In vivosoft tissue regenerative potential of flax seed mucilage self-assembled collagen aerogels.

The present study demonstrates thein vivosoft tissue regenerative potential of flax seed mucilage (FSM) reinforced collagen aerogels in Wistar rats. The physiochemical, mechanical, and thermal properties were significantly improved upon the incorporation of flax mucilage into collagen when compared to the native collagen scaffold. In addition, the functional group of flax mucilage notably contributed to a better anti-oxidative potential than the control collagen. The flax mucilage-reinforced collagen at 4 mg ml-1concentration showed a 2-fold increase in porosity compared to native collagen. The tensile strength of native collagen, 2 mg ml-1, and 4 mg ml-1FSM reinforced collagen was 5.22 MPa, 9.76 MPa, and 11.16 MPa, respectively, which indicated that 2 mg ml-1and 4 mg ml-1FSM showed an 87% and 113% percentage increase respectively in tensile strength compared to the native collagen control. FSM-reinforced biomatrix showed 97% wound closure on day 15 post-wounding, indicating faster healing than controls, where complete healing occurred only on day 21. The mechanical properties of skin treated with FSM-reinforced collagen scaffold post-healing were considerably better than native collagen. The histological and immunohistochemistry analysis also showed complete restoration of wounded tissue like intact normal skin. The findings paved the way for the development of collagen-polysaccharide mucilage wound dressing materials and their further application in skin tissue engineering.

Lanthanum Oxide Nanoparticles Reinforced Collagen ƙ-Carrageenan Hydroxyapatite Biocomposite as Angio-Osteogenic Biomaterial for In Vivo Osseointegration and Bone Repair.

A composite biomatrix fabricated with collagen, ƙ-carrageenan, hydroxyapatite reinforced with lanthanum oxide nanoparticles is explored as proangiogenic and osteogenic bone tissue repair biomaterial. The biomatrix shows increased physical and biological stability as observed from proteolytic degradation and thermal stability studies. The addition of lanthanum oxide nanoparticles facilitates good osseointegration coupled with simultaneous activation of proangiogenic properties to act as a bone mimicking material. The minimal level of reactive oxygen species and superior cytocompatibility help the as-synthesized biomatrix in achieving capillary migration into the bone micro environment. The composite biomatrix upregulates the expression of VEGF, VEGF-R2 genes in endothelial cells and osteopontin, osteocalcin in osteoblasts cells, respectively. The in vivo hard tissue repair experiment conducted in a rat model shows complete healing of the bone defect by eight weeks with the application of collagen-ƙ-carrageenan-hydroxyapatite-lanthanum oxide nanoparticle biomaterial when compared to the biomaterial made out of individual constituents alone. The biomaterial matrix gets biointegrated into the bone tissue and exerts its therapeutic value in bringing a faster osseo repair process. The study shows the feasibility of using rare-earth metal nanoparticles in combination with protein-polysaccharide biopolymers for bone regeneration.

White to brown adipocyte transition mediated by Apigenin via VEGF-PRDM16 signaling.

The dysregulated energy metabolism in white adipose tissues results in derangement of biological signaling resulting in obesity. Lack of vascularization in these white adipose tissues is one of the major reasons for dysregulated energy metabolism. Not much work has been done in this direction to understand the role of angiogenesis in white adipose tissue metabolism. In the present study, we evaluated the effect of angiogenic modulator in the metabolism of white adipocyte (WAC). Bioactive Apigenin was selected and its angiogenic ability was studied. Apigenin was shown to be highly proangiogenic hence the effect of Apigenin on de novo and trans-differentiation of WAT was studied. Apigenin showed enhanced de novo differentiation and trans-differentiation of mouse WAC into brown-like phenotype. To understand the effect of Apigenin on adipose tissue vasculature, coculture studies were conducted. Cross talk between endothelial cell and adipocytes were observed in coculture studies. Gene expression studies of cocultured cells revealed that browning of WAC occurred by triggering the expression of Vascular endothelial growth factor A. The study provides a new insight for inducing metabolic shift in WACs by modulation of angiogenesis in WAC microenvironment by the upregulation of PRDM16 cascade to trigger browning for the treatment of obesity.

Lanthanum oxide nanoparticle-collagen bio matrix induced endothelial cell activation for sustained angiogenic response for biomaterial integration.

