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Chitosan bio-adhesives bond strongly with various biological tissues, such as skin, mucosa, and internal organs. Their adhesive ability arises from amino acid and hydroxyl groups in chitosan, facilitating interactions with tissue surfaces through chemical (ionic, covalent, and hydrogen) and physical (chain entanglement) bonding. As non-toxic, biodegradable, and biocompatible materials, chitosan bio-adhesives are a safe option for medical therapies. They are particularly suitable for drug delivery, wound healing, and tissue regeneration. In this review, we address chitosan-based bio-adhesives and the mechanisms associated with them. We also discuss different chitosan composite-based bio-adhesives and their biomedical applications in wound healing, drug delivery, hemostasis, and tissue regeneration. Finally, challenges and future perspectives for the clinical use of chitosan-based bio-adhesives are discussed. [ABSTRACT FROM AUTHOR]

Neuronal tissue engineering has immense potential for treating neurological disorders and facilitating nerve regeneration. Conducting polymers (CPs) have emerged as a promising class of materials owing to their unique electrical conductivity and biocompatibility. CPs, such as poly(3,4-ethylenedioxythiophene) (PEDOT), poly(3-hexylthiophene) (P3HT), polypyrrole (PPy), and polyaniline (PANi), have been extensively explored for their ability to provide electrical cues to neural cells. These polymers are widely used in various forms, including porous scaffolds, hydrogels, and nanofibers, and offer an ideal platform for promoting cell adhesion, differentiation, and axonal outgrowth. CP-based scaffolds can also serve as drug delivery systems, enabling localized and controlled release of neurotrophic factors and therapeutic agents to enhance neural regeneration and repair. CP-based scaffolds have demonstrated improved neural regeneration, both in vitro and in vivo, for treating spinal cord and peripheral nerve injuries. In this review, we discuss synthesis and scaffold processing methods for CPs and their applications in neuronal tissue regeneration. We focused on a detailed literature review of the central and peripheral nervous systems. [ABSTRACT FROM AUTHOR]

Nanomaterial composition, morphology, and mechanical performance are critical parameters for tissue engineering. Within this rapidly expanding space, tubular nanomaterials (TNs), including carbon nanotubes (CNTs), titanium oxide nanotubes (TNTs), halloysite nanotubes (HNTs), silica nanotubes (SiNTs), and hydroxyapatite nanotubes (HANTs) have shown significant potential across a broad range of applications due to their high surface area, versatile surface chemistry, well-defined mechanical properties, excellent biocompatibility, and monodispersity. These include drug delivery vectors, imaging contrast agents, and scaffolds for bone tissue engineering. This review is centered on the recent developments in TN-based biomaterials for structural tissue engineering, with a strong focus on bone tissue regeneration. It includes a detailed literature review on TN-based orthopedic coatings for metallic implants and composite scaffolds to enhance in vivo bone regeneration. [ABSTRACT FROM AUTHOR]

Upper limb neurovascular injuries are uncommon in paediatric population [1]in the age group less than 5-year-old. The vascular injuries requiring surgical intervention pose technical difficulties in view of vasospasm and small calibre of the vessels in the paediatric population [2]. The purpose of this study is to present the technique of End to Side anastomosis of brachial artery proving beneficial in vascular repair in children with small calibre vessels with vasospasm than the conventional reverse vein end to end anastomosis. [ABSTRACT FROM AUTHOR]

