Collagen is the key protein of connective tissue (i.e., skin, tendons and ligaments, cartilage, among others) accounting for 25% to 35% of the whole-body protein content, and entitled of conferring mechanical stability. This protein is also a fundamental building block of bone due to its excellent mechanical properties together with carbonated hydroxyapatite minerals. While the mechanical resilience and viscoelasticity have been studied both in vitro and in vivo from the molecule to tissue level, wave propagation properties and energy dissipation have not yet been deeply explored, in spite of being crucial to understand the vibration dynamics of collagenous structures (e.g., eardrum, cochlear membranes) upon impulsive loads. By using a bottom-up atomistic modelling approach, here we study a collagen peptide under two distinct impulsive displacement loads, including longitudinal and transversal inputs. Using a one-dimensional string model as a model system, we investigate the roles of hydration and load direction on wave propagation along the collagen peptide and the related energy dissipation. We find that wave transmission and energy-dissipation strongly depend on the loading direction. Also, the hydrated collagen peptide can dissipate five times more energy than dehydrated one. Our work suggests a distinct role of collagen in term of wave transmission of different tissues such as tendon and eardrum. This study can step towards understanding the mechanical behaviour of collagen upon transient loads, impact loading and fatigue, and designing biomimetic and bio-inspired materials to replace specific native tissues such as the tympanic membrane.

Cardiac tissue engineering holds great potential in regenerating functional cardiac tissues for various applications. The major strategy is to design scaffolds recapitulating the native cardiac microenvironment to enhance cell and tissue functionalities. Among various biomaterial systems, nanofibrous matrices with aligned morphologies and enhanced conductivity incline to induce the formation of oriented engineered cardiac tissues with enhanced functionalities. The challenge is to functionalize the scaffolds with conductive additives without influencing their biocompatibility. In this study, we developed a fully aqueous process for the fabrication of conductive carbon nanotube/silk fibroin (CNT/silk) electrospun scaffolds. The carbon nanotubes are well dispersed within the nanofibers, providing the scaffolds with enhanced conductivity and excellent biocompatibility for the culture of neonatal rat cardiomyocytes with improved cell spreading and enhanced expression of cardiac-specific proteins. Moreover, the aligned CNT/silk fibroin composite scaffolds exhibit abilities to guide the oriented organization of cardiac tissues and the biomimicking distribution of sarcomeres and gap junctions. The findings demonstrate the great potential of the CNT/silk scaffolds prepared through this aqueous processing method in supporting the formation of cardiac tissues with enhanced functionalities.

The vocal fold lamina propria (VFLP), one of the outermost layers of the vocal fold (VF), is composed of tissue-specific extracellular matrix (ECM) proteins and is highly susceptible to injury. Various biomaterials have been clinically tested to treat voice disorders (e.g., hydrogels, fat, hyaluronic acid), but satisfactory recovery of the VF functionality remains elusive. Fibrosis or scar formation in the VF is a major challenge, and the development and refinement of novel therapeutics that promote the healing and normal function of the VF are needed. Injectable hydrogels derived from native tissues have been previously reported with major advantages over synthetic hydrogels, including constructive tissue remodeling and reduced scar tissue formation. This study aims to characterize the composition of a decellularized porcine VFLP-ECM scaffold and the cytocompatibility and potential anti-fibrotic properties of a hydrogel derived from VFLP-ECM hydrogel. In addition, we isolated potential matrix-bound vesicles (MBVs) and macromolecules from the VFLP-ECM that also downregulated smooth muscle actin ACTA2 under TGF-β1 stimulation. The results provide evidence of the unique protein composition of VFLP-ECM and the potential link between the components of VFLP-ECM and the inhibition of transforming growth factor-beta 1 (TGF-β1) signaling observed in vitro when transformed into injectable forms.