Rare earth lanthanum oxide nanoparticle reinforced collagen biomatrix that elicited the endothelial cell activation to promote angiogenesis for biomaterial integration was developed and evaluated in the present study. The structural integrity of collagen was not compromised on crosslinking of lanthanum oxide nanoparticle to collagen biomolecule. As-synthesised collagen biomatrix was shown to have improved mechanical strength, a lesser susceptibility to proteolytic degradation and good swelling properties. Superior cytocompatibility, hemocompatibility and minimal ROS generation was observed with Lanthanum oxide nanoparticle reinforced collagen bio matrix. The Lanthanum oxide nanoparticle reinforced collagen bio matrix elicited endothelial cell activation eliciting pro-angiogensis as observed in tube formation and aortic arch assays. The bio-matrix promoted the infiltration and proliferation of endothelial cells which is an unexplored domain in the area of tissue engineering that is very essential for biomaterial integration into host tissue. The wound healing effect of Lanthanum oxide nanoparticle stabilized collagen showed enhanced cell migration in vitro in cells maintained in Lanthanum oxide nanoparticle reinforced collagen bio matrix. The study paves the way for developing rare earth-based dressing materials which promoted biomatrix integration by enhancing vascularisation for tissue regenerative applications in comparison with traditional biomaterials.

Nanotized praseodymium oxide collagen 3-D pro-vasculogenic biomatrix for soft tissue engineering.

The current study explores development of highly vascularizable biomatrix scaffold containing rare-earth metal praseodymium oxide nanoadditives for angiogenic and soft tissue regenerative applications. The therapeutic potential of praseodymium oxide nanoparticles rendered excellent endothelial cell differentiation for inducing pro angiogenic microenvironment by eliciting VE-Cadherin expression in the biomatrix scaffold. The nanoparticles were incorporated into bio-macromolecule collagen which aided in stabilization of collagen by maintaining the structural integrity of collagen and showed less susceptibility towards protease enzymes, high cyto-compatibility and high hemo-compatibility. The scaffold provided 3-dimensional micro-environments for the proliferation of endothelial cells and fibroblast cells promoting the wound healing process in an orchestrated fashion. Biological signal modulatory property of rare earth metal is the unexplored domains that can essentially bring significant therapeutic advancement in engineering advanced biological materials. This study opens potential use of nano-scaled rare earth metals in biomaterial application for tissue regeneration by modulating the pro-angiogenesis and anti-proteolysis properties.

Effect of magnesium ascorbyl phosphate on collagen stabilization for wound healing application.

Wound healing is a complex process which requires appropriate structural support for restoration of tissue continuity and function. Collagen can act as a template for cellular activities but poor physico-chemical properties necessitates the stabilization of collagen without impairing its structure and function. This study investigates the effect of magnesium ascorbyl phosphate (MAP) on collagen with reference to physico-chemical properties. Incorporation of MAP enhanced the rate of collagen fibrillation signifying increased interaction at reduced time interval. MAP did not induce any changes in the secondary structure of collagen while there was an increase in shear viscosity with increase in shear stress at different shear rate. MAP stabilized collagen film exhibited higher denaturation temperature and showed an increase in Young's Modulus when compared with that of collagen film. In vivo studies showed complete wound closure on day 16 in case of stabilized collagen film. Mechanical properties of healed skin revealed that MAP collagen film treated rat skin completely regained its properties similar to that of normal skin thereby making them a potential candidate for wound healing application.

3 D nano bilayered spatially and functionally graded scaffold impregnated bromelain conjugated magnesium doped hydroxyapatite nanoparticle for periodontal regeneration.

Chronic periodontal disease affect the tissues supporting around the teeth like gingival tissue, connective tissue, alveolar bone and periodontal ligaments. Hitherto, periodontal treatment was targeted to selectively repopulate the defect site with cell that has capability to regenerate lost tissue by promoting the concept of guided tissue regeneration but it requires second surgery due to non- biodegradability. The use of polymeric biodegradable nanofibrous coated scaffold that have the ability to deliver bioactives required for regeneration to occur is relatively a newer concept. The functionalization of polymeric scaffold with Bromelain and magnesium doped hydroxyapatite nanoparticle enhanced the mechanical, physico-chemical, thermal and biological properties of the scaffold by imitating the intricate extracellular matrix (ECM) architecture which provided the necessary bioactive cues that offered control over cellular functions by showing antibacterial potential, hemocompatibility and increasing the proliferation and migration rate in vitro. In addition, in ovo chicken chorioallantoic membrane assay and ex vivo aortic ring assay confirmed the efficacy of the developed scaffold by encouraging angiogenesis required for maintaining its viability after implanting onto the infected area. Further, the scaffold positively interacted with the host and actively contributed to the process of tissue regeneration in vivo in Wistar rat model.

Electrospun gelatin-polyethylenimine blend nanofibrous scaffold for biomedical applications.