Approximately half of an adult human's body weight is made up of muscles. Thus, restoring the functionality and aesthetics of lost muscle tissue is critical. The body is usually able to repair minor muscle injuries. However, when volumetric muscle loss occurs due to tumour extraction, for instance, the body will form fibrous tissue instead. Gelatin methacryloyl (GelMA) hydrogels have been applied for drug delivery, tissue adhesive, and various tissue engineering applications due to their tuneable mechanical properties. Here, we have synthesised GelMA from different gelatin sources (i.e., porcine, bovine, and fish) with varying bloom numbers, which refers to the gel strength, and investigated for the influence of the source of gelatin and the bloom number on biological activities and mechanical properties. The results indicated that the source of the gelatin and variable bloom numbers have an impact on GelMA hydrogel properties. Furthermore, our findings established that the bovine-derived gelatin methacryloyl (B-GelMA) has better mechanical properties than the other varieties composed of porcine and fish with 60 kPa, 40 kPa, and 10 kPa in bovine, porcine, and fish, respectively. Additionally, it showed a noticeably greater swelling ratio (SR) ~1100% and a reduced rate of degradation, improving the stability of hydrogels and giving cells adequate time to divide and proliferate to compensate for muscle loss. Furthermore, the bloom number of gelatin was also proven to influence the mechanical properties of GelMA. Interestingly, although GelMA made of fish had the lowest mechanical strength and gel stability, it demonstrated excellent biological properties. Overall, the results emphasise the importance of gelatin source and bloom number, allowing GelMA hydrogels to have a wide range of mechanical and excellent biological properties and making them suitable for various muscle tissue regeneration applications. [ABSTRACT FROM AUTHOR]

Current therapeutic treatments for the repair and/or replacement of damaged skin following disease or traumatic injury is severely limited. The chicken eggshell membrane (ESM) is a unique material: its innate physical and mechanical characteristics offer optimal barrier properties and, as a naturally derived extract, it demonstrates inherent biocompatibility/biodegradability. To further enhance its therapeutic and clinical potential, the ESM can be modified with the thermo-responsive polymer, poly(N-isopropylacrylAmide) (PNIPAAm) as well as the incorporation of (drug-loaded) silver nanoparticles (AgNP); essentially, by a simple change in temperature, the release and delivery of the NP can be targeted and controlled. In this study, ESM samples were isolated using a decellularization protocol, and the physical and mechanical characteristics were profiled using SEM, FT-IR, DSC and DMA. PNIPAAm was successfully grafted to the ESM via amidation reactions and confirmed using FT-IR, which demonstrated the distinctive peaks associated with Amide A (3275 cm−1), Amide B (2970 cm−1), Amide I (1630 cm−1), Amide II (1535 cm−1), CH2, CH3 groups, and Amide III (1250 cm−1) peaks. Confirmation of the incorporation of AgNP onto the stratified membrane was confirmed visually with SEM, qualitatively using FT-IR and also via changes in absorbance at 380 nm using UV-Vis spectrophotometry during a controlled release study for 72 h. The biocompatibility and cytotoxicity of the novel constructs were assessed using human dermal fibroblast (HDFa) and mouse dermal fibroblast (L929) cells and standard cell culture assays. Metabolic activity assessment (i.e., MTS assay), LDH-release profiles and Live/Dead staining demonstrated good attachment and spreading to the samples, and high cell viability following 3 days of culture. Interestingly, longer-term viability (>5 days), the ESM-PNIPAAm and ESM-PNIPAAm (AgNP) samples showed a greater and sustained cell viability profile. In summary, the modified and enhanced ESM constructs were successfully prepared and characterized in terms of their physical and mechanical profiles. AgNP were successfully loaded into the construct and demonstrated a desirable release profile dependent on temperature modulation. Fibroblasts cultured on the extracted ESM samples and ESM-PNIPAAm demonstrated high biocompatibility in terms of high cell attachment, spreading, viability and proliferation rates. As such, this work summarizes the development of an enhanced ESM-based construct which may be exploited as a clinical/therapeutic wound dressing as well as a possible application as a novel biomaterial scaffold for drug development. [ABSTRACT FROM AUTHOR]