The brain machine interface (BMI) describes a group of technologies capable of communicating with excitable nervous tissue within the central nervous system (CNS). BMI’s have seen major advances in recent years but these advances have been impeded due to a deterioration in the signal to noise ratio of recording electrodes over time following insertion into the CNS. This deterioration has been attributed to an intrinsic host tissue response, namely reactive gliosis. Gliosis involves a complex series of immune mediators resulting in encapsulation of implants via the synthesis of pro-inflammatory signaling molecules and the recruitment of glial cells. There is a clinical need to reduce tissue encapsulation in situ and improve long-term neuroelectrode functionality. Physical modification of the electrode surface at the nanoscale could satisfy these requirements by integrating electrochemical and topographical signals to modulate neural cell behaviour. In this study, commercially available platinum iridium (Pt/Ir) microelectrode probes and planar Pt/Ir substrates were nanotopographically (NT) functionalized using femto/picosecond laser processing to generate laser induced periodic surface structures (LIPSS). Three different topographies and their physical properties were assessed by scanning electron microscopy and atomic force microscopy. The electrochemical properties of these interfaces were investigated using electrochemical impedance spectroscopy and cyclic voltammetry. The in vitro response of mixed cortical cultures (embryonic rat E14/E17), was subsequently assessed by confocal microscopy, ELISA and multiplex protein array analysis. Overall LIPSS features improved electrochemical properties of the electrodes, promoted cell alignment and modulated ion channel expression all involved in key neuronal functions. Neuroelectrodes functionalized with nanotopographical LIPSS features were demonstrated on a microwire probe geometry for the first time. Results indicate that LIPSS can promote/enhance chronic electrode functionality whilst promoting an aligned cell network at the electrode interface.

Mesenchymal stem cells (MSCs) based regenerative medicine is widely considered as a promising approach for repairing tissue and re-establishing function in spinal cord injury (SCI). However, low survival rate, uncontrollable migration and differentiation of stem cells after implantation, represent major challenges towards the clinical deployment of this approach. In this study, we fabricated three-dimensional MSCs laden microfibers via electrospinning in a rotating cell culture to mimic nerve tissue, control stem cell behavior and promote integration with the host tissue. The hierarchically aligned fibrin hydrogel was used as the MSCs carrier though a rotating methods, and the aligned fiber structure induced the MSCs aligned adhesion on the surface of the hydrogel to form micro cell fibers. The MSCs laden microfiber implantation enhances the donor MSCs neural differentiation and encourages the migration of host neurons into the injury gap, and significantly promotes nerve fiber regeneration across the injury site. Abundant GAP-43 and NF positive nerve fibers were observed to regenerate in the caudal, rostral and middle sites of the injury position eight weeks after the surgery. The NF fiber density reached to 29±6 per 0.25 mm2 at the middle site, 82±13 per 0.25 mm2 at the adjacent caudal site, and 70±23 at the adjacent rostral site respectively. Similarly, motor axons labeled with 5-HT were significantly regenerated in the injury gap, which was 122±22 at the middle injury site that was beneficial for motor function recovery. Most remarkably, the transplantation of MSCs laden micro fibers significantly improves electrophysiological expression and re-establishes limb motor function. These findings highlight the combination of MSCs with micro hydrogel fibers, and may become a promising method for MSCs implantation and SCI repair.

The common treatment of epithelial ovarian cancer is aggressive surgery followed by platinum-based cytotoxic chemotherapy. However, residual tumor cells are resistant to chemotherapeutic drugs during postoperative recurrence. The treatment of ovarian cancer requires new breakthroughs and advances. In recent years, magnesium alloy has been widely developed as a new biodegradable material because of its great potential in the field of medical devices. From the degradation products of magnesium, biodegradable magnesium implants have great potential in anti-tumor. According to the disease characteristics of ovarian cancer, we choose it to study the anti-tumor characteristics of biodegradable magnesium. We tested the anti-ovarian tumor properties of Mg through both in vivo and in vitro experiments. According to the optical in vivo imaging and relative tumor volume statistics of mice, high-purity Mg wires significantly inhibited the growth of SKOV3 cells in vivo. We find that the degradation products of Mg, Mg2+ and H2, significantly inhibit the growth of SKOV3 cells and promote their apoptosis. Our study suggests a good promise for treatment of ovarian cancer.