In this study, gelatin-polyethylenimine blend nanofibers (GEL/PEI) were fabricated via electrospinning with different ratios (9:1, 6:1, 3:1) to integrate the properties of both the polymers for evaluating its biomedical application. From scanning electron microscopy, the average diameter of blend nanofibers (265 ± 0.074 nm to 340 ± 0.088 nm) was observed to be less than GEL nanofibers (403 ± 0.08 nm). The incorporation of PEI with gelatin resulted in improved thermal stability of nanofibers whereas the Young's modulus was observed to be higher at 9:1 ratio when compared with other ratios. The in vitro studies showed that the GEL/PEI nanofibers with 9:1 ratio promoted better cell adhesion and viability. GEL/PEI nanofibers with 9:1 and 6:1 showed hemolysis within the permissible limits. From the results, it could be interpreted that GEL/PEI nanofibers with 9:1 ratio proved to be a better scaffold thereby making them a potential candidate for tissue engineering applications.

Praseodymium-Cobaltite-Reinforced Collagen as Biomimetic Scaffolds for Angiogenesis and Stem Cell Differentiation for Cutaneous Wound Healing.

The present study describes the fabrication of collagen reinforced with praseodymium-cobaltite nanoparticles for wound healing applications. Praseodymium-cobaltite nanoparticles (PCNP) reinforced with collagen resulted in an increased thermal stability and decreased proteolytic susceptibility to collagen. Circular dichroism spectroscopy and ATR-FTIR (attenuated total reflection Fourier transform infrared) spectroscopy analyses confirm the intact structural integrity of the collagen sheets after cross-linking with praseodymium-cobaltite nanoparticles. Cross-linked collagen has shown to possess biocompatibility, less protein adsorption behavior, and hemocompatibility, which are the desirable properties of a wound dressing material. The nanoparticle cross-linked collagen sheets provided a proper matrix elasticity that promotes mesenchymal stem cell attachment and angiogenesis. Further, the scaffold promoted tube formation in endothelial cells. The enhancement of angiogenesis is considered to be brought about by the therapeutic potential of nanoparticle formulation. Praseodymium-cobaltite nanoparticle cross-linking increased the ductility of collagen sheets for the pro-angiogenic and stem cell differentiation ability. Also, the praseodymium-cobaltite cross-linked collagen sheets have been shown to induce a mild level of ROS (reactive oxygen species) generation in the DCFH-DA (2',7'-dichlorodihydrofluorescein diacetate) assay, which is beneficial for angiogenesis as well as wound healing. This study paves the way for exploring the therapeutic potential of rare-earth-based nanoparticles for tissue engineering applications as an alternative for traditional wound healing materials.

Nanoscaled Biodegradable Metal-Polymeric Three-Dimensional Framework for Endothelial Cell Patterning and Sustained Angiogenesis.

The current work describes the development of a nanoscaled biodegradable metal polymeric three-dimensional framework with controlled nanotherapeutic release for endothelial cell patterning and sustained angiogenesis for biomedical applications. Biocompatible polymers gelatin and PLGA were used as polymeric nanofibrous three-dimensional framework in a core-shell manner with the gelatin core containing a biodegradable and bioactive metal nanoframework of cobalt caged with PEGylated curcumin by coaxial electrospinning. FTIR results confirmed the presence of nanobioactives in the core region of a coaxial nanofiber. Scanning electron microscopic analysis of the coaxial nanofibrous system showed a three-dimensional architecture that favored endothelial cell adhesion, patterning, migration, and proliferation. The as-synthesized nanoscaled biodegradable metal polymeric three-dimensional core-shell nanofibers exhibited potent antibacterial efficacy. Further, it improved the endothelial cell patterning promoting angiogenesis. The high therapeutic potential of cobalt nanoframework in the nanofibers enhanced the production of vascular endothelial growth factor promoting angiogenesis that resulted in the earlier restoration of wounded tissue compared with untreated control in vivo animal models. The study opens up a new horizon in exploring biodegradable biosorbable metal nanoframework for biomaterial applications. Additionally, the present study opens up a new strategy in developing biodegradable biosorbable biomaterial with enhanced vascularization efficacy to the biomaterial, which is important for acceptance of these biomaterials into the host tissue.

Fabrication of plumbagin on silver nanoframework for tunable redox modulation: Implications for therapeutic angiogenesis.