Rationale: Idiopathic pulmonary fibrosis (IPF) is characterized by mitochondrial dysfunction. However, details about the non-mitochondrial enzymes that sustain the proliferative nature of IPF are unclear. Aconitases are a family of enzymes that sustain metabolism inside and outside mitochondria. It is hypothesized that aconitase 1 (ACO1) plays an important role in the pathogenesis of IPF given that ACO1 represents an important metabolic hub in the cytoplasm. Objectives: To determine if ACO1 expression in IPF lungs shows specific patterns that may be important in the pathogenesis of IPF. To determine the similarities and differences in ACO1 expression in IPF, bleomycin-treated, and aging lungs. Methods: ACO1 expression in IPF lungs were characterized and compared to non-IPF controls by western blotting, immunostaining, and enzymatic activity assay. ACO1-expressing cell types were identified by multicolor immunostaining. Using similar methods, the expression profiles of ACO1 in IPF lungs versus bleomycin-treated and aged mice were investigated. Measurements and main results: Lower lobes of IPF lungs, unlike non-IPF controls, exhibit significantly high levels of ACO1. Most of the signals colocalize with von Willebrand factor (vWF), a lineage marker for vascular endothelial cells. Bleomycin-treated lungs also show high ACO1 expressions. However, most of the signals colocalize with E-cadherin and/or prosurfactant protein C, representative epithelial cell markers, in remodeled areas. Conclusions: A characteristic ACO1 expression profile observed in IPF vasculatures may be a promising diagnostic target. It also may give clues as to how de novo angiogenesis contributes to the irreversible nature of IPF. [ABSTRACT FROM AUTHOR]

Biodiversity of oribatid mites were investigated in different disturbed and undisturbed soil of orchards, vegetables, field crops, greenhouse, forest plants, organic farm, bio-diversity park, spices crops, vermicompost bed, ornamental and medicinal plants in Navsari Agricultural University campus during the year 2018 and 2019. Among 3 suborders Brachypylina contributed 66 per cent of total species recorded in Navsari Agricultural University campus. Total 8 species of the suborder Brachypylina were recorded on different agro-ecosystem and fallow land. Out of all 12 species, the proportion of S. curvialatus was highest (20.67%) and was followed by Scheloribates sp. (15.77%), O. kuehnelti (14.95%), S. huancayensis (10.21%) and J. kuehnelti (10.05%). Maximum numbers of oribatid species were recorded during August-November and moderate population was observed in June-July months during the survey period in different agro-ecosystems. The value of Shannon index of diversity for oribatid mites at Navsari Agricultural University campus is 2.2340 and value of Simpson’s index is 0.1253, evenness of oribatid mite species was 0.6650 while, species richness is 12. [ABSTRACT FROM AUTHOR]

Introduction: Chronic cough is a highly problematic symptom for patients with idiopathic pulmonary fibrosis (IPF); limited therapeutic options are available. We evaluated gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough in IPF. Methods: This randomized, double-blind, placebo-controlled, crossover study included subjects with IPF. Sequence A included gefapixant 50 mg BID (period 1; 14 days) followed by placebo (period 2; 14 days); sequence B had the opposite sequence of treatments. This regimen was specified in a protocol amendment that modified the original active treatment regimen of gefapixant 50 mg BID for 10 days and 150 mg BID for 4 days. Patients randomized to the original treatment regimen were excluded from efficacy analyses but included in safety assessments. The primary efficacy endpoint was change from baseline in awake cough frequency (coughs/hour) from periods 1 and 2 combined. Adverse events (AEs) were monitored throughout the study. Results: A total of 51 subjects were randomized, 44 of whom were randomized to treatment sequences evaluated in the primary efficacy analysis (i.e., 22 subjects in sequence A and 22 subjects in sequence B); seven subjects received the treatment assigned before the protocol amendment and were excluded from efficacy analyses. The change from baseline in awake cough frequency from periods 1 and 2 combined (mixed model for repeated measures analysis) did not demonstrate a significant reduction versus placebo in cough at day 14 (p = 0.90); in a post hoc analysis of log-transformed data p value for reduction versus placebo at day 14 was 0.07. The most common AEs were related to taste (dysgeusia and ageusia). Conclusions: Gefapixant was generally well tolerated but was not associated with a significant improvement in chronic cough in subjects with IPF as defined by the primary endpoint in this study. Trial Registration: NCT02502097. [ABSTRACT FROM AUTHOR]