We have made two corrections to the published manuscript. (1) The original image of “Control” in Figure 4b was mistakenly inserted. The corrected Figure 4b is shown here. (2) The fluorescent tag of the CD44 antibody in Figures 2e and 4a,b is PerCP/Cy5.5 but was mislabeled as “PE: CD44” at the bottom of these three figure panels. The labels have been corrected to read “PerCP/Cy5.5: CD44”. The “CD44-PE (IM7)” in the eighth line of the “Materials and Methods - Flow Cytometric Analysis and Antibodies” section should be accordingly corrected to read “CD44-PerCP/Cy5.5 (IM7)”. Figure 2. (e) Quantification of CD44+CD62L+ cells (TCM) in sorted CD8+ T cells that were cultured in RPMI1640 medium (Control) and RPMI1640 medium mixed with 0.5% (w/v) or 1% (w/v) alginate for 48 h, respectively. Figure 4. (a) TCM proportions in CD8+ T cells cultured in RPMI1640 medium (Control), RPMI1640 medium mixed with 3.5% (w/v) glucan, or RPMI1640 medium mixed with 1% (w/v) alginate for 48 h. There is no significant difference in viscosity between 3.5% (w/v) glucan and 1% (w/v) alginate-containing mediums. (b, c) TCM proportions in CD8+ T cells cultured for 48 h in RPMI1640 medium (Control), RPMI1640 medium containing mannuronic acid (100 μg/mL), RPMI1640 medium containing guluronic acid (100 μg/mL), or RPMI1640 medium mixed with 1% (w/v) alginate. The corrections do not affect the interpretation or the conclusions of this article. We apologize for these errors and any confusion this might have been caused. This article has not yet been cited by other publications. Figure 2. (e) Quantification of CD44+CD62L+ cells (TCM) in sorted CD8+ T cells that were cultured in RPMI1640 medium (Control) and RPMI1640 medium mixed with 0.5% (w/v) or 1% (w/v) alginate for 48 h, respectively. Figure 4. (a) TCM proportions in CD8+ T cells cultured in RPMI1640 medium (Control), RPMI1640 medium mixed with 3.5% (w/v) glucan, or RPMI1640 medium mixed with 1% (w/v) alginate for 48 h. There is no significant difference in viscosity between 3.5% (w/v) glucan and 1% (w/v) alginate-containing mediums. (b, c) TCM proportions in CD8+ T cells cultured for 48 h in RPMI1640 medium (Control), RPMI1640 medium containing mannuronic acid (100 μg/mL), RPMI1640 medium containing guluronic acid (100 μg/mL), or RPMI1640 medium mixed with 1% (w/v) alginate.

Wear and corrosion damage of biomedical alloys alters the structure and electrochemical properties of the surface heterogeneously. It was hypothesized that local regions on the same surface systematically differ from one another in terms of their impedance characteristics. To test this hypothesis, CoCrMo discs exposed to electrosurgical and inflammatory-species driven damage were characterized using a localized impedance technique, nearfield electrochemical impedance spectroscopy (NEIS), to assess point-specific surface integrity in response to applied damage. It was found that electrosurgical damage, as may arise during primary arthroplasty and revision surgeries, and hydrogen peroxide concentrations of 5-10 mM significantly alters the corrosion susceptibility of the local surface compared to the as-polished CoCrMo surface. A CoCrMo retrieved neck taper (Goldberg score of 4) was scored in different local regions based off of visual appearance, and it was found that there is a direct relationship between increasing debris coverage and decreasing impedance, with the global surface impedance closest to the most severe-scored local region. This non-invasive method, which uses a milli-electrode configuration to test localized regions, can measure the heterogeneous electrochemical impedance of an implant surface, and be tailored to assess specific damage and corrosion mechanisms revealed on retrieval surfaces.