The redox state of the endothelial cells plays a key role in the regulation of the angiogenic process. The modulation of the redox state of endothelial cells (ECs) could be a viable target to alter angiogenic response. In the present work, we synthesized a redox modulator by caging 5-hydroxy 2-methyl 1, 4-napthoquinone (Plumbagin) on silver nano framework (PCSN) for tunable reactive oxygen species (ROS) inductive property and tested its role in ECs during angiogenic response in physiological and stimulated conditions. In physiological conditions, the redox modulators induced the angiogenic response by establishing ECs cell-cell contact in tube formation model, chorio allontoic membrane, and aortic ring model. The molecular mechanism of angiogenic response was induced by vascular endothelial growth factor receptor 2 (VEGFR2)/p42-mitogen-activated protein kinase signaling pathway. Under stimulation, by mimicking tumor angiogenic conditions it induced cytotoxicity by generation of excessive ROS and inhibited the angiogenic response by the loss of spatiotemporal regulation of matrix metalloproteases, which prevents the tubular network formation in ECs and poly-ADP ribose modification of VEGF. The mechanism of opposing effects of PCSN was due to modulation of PKM2 enzyme activity, which increased the EC sensitivity to ROS and inhibited EC survival in stimulated condition. In normal conditions, the endogenous reactive states of NOX4 enzyme helped the EC survival. The results indicated that a threshold ROS level exists in ECs that promote angiogenesis and any significant enhancement in its level by redox modulator inhibits angiogenesis. The study provides the cues for the development of redox-based therapeutic molecules to cure the disease-associated aberrant angiogenesis.

Strategic design of cardiac mimetic core-shell nanofibrous scaffold impregnated with Salvianolic acid B and Magnesium l-ascorbic acid 2 phosphate for myoblast differentiation.

The major loss of myocardial tissue extracellular matrix after infarction is a serious complication that leads to heart failure. Regeneration and integration of damaged cardiac tissue is challenging since the functional restoration of the injured myocardium is an incredible task. The injured micro environment of myocardium fails to regenerate spontaneously. The emergence of nano-biomaterials would be a promising approach to regenerate such a damaged cardiomyocytes tissue. Here, we have fabricated a dual bioactive embedded nanofibrous cardiac patch via coaxial electrospinning technique, to mimic the topographical and chemical cues of the natural cardiac tissue. The proportion and the concentration of the polymers were optimized for tailored delivery of bioactives from a spatio-temporally designed scaffold. The functionalization of polymeric core shell nanofibrous scaffold with dual bioactives enhanced the physico-chemical and bio-mechanical properties of the scaffolds that has resulted in a 3-dimensional topography mimicking the natural cardiac like extracellular matrix. The sustained delivery of bioactive signals, improved cell adhesion, proliferation, migration and differentiation could be attributed to its highly interconnected nanofibrous matrix with good extended morphology. Further, the expression of cardiac specific markers were found to increase on investigation of mRNA by real time PCR studies and proteins by immunofluorescence and western blotting techniques, confirming cell - biomaterial interactions. Flow cytometry analysis authenticated a potent mitochondrial membrane potential of cells treated with nanocomposite. In addition, in ovo studies in chicken chorioallantoic membrane assay confirm the efficacy of the developed scaffold in inducing angiogenesis required for maintaining its viability after transplantation onto the infarcted zone. These promising results demonstrate the potential of the composite nanofibrous scaffold as an effective biomaterial substrate for cardiac regeneration providing cues for development of novel cardiac therapeutics.

Selectivity and sensitivity of molybdenum oxide-polycaprolactone nanofiber composites on skin cancer: Preliminary in-vitro and in-vivo implications.

Cancer nanomedicine has emerged as a revolution in the last decade opening up promising strides for the cancer treatment. The major challenge in these therapeutic approaches resides in the failure of clinical trials owing to the immunological cancer microenvironment. Therefore, the success of next generation nanomedicine depends on tunable physicochemical nanomaterial design and corresponding clinical trials by integrating targeted delivery with mitigated toxicity. The present study deals with the fabrication of nanofibrous scaffold impregnated with molybdenum nanoparticles for targeted skin cancer therapeutics. Molybdenum oxide, a transitional metal oxide is gaining rapid importance due to its vital role in cellular and molecular metabolism. Polycaprolactone nanofibers were chosen as a matrix to localize the nanoparticles topically facilitating selective apoptosis of the tumor cells over the normal cells with mitigated side effects. The scaffold was designed to tailor the physicochemical, mechanical and biological suitability for skin cancer (melanoma and non melanoma). The designed scaffold was found to reduce more than 50% cell viability of the cancer cells selectively through apoptosis as confirmed using AO/PI staining and the probable mechanism could be attributed to the induction of mitochondria dependent apoptosis as observed by JC1 dye staining. In-vivo trials in zebra fish were found to reduce cancer progression by more than 30% in 14 days. The fabricated molybdenum trioxide nano constructs not only serve as tunable targeted systems but also open venues capable of ferrying chemotherapeutic drugs sparing normal cells alleviating the trauma due to side effects.