Glial cell alignment in tissue engineered constructs is essential for achieving functional outcomes in neural recovery. While gelatin methacrylate (GelMA) hydrogel offers superior biocompatibility along with permissive structure and tailorable mechanical properties, phosphate glass fibers (PGFs) can provide physical cues for directionality of neural growth. Aligned PGFs were fabricated by a melt quenching and fiber drawing method and utilized with synthesized GelMA hydrogel. The mechanical properties of GelMA and biocompatibility of the GelMA‐PGFs composite were investigated in vitro using rat glial cells. GelMA with 86% methacrylation degree were photo‐crosslinked using 0.1%wt photo‐initiator (PI). Photocrosslinking under UV exposure for 60 s was used to produce hydrogels (GelMA‐60). PGFs were introduced into the GelMA before crosslinking. Storage modulus and loss modulus of GelMA‐60 was 24.73 ± 2.52 and 1.08 ± 0.23 kN/m2, respectively. Increased cell alignment was observed in GelMA‐PGFs compared with GelMA hydrogel alone. These findings suggest GelMA‐PGFs can provide glial cells with physical cues necessary to achieve cell alignment. This approach could further be used to achieve glial cell alignment in bioengineered constructs designed to bridge damaged nerve tissue. [ABSTRACT FROM AUTHOR]

The eggshell membrane (ESM) is an abundant resource with innate complex structure and composition provided by nature. With at least 60 million tonnes of hen eggs produced globally per annum, utilisation of this waste resource is highly attractive in positively impacting sustainability worldwide. Given the morphology and mechanical properties of this membrane, it has great potential as a biomaterials for wound dressing. However, to date, no studies have demonstrated nor reported this application. As such, the objective of this investigation was to identify and optimise a reproducible extraction protocol of the ESM and to assess the physical, chemical, mechanical and biological properties of the substrate with a view to use as a wound dressing. ESM samples were isolated by either manual peeling (ESM-strip) or via extraction using acetic acid [ESM-A0.5] or ethylenediaminetetraacetic acid, EDTA [ESM-E0.9]. Energy dispersive X-ray spectroscopy (EDS) confirmed that there were no traces of calcium residues from the extraction process. Fourier transform infrared (FTIR) spectroscopy revealed that the extraction method (acetic acid and EDTA) did not alter the chemical structures of the ESM and also clarified the composition of the fibrous proteins of the ESM. Scanning electron microscopy (SEM) analyses revealed a three-layer composite structure of the ESM: an inner layer as continuous, dense and non-fibrous (limiting membrane), a middle layer with a network of fibres (inner shell membrane) and the outer layer (outer shell membrane) of larger fibres. Material properties including optical transparency, porosity, fluid absorption/uptake, thermal stability, mechanical profiling of the ESM samples were performed and demonstrated suitable profiles for translational applications. Biological in vitro studies using SV40 immortalised corneal epithelial cells (ihCEC) and corneal mesenchymal stromal cells (C-MSC) demonstrated excellent biocompatibility. Taken together, these results document the development of a novel sustainable biomaterial that may be used for ophthalmic wounds and/or other biomedical therapies. [ABSTRACT FROM AUTHOR]

Developing materials with the capability of changing their innate features can help to unravel direct interactions between cells and ligand‐displaying features. This study demonstrates the grafting of magnetic nanohelices displaying cell‐adhesive Arg‐Gly‐Asp (RGD) ligand partly to a material surface. These enable nanoscale control of rapid winding ("W") and unwinding ("UW") of their nongrafted portion, such as directional changes in nanohelix unwinding (lower, middle, and upper directions) by changing the position of a permanent magnet while keeping the ligand‐conjugated nanohelix surface area constant. The unwinding ("UW") setting cytocompatibility facilitates direct integrin recruitment onto the ligand‐conjugated nanohelix to mediate the development of paxillin adhesion assemblies of macrophages that stimulate M2 polarization using glass and silicon substrates for in vitro and in vivo settings, respectively, at a single cell level. Real time and in vivo imaging are demonstrated that nanohelices exhibit reversible unwinding, winding, and unwinding settings, which modulate time‐resolved adhesion and polarization of macrophages. It is envisaged that this remote, reversible, and cytocompatible control can help to elucidate molecular‐level cell–material interactions that modulate regenerative/anti‐inflammatory immune responses to implants. [ABSTRACT FROM AUTHOR]