Localized drug delivery to lung cancer can overcome the limitations of systemic nanocarriers including low drug amount reaching lung tissue and severe off-target toxicity. The current work presented novel inhalable nanocomposites as non-invasive platforms for lung cancer therapy. Nanoparticulate liquid crystals (LCNPs) based on monoolein were developed for synergistic co-encapsulation of the cytotoxic chemotherapeutic drug, pemetrexed and the phytoherbal drug, resveratrol (PEM-RES-LCNPs). For active tumor targeting, lactoferrin (LF) and chondroitin sulfate (CS), natural polymers with intrinsic tumor targeting capabilities, were exploited to functionalize the surface of LCNPs using layer-by-layer (LbL) self-assembly approach. To maximize their deep lung deposition, LF/CS-coated PEM-RES-LCNPs were then microencapsulated within various carriers to obtain inhalable nanocomposites via spray-drying technique. The inhalable dry powder nanocomposites prepared using mannitol-inulin-leucine (1:1:1 wt) mixture displayed superior in-vitro aerosolization performance (2.72 µm MMAD and 61.6 % FPF) which ensured deep lung deposition. In lung cancer bearing mice using urethane as a chemical carcinogen, the inhalable LF/CS-coated PEM-RES-LCNPs nanocomposites showed a superior antitumor activity as revealed by considerable decrease of average lung weight, reduced number and diameter of cancerous lung foci, decreased expression of VEGF-1 and increased expression of active caspase-3 as well as reduced Ki-67 expression compared to spray-dried free PEM/RES mixture and positive control. Moreover, in-vivo fluorescence imaging confirmed successful lung deposition of the inhalable nanocomposites. Conclusively, those inhalable liquid crystalline nanocomposites elaborated in the current work could open new avenues for non-invasive lung cancer treatment.

The clinical therapeutics for nerve tissue regeneration and functional recovery after spinal cord injury (SCI) are very limited due to the complex biological processes and inhibitory microenvironment. Advanced biomaterials are highly desired to avoid severe secondary damage and provide guidance for axonal regrowth. Multichannel nanofibrous scaffolds were modified with gelatin and crosslinked by genipin. The gelatin-coated nanofibers exhibited strong binding affinity with neurotrophin-3, which underwent a well-controlled release and highly promoted neuronal differentiation and synapse formation of the seeded neural stem cells. The nanofibrous scaffolds fabricated by combinatorial biomaterials were implanted into complete transected spinal cords in rats. Not only the inflammatory responses and collagen/astrocytic scar formation was limited, but the functional neurons and remyelination was facilitated postsurgery, leading to highly improved functional restoration. This nanofibrous scaffold with high specific surface area can be easily modified with biomolecules, which was proven to be effective for nerve regeneration after transected SCI, and provided a springboard for advanced scaffold design in clinical applications.

Clinical application of amniotic membrane (AM) in vascular reconstruction was limited by poor processability, rapid biodegradation and insufficient hemocompatibility. In this work, decellularized AM was digested to thermosensitive hydrogel and densely crosslinked in nanoscale as “enhanced” collagenous fibers. Via EDC/NHS catalysis, REDV was further grafted to simulate anticoagulant substance on natural-derived blood vessels. This modification approach endowed AM with rapid endothelialization and rare vascular restenosis. Through adjusting fixation condition, the pore size and mechanical stability of fiber network was approximate to those of natural tissue and precisely designed to fit for cells adhesion. AM was synchronously fixed by ADA and EDC/NHS, forming a “double crosslinked” stable structure significantly improved mechanical strength and resistance against enzymic degradation. Hemolytic and platelet adhesion test indicated ADA/REDV-AM could inhibit hemolysis and coagulation. It also exhibited excellent cytocompatibility: They selectively accelerated adsorption and migration of ECs, while impeded adhesion and proliferation of SMCs. It maintained ECs superiority in competitive growth and avoided thrombosis formation in vivo. Furthermore, their property to promote reconstruction and repairment of blood vessels was proved in animal experiment. Overall, the present studies demonstrate ADA/REDV-AM performed a potential application of small diameter artificial vascular intima with rapid endothelialization and reduced SMCs/platelets adhesion.

