Kyrö, Tytti Pokka, Willy Serlo, Juhani Merikanto, Jaakko Sinikumpu

    There are disadvantages in Elastic Stable Intramedullary Nailing (ESIN) of forearm-shaft fractures, such as the need of implant removal. Biodegradable Intramedullary Nailing (BIN) is a new technique developed for these fractures. We hypothesized that there is no difference in rotational ROM between the patients treated by BIN vs. ESIN.A randomized, controlled clinical trial included patients, aged 5–15 years, requiring surgery for forearm-shaft fractures. Biodegradable polylactide-co-glycolide (PLGA) nails (Activa IM-Nail™, Bioretec Ltd., Finland) were used in 19 and titanium nails (TEN®, SynthesDePuy Ltd., USA) in 16 patients. Rotational ROM of forearm after two years was the primary outcome. Elbow and wrist ROM, pain and radiographic bone healing were secondary outcomes.Forearm rotation was mean 162° and 151° in BIN and ESIN groups, respectively (P = 0.201). No difference between the groups was found in any other ROMs. Three cases in the ESIN vs. none in the BIN group reported pain (P = 0.113). There was no clinically significant residual angulation in radiographs. Two adolescents in the BIN group vs. none in the ESIN (P = 0.245) were excluded because of implant failure; another two with complete bone union suffered from re-injury. Therefore, satisfactory implant stability among older children needs to be studied.

    更新日期:2018-09-11
  • Synthetic α5β1 integrin ligand PHSRN is proangiogenic and neuroprotective in cerebral ischemic stroke
    Biomaterials (IF 8.806) Pub Date : 2018-09-11
    Cheng-Chun Wu, Liang-Chao Wang, Yu-Tin Su, Wei-Yen Wei, Kuen-Jer Tsai

    Ischemic stroke is the leading cause of disability and death worldwide. An effective therapeutic approach is urgently needed. Stroke-induced angiogenesis and neurogenesis are essential mechanisms in the long-term repair. Extracellular matrix proteins are also involved in tissue self-repair. Recently, a PHSRN (Pro-His-Ser-Arg-Asn) peptide from the fibronectin synergistic motif that can promote wound healing in epithelia and induce endothelial proliferation and cancer cell migration was identified. The therapeutic potential of this peptide in stroke is unknown. Here, we examined the potential of PHSRN in stroke therapy using an ischemic rat model of middle cerebral artery occlusion (MCAO). PHSRN reduced the infarct volume in MCAO rats, improved neurological function, and alleviated motor function impairment. PHSRN targeted the damaged brain region and distributed to endothelial cells after intraperitoneal injection. PHSRN significantly promoted angiogenesis and vascular endothelial growth factor secretion through activation of integrin α5β1 and its downstream intracellular signals, e.g., focal adhesion kinase, Ras, cRaf, and extracellular-signal-regulated kinase. PHSRN treatment also stimulated neurogenesis in MCAO rats, and maintained neuronal survival and neuronal morphologic complexity via induction of VEGF secretion. Together, these results provide insights into the role of integrin α5β1 following ischemia and support the feasibility of using PHSRN peptide in stroke therapy.

    更新日期:2018-09-11
  • Stiffness memory of indirectly 3D-printed elastomer nanohybrid regulates chondrogenesis and osteogenesis of human mesenchymal stem cells
    Biomaterials (IF 8.806) Pub Date : 2018-09-10
    Linxiao Wu, Adrián Magaz, Tao Wang, Chaozong Liu, Arnold Darbyshire, Marilena Loizidou, Mark Emberton, Martin Birchall, Wenhui Song
    更新日期:2018-09-11
  • COX-2 Inhibition mediated anti-angiogenic activatable prodrug potentiates cancer therapy in preclinical models
    Biomaterials (IF 8.806) Pub Date : 2018-09-10
    Hyeong Seok Kim, Amit Sharma, Wen Xiu Ren, Jiyou Han, Jong Seung Kim

    Anti-angiogenesis, i.e., blocking the angiogenic pathway, has been considered as an important component in current cancer therapeutic modalities. However, the associated benefits have proven to be modest as tumor angiogenesis and regrowth persist, probably due to other ill-defined complex angiogenic mechanisms. Herein, we developed an indomethacin (IMC) incorporating system to mediate hypoxia responsive prodrug (TA) and diagnostic agent (DA) in cancer theranostic applications. Cyclooxygenase 2 (COX-2) elevated expression in several cancer types is closely associated with severe tumor supporting vascularization factors. Our strategy utilizing COX-2 inhibition augmented the anti-angiogenetic induced hypoxia responsive prodrug activation well. Both in vitro and in vivo results proved that DA and TA exhibited specificity towards COX-2 positive (+ve) HeLa and A549 cancer cell lines and activation under hypoxic conditions. Compared with controls (R1, and anticancer drug SN-38), TA displayed prolonged tumor retention and enhanced therapeutic efficacy in xenograft mouse models at a reduced dosage. Our results significantly highlighted the importance of COX-2 blockade mediated anti-angiogenesis in complementing the hypoxia-responsive drug delivery systems (DDSs) and could to beneficial for the rapid development of more efficacious antitumor therapeutics.

    更新日期:2018-09-11
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
化学 • 材料 期刊列表