Current gold standard to treat soft tissue injuries caused by trauma and pathological condition are autografts and off the shelf fillers, but they have inherent weaknesses like donor site morbidity, immuno-compatibility and graft failure. To overcome these limitations, tissue-engineered polymers are seeded with stem cells to improve the potential to restore tissue function. However, their interaction with native tissue is poorly understood so far. To study these interactions and improve outcomes, we have fabricated scaffolds from natural polymers (collagen, fibrin and elastin) by custom-designed processes and their material properties such as surface morphology, swelling, wettability and chemical cross-linking ability were characterised. By using 3D scaffolds, we comprehensive assessed survival, proliferation and phenotype of adipose-derived stem cells in vitro. In vivo, scaffolds were seeded with adipose-derived stem cells and implanted in a rodent model, with X-ray microtomography, histology and immunohistochemistry as read-outs. Collagen-based materials showed higher cell adhesion and proliferation in vitro as well as higher adipogenic properties in vivo. In contrast, fibrin demonstrated poor cellular and adipogenesis properties but higher angiogenesis. Elastin formed the most porous scaffold, with cells displaying a non-aggregated morphology in vitro while in vivo elastin was the most degraded scaffold. These findings of how polymers present in the natural polymers mimicking ECM and seeded with stem cells affect adipogenesis in vitro and in vivo can open avenues to design 3D grafts for soft tissue repair. [ABSTRACT FROM AUTHOR]

Rationale: Lung transplant is an effective treatment option providing survival benefit in patients with cystic fibrosis (CF). Several studies have suggested survival benefit in adults compared with pediatric patients with CF undergoing lung transplant. However, it remains unclear whether this age-related disparity persists in adult subjects with CF.Objectives: We investigated the impact of age at transplant on post-transplant outcomes in adult patients with CF.Methods: The United Network of Organ Sharing Registry was queried for all adult patients with CF who underwent lung transplantation between 1992 and 2016. Pertinent baseline characteristics, demographics, clinical parameters, and outcomes were recorded. The patients were divided into two groups based on age at transplant (18-29 yr old and 30 yr or older). The primary endpoint was survival time. Assessment of post-transplant survival was performed using Kaplan-Meier tests and log-rank tests with multivariable Cox proportional hazards analysis to adjust for confounding variables.Results: A total of 3,881 patients with CF underwent lung transplantation between 1992 and 2016; mean age was 31.0 (± 9.3) years. The 18-29-year-old at transplant cohort consisted of 2,002 subjects and the 30 years or older cohort had 1,879 subjects. Survival analysis demonstrated significantly higher survival in subjects in the 30 years or older cohort (9.47 yr; 95% confidence interval [CI], 8.7-10.2) compared with the 18-29-year-old cohort (5.21 yr; 95% CI, 4.6-5.8). After adjusting for confounders, survival remained higher in recipients aged 30 years or older (hazard ratio, 0.44; 95% CI, 0.2-0.9). Mortality due to allograft failure was significantly lower in patients with CF aged 30 years or older (28% vs. 36.5%; odds ratio [OR], 0.7; 95% CI, 0.6-0.8), whereas the incidence of malignancy was higher in the 30 years or older cohort (8% vs. 2.9%; OR, 3.0; 95% CI, 1.9-4.6).Conclusions: Age at transplant influences lung transplant outcomes in recipients with CF. Subjects with CF aged 30 years or older at transplant have superior survival compared with adult subjects with CF transplanted between the ages 18 and 29 years. [ABSTRACT FROM AUTHOR]