Supramolecular hydrogels formed by non-covalent bonds are attractive ‘smart’ materials, which can rapidly respond to external stimuli. However, only a handful of supramolecular hydrogels are applicable in tissue engineering, due to the instability and poor-performed mechanical strength of non-covalent crosslinking hydrogels. Thus, a rigid and stable supramolecular hydrogel has been developed based on poly(L-glutamic acid) (PLGA) and 2-ureido-4[1H]pyrimidinones (UPy), and the UPy stacks are non-covalent crosslinking interactions. The hydrogels show excellent mechanical strength and stability, in sharp contrast to non-covalent hydrogels crosslinked by UPy dimers and covalent hydrogels crosslinked by esterification. The hydrogels also exhibit remoldability, self-healing and thermoplastic printing characteristics, which caused by the reversible supramolecular property of UPy stacks. Also, the formation of hydrogels dependent on UPy stacks is further investigated by AFM, SAXS, in-situ XRD, CD and UV-vis spectroscopy. Finally, the hydrogels show commendable biocompatibility and degradability, which have high potential applications in regenerative medicine.

Injectable gels have been used in minimally invasive surgery for tissue regeneration and treatment of inflammatory diseases. However, polymeric hydrogels often fail in cell infiltration due to the presence of dense, cross-linked molecular networks and lack of bioactivity, which causes delayed tissue remodeling. Here we report a thixotropic, cell-infiltrative hydrogel of biofunctionalized nanocellulose that topologically enhances cell infiltration and biochemically upregulates cellular activity for the promotion of tissue remodeling. Biodegradable, sulfonated nanocellulose forms a nanofibrous hydrogel, mimicking cellular microenvironments through crosslinking between nanocellulose and gelatin. Resulting nanocellulose hydrogels showed thixotropy, allowing for single syringe injection. Nanofiber-based hydrogels possess high molecular permeability owing to nano-porous structures. Sulfonate groups on nanocellulose increase protein adsorption and induce cellular extension in vitro. Highly sulfonated nanocellulose hydrogels enhanced cell infiltration and vascularization upon implantation into rats. Macrophage polarization to M2 was observed in nanocellulose hydrogels, which may be involved in tissue remodeling. Injectable, biofunctionalized nanocellulose gels have enormous potential as artificial biomatrices to heal inflammatory diseases through manipulation of the immune system and promotion of tissue remodeling.