Micro‐ and especially nanofiber‐type of materials are extremely attractive for a number of applications, ranging from separation and analysis to drug delivery and tissue engineering, and the majority of them are currently produced worldwide via the extremely popular and effective electrospinning technique. The addition of specific tailored molecular recognition capability to these electrospun materials via the established molecular imprinting technology can be extremely beneficial for a number of applications, as indicated by the number of examples in the literature over the past 15 years. However, the integration of these two technologies has proven to be quite challenging, mainly due to the different processing methodologies which characterize the two approaches. In this progress report, the practical difficulties related to the combination of electrospinning and molecular imprinting and to the production of molecularly imprinted electrospun fibers are addressed, discussing the main aspects to take into consideration when designing and optimizing the experimental protocols, as well as highlighting the most prolific research applications that have been explored thus far, to conclude with a commercial/industrial and economic perspective on the envisaged market for these hybrid products. [ABSTRACT FROM AUTHOR]

Tailoring the surface of biomaterial scaffolds has been a key strategy to modulate the cellular interactions that are helpful for tissue healing process. In particular, nanotopological surfaces have been demonstrated to regulate diverse behaviors of stem cells, such as initial adhesion, spreading and lineage specification. Here, we tailor the surface of biopolymer nanofibers with carbon nanotubes (CNTs) to create a unique bi-modal nanoscale topography (500 nm nanofiber with 25 nm nanotubes) and report the performance in modulating diverse in vivo responses including inflammation, angiogenesis, and bone regeneration. When administered to a rat subcutaneous site, the CNT-coated nanofiber exhibited significantly reduced inflammatory signs (down-regulated pro-inflammatory cytokines and macrophages gathering). Moreover, the CNT-coated nanofibers showed substantially promoted angiogenic responses, with enhanced neoblood vessel formation and angiogenic marker expression. Such stimulated tissue healing events by the CNT interfacing were evidenced in a calvarium bone defect model. The in vivo bone regeneration of the CNT- coated nanofibers was significantly accelerated, with higher bone mineral density and up-regulated osteogenic signs (OPN, OCN, BMP2) of in vivo bone forming cells. The in vitro studies using MSCs could demonstrate accelerated adhesion and osteogenic differentiation and mineralization, supporting the osteo-promoting mechanism behind the in vivo bone forming event. These findings highlight that the CNTs interfacing of biopolymer nanofibers is highly effective in reducing inflammation, promoting angiogenesis, and driving adhesion and osteogenesis of MSCs, which eventually orchestrate to accelerate tissue healing and bone regeneration process. Here we demonstrate that the interfacing of biopolymer nanofibers with carbon nanotubes (CNTs) could modulate multiple interactions of cells and tissues that are ultimately helpful for the tissue healing and bone regeneration process. The CNT-coated scaffolds significantly reduced the pro-inflammatory signals while stimulating the angiogenic marker expressions. Furthermore, the CNT-coated scaffolds increased the bone matrix production of bone forming cells in vivo as well as accelerated the adhesion and osteogenic differentiation of MSCs in vitro. These collective findings highlight that the CNTs coated on the biopolymer nanofibers allow the creation of a promising platform for nanoscale engineering of biomaterial surface that can favor tissue healing and bone regeneration process, through a series of orchestrated events in anti-inflammation, pro-angiogenesis, and stem cell stimulation. Image, graphical abstract [ABSTRACT FROM AUTHOR]

For skeletal muscle engineering, scaffolds that can stimulate myogenic differentiation of cells while possessing suitable mechanical properties (e.g. flexibility) are required. In particular, the elastic property of scaffolds is of importance which helps to resist and support the dynamic conditions of muscle tissue environment. Here, we developed highly flexible nanocomposite nanofibrous scaffolds made of polycarbonate diol and isosorbide-based polyurethane and hydrophilic nanographene oxide added at concentrations up to 8%. The nano-graphene oxide incorporation increased the hydrophilicity, elasticity, and stress relaxation capacity of the polyurethane-derived nanofibrous scaffolds. When cultured with C2C12 cells, the polyurethane-nano-graphene oxide nanofibers enhanced the initial adhesion and spreading of cells and further the proliferation. Furthermore, the polyurethane-nano-graphene oxide scaffolds significantly up-regulated the myogenic mRNA levels and myosin heavy chain expression. Of note, the cells on the flexible polyurethane-nano-graphene oxide nanofibrous scaffolds could be mechanically stretched to experience dynamic tensional force. Under the dynamic force condition, the cells expressed significantly higher myogenic differentiation markers at both gene and protein levels and exhibited more aligned myotubular formation. The currently developed polyurethane-nano-graphene oxide nanofibrous scaffolds, due to their nanofibrous morphology and high mechanical flexibility, along with the stimulating capacity for myogenic differentiation, are considered to be a potential matrix for future skeletal muscle engineering. [ABSTRACT FROM AUTHOR]

For skeletal muscle engineering, scaffolds that can stimulate myogenic differentiation of cells while possessing suitable mechanical properties (e.g. flexibility) are required. In particular, the elastic property of scaffolds is of importance which helps to resist and support the dynamic conditions of muscle tissue environment. Here, we developed highly flexible nanocomposite nanofibrous scaffolds made of polycarbonate diol and isosorbide-based polyurethane and hydrophilic nano-graphene oxide added at concentrations up to 8%. The nano-graphene oxide incorporation increased the hydrophilicity, elasticity, and stress relaxation capacity of the polyurethane-derived nanofibrous scaffolds. When cultured with C2C12 cells, the polyurethane–nano-graphene oxide nanofibers enhanced the initial adhesion and spreading of cells and further the proliferation. Furthermore, the polyurethane–nano-graphene oxide scaffolds significantly up-regulated the myogenic mRNA levels and myosin heavy chain expression. Of note, the cells on the flexible polyurethane–nano-graphene oxide nanofibrous scaffolds could be mechanically stretched to experience dynamic tensional force. Under the dynamic force condition, the cells expressed significantly higher myogenic differentiation markers at both gene and protein levels and exhibited more aligned myotubular formation. The currently developed polyurethane–nano-graphene oxide nanofibrous scaffolds, due to their nanofibrous morphology and high mechanical flexibility, along with the stimulating capacity for myogenic differentiation, are considered to be a potential matrix for future skeletal muscle engineering. [ABSTRACT FROM AUTHOR]

Highlights • Various nanocrystal shapes of HA were prepared by hydrothermal process. • The synthesized HA's crystals were used for EPD to produce nanostructured coatings. • The rMSC viability on SHA coatings was higher that MHA and LHA coatings. • MHA coatings showed higher cell adhesion compare to SHA and LHA (MHA > SHA > LHA). • MHA coatings showed higher spreading compare to SHA and LHA at 12 and 24 h. Abstract Bioactive nanostructured coating has been a key strategy to improve the cell adhesion and osseointegration of metallic implants. This study presents the electrophoretic coatings of hydroxyapatite with tunable nanocrystal morphologies. The hydroxyapatite nanocrystals were prepared with three different elongated dimensions by the hydrothermal method (∼80 nm; SHA, ∼300 nm; MHA, and ∼900 nm; LHA), which were used in combination with a fugitive biopolymer chitosan for the electrophoretic deposition on titanium. All the HA coatings were densely and homogeneously deposited and had different and unique nanotopologies and corresponding surface areas. The coating parameter significantly altered the cell behaviors including anchorage, spreading and proliferation; the cell adhesion was better on the small- and middle-sized nanocrystals (SHA, MHA > LHA), which was interestingly opposite in cell spreading (LHA > SHA, MHA), and then the cell proliferation was again up-regulated on SHA and MHA. Although more studies are needed to elucidate the biological phenomenon, the sets of results imply the importance of tailored nanocrystal morphology in the initial (adhesion and growth) cellular events. [ABSTRACT FROM AUTHOR]