The host response to implanted biomaterials can influence the functionality of the materials and modulate the tissue repair and remolding. Macrophages, key cells in the host response to biomaterials, can be polarized into different phenotypes, which are important in regenerative medicine. The objective of this study was to evaluate the effect of chitooligosaccharide (COS) on the modulation of macrophage (RAW 264.7) polarization and the associated osteogenic and angiogenic activities. The results demonstrate that COS can shift the macrophage response to an alternatively activated reparative response, which can then upregulate the expression of anti-inflammatory cytokines. COS can also create an immune-modulated microenvironment, with osteogenesis- and angiogenesis-related proteins and a biological process that further influences the osteogenic/angiogenic differentiation and promotion of bone mesenchymal stem cells (BMSCs) and vascular activation of human umbilical vein endothelial cells (HUVECs). In this work, COS at a low concentration of 4 μg/mL (COS(4)) and suitable polymerization degrees of 5 (Chitopentaose Hydrochloride, COS5), the associated effect on an alternatively activated reparative response and upregulation of anti-inflammatory cytokines expression was better than COS at other concentrations or polymerization degrees. The supernatant from a culture of RAW 264.7 stimulated by COS(4) and COS5 (conditioned medium S-COS(4) and S-COS5), contain more osteogenesis- and angiogenesis-related proteins like DKK-1, OPN, Osteoactivin, and VEGF R1, EGF, IGFBP-5 for positive regulation of osteogenesis/angiogenesis. Specifically, the alkaline phosphatase activity (ALP) and typical osteogenesis-related proteins of BMSCs were significantly influenced by the conditioned media of COS-stimulated macrophages (S-COS(4) and S-COS5). Furthermore, the conditioned media promoted HUVEC proliferation and migration for vascularization. Our results suggest that COS at a low concentration and suitable polymerization degrees has a beneficial effect on immunity modulation (an alternatively activated reparative response), and can modulate osteogenesis/angiogenesis processes for tissue regeneration without using any inductive agent.

Osteolysis and aseptic loosening due to wear at the articulating interfaces of prosthetic joints are considered to be the key concerns for implant failure in load bearing orthopedic applications .In an effort to reduce the wear and processing difficulties of UHMWPE, our research group recently developed HDPE/UHMWPE nanocomposites with chemically modified graphene oxides (mGO). Considering the importance of sterilization, this work explores the influence of -ray dosage of 25 kGy on the clinically relevant performance-limiting properties of these newly developed hybrid nanocomposites, in vitro. Importantly, this work also probes into the cytotoxic effects of the wear debris of different compositions and sizes on osteoblast and human mesenchymal stem cells (hMSCs). In particular, -ray sterilized 1wt% of mGO reinforced HDPE/UHMWPE nanocomposite exhibited an improvement in the oxidative index (16%), free energy of immersion (-12.1 mN/m), surface polarity (5.0 %) and hardness (42%). Consequently, such enhancements resulted in better tribological properties especially coefficient of friction and wear resistance, when compared with UHMWPE. The spectrum of analysis using Transmission electron microscopy (TEM) and in vitro cytocompatibility assessment, demonstrated that phagocytosable (0.5 m to 4.5 m) sterilized 1 mGO wear particles, when present in culture media at 5 mg/ml of concentration, neither induce significant reduction in MC3T3 murine osteoblast and hMSCs cell growth nor cell morphology phenotype, during 24 h, 48 h and 72 h of incubation. Taken together, the present study suggests that-ray sterilized HDPE/UHMWPE/mGO nanocomposites can be utilized as promising articulating surface for the fabrication of implants for total joint replacements.

Bioelastomers have been extensively used in tissue engineering applications due to favorable mechanical stability, tunable properties and chemical versatility. As these materials generally possess low elastic modulus and relatively long gelation time, it is challenging to 3D print them using traditional techniques. Instead, the field of 3D printing has focused preferentially on hydrogels and rigid polyester materials. To develop a versatile approach for 3D printing of elastomers, we used freeform reversible embedding of suspended prepolymers. A family of novel fast photocrosslinakble bioelastomer prepolymers were synthesized from dimethyl itaconate, 1,8-octanediol, and triethyl citrate. Tensile testing confirmed their elastic properties with Young’s moduli in the range of 11-53 kPa. These materials supported cultivation of viable cells and enabled adhesion and proliferation of human umbilical vein endothelial cells (HUVECs). Tubular structures were created by embedding the 3D printed microtubes within a secondary hydrogel that served as a temporary support. Upon photocrosslinking and porogen leaching, the polymers were permeable to small molecules (TRITC-Dextran). The polymer microtubes were assembled on the 96-well plates custom made by hot-embossing, as a tool to connect multiple organs-on-a-chip. The endothelialization of the tubes was performed to confirm that these microtubes can be utilized as vascular tubes to support parenchymal tissues seeded on them.

Photodynamic therapy (PDT) is a non-invasive cancer treatment that requires the co-presence of photosensitizer (PS), oxygen and light. The efficacy of conventional PDT was usually limited by two factors: PS delivery to tumor and hypoxic solid tumor environment. To improve the efficacy of PDT, nanomaterial-based and enzyme-assisted PDT (nano-ezPDT), which integrates enzyme responsive components into nanomedicines, was developed for enhanced PS delivery and oxygen generation. The nano-ezPDT are designed to take full advantage of the catalytic function of locally activated tumor associated enzymes or smuggled exogeneous enzymes. The enhancement of PS release and accumulation is often controlled by endogenous enzymes upregulated at the tumor sites. Oxygen generation, however, relies mostly on catalase-loaded nanomedicines. In this review, we discuss the associated enzymes, constructs and types of nanocarriers, as well as highlight the principle and utility of nano-ezPDT for cancer therapy.

Biomaterial-associated infections often arise from contaminating bacteria adhering to an implant surface that are introduced during surgical implantation and not effectively eradicated by antibiotic treatment. Whether or not infection develops from contaminating bacteria, depends on an interplay between bacteria contaminating the biomaterial surface, and tissue cells trying to integrate the surface with the aid of immune cells. The biomaterial surface plays a crucial role in defining the outcome of this race for the surface. Tissue integration is considered the best protection of a biomaterial implant against infectious bacteria. This paper aims to determine whether and how macrophages aid osteoblasts and human mesenchymal stem cells to adhere and spread over gold-nanoparticle (GNP-)coatings with different hydrophilicity and roughness in absence or presence of contaminating, adhering bacteria. All GNP-coatings had identical chemical surface composition, and water contact angles decreased with increasing roughness. Upon increasing the roughness of the GNP-coatings, the presence of contaminating Staphylococcus epidermidis in bi-culture with cells gradually decreased surface coverage by adhering and spreading cells, as in absence of staphylococci. More virulent Staphylococcus aureus fully impeded cellular adhesion and spreading on smooth gold- or GNP-coatings, while Escherichia coli allowed minor cellular interaction. Murine macrophages in mono-culture tended towards their pro-inflammatory “fighting” M1-phenotype on all coatings to combat the biomaterial, but in bi-cultures with contaminating, adhering bacteria, macrophages demonstrated Ym1 expression, indicative of polarization towards their anti-inflammatory “fix-and-repair” M2-phenotype. Damage repair of cells by macrophages, improved cellular interactions on intermediately hydrophilic/rough (water contact angle 30 degrees/surface roughness 118 nm) GNP-coatings in presence of contaminating, adhering Gram-positive staphylococci, but provided little aid in presence of Gram-negative E. coli. Thus, the merits on GNP-coatings to influence the race for the surface and prevent biomaterial-associated infection critically depend on their hydrophilicity/roughness and the bacterial strain involved in contaminating the biomaterial surface.

Despite the success of vaccines in preventing many infectious diseases, effective vaccines against pathogens with ongoing challenges – such as HIV, malaria, and tuberculosis – remain unavailable. The emergence of new pathogen variants, the continued prevalence of existing pathogens, and the resurgence of yet other infectious agents motivate the need for new, interdisciplinary approaches to direct immune responses. Many current and candidate vaccines, for example, are poorly immunogenic, provide only transient protection, or create risks of regaining pathogenicity in certain immune-compromised conditions. Recent advances in biomaterials research are creating new potential to overcome these challenges through improved formulation, delivery, and control of immune signaling. At the same time, many of these materials systems – such as polymers, lipids, and self-assembly technologies – may achieve this goal while maintaining favorable safety profiles. This review highlights ways in which biomaterials can advance existing vaccines to safer, more efficacious technologies, and support new vaccines for pathogens that do not yet have vaccines. Biomaterials that have not yet been applied to vaccines for infectious disease are also discussed, and their potential in this area is highlighted.