Cell encapsulating hydrogels with tunable mechanical and biological properties are of special importance for cell delivery and tissue engineering. Silk fibroin and collagen, two typical important biological proteins, are considered potential as cell culture hydrogels. However, both have been used individually, with limited properties ( e.g., collagen has poor mechanical properties and cell-mediated shrinkage, and silk fibroin from Bombyx mori (mulberry) lacks cell adhesion motifs). Therefore, the combination of them is considered to achieve improved mechanical and biological properties with respect to individual hydrogels. Here, we show that the cell-encapsulating hydrogels of mulberry silk fibroin / collagen are implementable over a wide range of compositions, enabled simply by combining the different gelation mechanisms. Not only the gelation reaction but also the structural characteristics, consequently, the mechanical properties and cellular behaviors are accelerated significantly by the silk fibroin / collagen hybrid hydrogel approach. Of note, the mechanical and biological properties are tunable to represent the combined merits of individual proteins. The shear storage modulus is tailored to range from 0.1 to 20 kPa along the iso-compositional line, which is considered to cover the matrix stiffness of soft-to-hard tissues. In particular, the silk fibroin / collagen hydrogels are highly elastic, exhibiting excellent resistance to permanent deformation under different modes of stress; without being collapsed or water-squeezed out ( vs. not possible in individual proteins) – which results from the mechanical synergism of interpenetrating networks of both proteins. Furthermore, the role of collagen protein component in the hybrid hydrogels provides adhesive sites to cells, stimulating anchorage and spreading significantly with respect to mulberry silk fibroin gel, which lacks cell adhesion motifs. The silk fibroin / collagen hydrogels can encapsulate cells while preserving the viability and growth over a long 3D culture period. Our findings demonstrate that the silk / collagen hydrogels possess physical and biological properties tunable and significantly improved ( vs. the individual protein gels), implying their potential uses for cell delivery and tissue engineering. Statement of Significance Development of cell encapsulating hydrogels with excellent physical and biological properties is important for the cell delivery and cell-based tissue engineering. Here we communicate for the first time the novel protein composite hydrogels comprised of ‘Silk’ and ‘Collagen’ and report their outstanding physical, mechanical and biological properties that are not readily achievable with individual protein hydrogels. The properties include i) gelation accelerated over a wide range of compositions, ii) stiffness levels covering 0.1 kPa to 20 kPa that mimic those of soft-to-hard tissues, iii) excellent elastic behaviors under various stress modes (bending, twisting, stretching, and compression), iv) high resistance to cell-mediated gel contraction, v) rapid anchorage and spreading of cells, and vi) cell encapsulation ability with a long-term survivability. These results come from the synergism of individual proteins of alpha-helix and beta-sheet structured networks. We consider the current elastic cell-encapsulating hydrogels of silk-collagen can be potentially useful for the cell delivery and tissue engineering in a wide spectrum of soft-to-hard tissues. [ABSTRACT FROM AUTHOR]

Nanocarriers are one of the key elements to improve the therapeutic potential of signaling molecules, including genes for the disease treatment and tissue repair. Here, a nanocarrier system is reported that delivers genetic molecule small interference RNA (siRNA) for osteoblastic stimulation. For this, a hollow form of mesoporous silica nanoshell (MSns) is designed to load and release siRNA to silence Plekho-1 gene. In particular, a pressure-induced loading method is effective in enhancing the incorporation of siRNA within a hollow space; a loading level attained ≈30% is almost three times higher than that of a non-hollow form. Furthermore, the release of siRNA from the nanocarriers is highly sustainable; continued over 18 d in a diffusion-controlled manner, in striking contrast to the rapid release (3 d) from a non-hollow form. The nanocarriers exhibit excellent cell viability, and the siRNA-nanocarrier complexes are efficiently internalized to osteoblastic cells (uptake level over 90%). The intracellular delivery suppresses the target gene Plekho-1 expression down to 20%, which in turn up-regulates the expression of osteoblast transcriptional factors (Runx2 and Smad2), demonstrating an effective gene delivery system for bone repair. [ABSTRACT FROM AUTHOR]