Effective integration of stimulation and direction in bionic scaffolds by materials and microstructure design has been focused in the advancement of nerve regeneration. Hydrogels are the most promising bio-mimicked materials used in developing nerve grafts, but the highly hydrated networks limit the fabrication of hydrogel materials into complex biomedical devices. Herein, a facile lithography-free and spontaneously-micropatterned techniques were used to fabricate a smart protein hydrogel-based scaffold which carried with topographical, electrical, and chemical induction for neural regulation. The synthesized tissue-mimicked silk-gelatin (SG)/polylactic acid (PLA) bilayer system can self-form three-dimensional ordered corrugation micropatterns with well-defined dimensions (wavelength, λ) based on the stress-induced topography. Through magnetically- and topographically- guided deposition of the synthesized NGF-incorporated Fe3O4-graphene nanoparticles (GFPN), a biologically and electrically conductive cell passage with one-dimensional directionality was constructed to allow for controllable constrained geometric effect on neuronal adhesion, differentiation, and neurite orientation. Particularly, the SG with corrugation patterns of λ ~ 30 μm resulted in the optimal cell adhesion and differentiation in response to the pattern guidance. Furthermore, the additional electrical stimulation applied on GFPN-deposited SG resulted in 1.5-fold increase in the neurite elongation by day 7, finally leading to the neuronal connection by day 21. Such hydrogel device with synergistic effects of physical and chemical enhancement on neuronal activity provides an expectable opportunity in the development of next-generation nerve conduits.

It is only very recently that vast application potential of bacterial cellulose-based materials as wound-healing materials, leather-like and electronic material has been realized. Surface functionalization of those materials can help improvement of certain properties like water-repellency, mechanical strength etc. In this paper we reported functionalization of BC surfaces using “click” polymerization for the first time. By this methodology, dense aromatic groups have been incorporated for the improvement in hydrophobicity. For comparative studies, various fluorine-based compounds have been introduced using conventional click reactions. The surface modified-BC materials have been confirmed by various spectroscopic methods. Particularly, the chemical structures of the materials were studied by solid state 13C NMR spectroscopy and ATR-IR spectroscopy. The XPS was used to study the elemental composition of the materials. Moreover, the crystallites changes of modified-BC surfaces were investigated by XRD. Further, the changes in morphology of the material after functionalization were evaluated by SEM and AFM. Finally, water contact angle measurement revealed manyfold increase in hydrophobicity after click polymerization. A video was also provided in ESI to show the application potential of this material for leather-like material.

The study of enzymatic reactions in confined space can provide valuable insight in the natural selection of nanocompartments for biocatalytic processes. Design of nanozyme capsules with the barrel-shaped protein cage of GroEL has been proposed as a promising means to constrain chemical reactions in a spatiotemporally controllable manner. Herein, we further demonstrate with hemin that the open GroEL cavity can provide a favorable microenvironment for shielding hydrophobic catalytically active species. Meanwhile, it is shown that the GroEL-caged hemin nanozyme not only has a significantly higher catalytic activity than merely dispersed hemin, but also exhibits substrate specificity in the model oxidation reactions, which is a merit lacked by natural hemoproteins. To understand the underlying mechanism behind this supramolecular assembly, molecular docking and molecular dynamics simulations were performed to study the detailed interactions of hemin with the protein cage. This revealed the most likely binding mode and preferred binding residues in the paired hydrophobic α-helices lining the GroEL cavity that are genetically encoded for substrate capturing. Finally, we demonstrate that the hemin-GroEL nanozyme has great potential in label-free fluorometric molecular detection when combined with suitable substrates like homovanillic acid. We believe that our strategy is an advantageous tool for studying confined biocatalytic kinetics as simple mimics of protein-based organelles found in nature as well as for designing diverse nanozymes or bio-nanoreactors with the promiscuous GroEL binding cavity.