Metabolic pathway and role of individual species in the bacterial consortium for biodegradation of azo dye: A biocalorimetric investigation.

In this study, an attempt was made to investigate the functional role and metabolic behaviour of the monoculture (Staphylococcus lentus (SL), Bacillus flexus (BF) and Pseudomonas aeruginosa (PA)) in the bacterial biocenosis for biotransformation of an azo dye. The power-time profile obtained from consortia depicted three distinct peaks, which correlated well with the individual bacterial growth (PA > SL > BF), indicating the synergistic relation and division of labour in the biocenosis. The heat release pattern was used to identify the sequential behaviour of microbial consortia in real time. Yield calculation based on total heat liberated to the complete substrate utilization Y (Q/S) for PA, SL, and BF were 15.99, 16.68, 7.32 kJ/L respectively. Similarly, the oxy calorific values Y (Q/O) for the above species are respectively 386, 375, 440 kJ/mol and indicates the aerobic nature of microorganism employed. Further, the metabolome produced during the biotransformation were identified using Gas Chromatography-Mass Spectrometry (GC-MS), based on which a plausible pathway was predicted. The abundant metabolites were palmitic acid (m/z = 256) and diethyl phthalate (m/z = 222.2). The abundance of diethyl phthalate was much lesser in the consortia compared to the monoculture. Thus, the biocalorimetric heat yield calculation along with the stoichiometry and plausible pathway based biochemical elucidation provides a mechanistic basis for understanding the azo-dye biotransformation by the monocultures in consortia.

Fabrication of core-shell nanofibers for controlled delivery of bromelain and salvianolic acid B for skin regeneration in wound therapeutics.

The physiological and pathological complexity of the wound healing process makes it more challenging to design an ideal tissue regeneration scaffold. Precise scaffolding with high drug loading efficiency, efficient intracellular efficacy for therapeutic delivery, minimal nonspecific cellular and blood protein binding, and maximum biocompatibility forms the basis for an ideal delivery system. This paper describes a combinational multiphasic delivery system, where biomolecules are delivered through the fabrication of coaxial electrospinning of different biocompatible polymers. The ratio and specificity of polymers for specific biofunction are optimized and the delivery system is completely characterized with reference to the mechanical property and structural integrity of bromelain (debridement enzyme) and salvianolic acid B (pro-angiogenesis and re-epithelialization). The in vitro release profile illustrated the sustained release of debriding protease and bioactive component in a timely fashion. The fabricated scaffold showed angiogenic potential through in vitro migration of endothelial cells and increased new capillaries from the existing blood vessel in response to an in ovo chicken chorioallantoic membrane assay. In addition, in vivo studies confirm the efficacy of the fabricated scaffold. Our results therefore open up a new avenue for designing a bioactive combinational multiphasic delivery system to enhance wound healing.

Fabrication of Hybrid Collagen Aerogels Reinforced with Wheat Grass Bioactives as Instructive Scaffolds for Collagen Turnover and Angiogenesis for Wound Healing Applications.

The present study illustrates the progress of the wheat grass bioactive-reinforced collagen-based aerogel system as an instructive scaffold for collagen turnover and angiogenesis for wound healing applications. The reinforcement of wheat grass bioactives in collagen resulted in the design and development of aerogels with enhanced physicochemical and biomechanical properties due to the intermolecular interaction between the active growth factors of wheat grass and collagen fibril. Differential scanning calorimetry analysis revealed an enhanced denaturation temperature when compared to those of native collagen aerogels. Fourier transform infrared spectroscopy analysis confirmed that the reinforcement of bioactives in the wheat grass did not affect the structural integrity of the collagen molecule. Additionally, the reinforced biomaterial with a systematic absorptive morphology resulted in a three-dimensional (3D) sponge-like aerogel exhibiting a potent highly oriented 3D structural assembly that showed increased water retention ability and substance permeability that would enable the passage of nutrients and gaseous components for cellular growth. Furthermore, the cumulative effect of the growth factors in wheat grass and the collagen molecule augments the angiogenic ability and collagen production of the aerogel by restoration of the damaged tissue thereby making it a potential 3D wound dressing scaffold. The results were confirmed by in vivo wound healing assays. This study shows the possibility for progress of a biocompatible, biodegradable, and nonadhesive nutraceutical-reinforced collagen aerogel as an instructive scaffold with good antimicrobial properties for collagen turnover and angiogenic response for wound healing applications.

Curcumin cross-linked collagen aerogels with controlled anti-proteolytic and pro-angiogenic efficacy.

This paper elucidates the development of a curcumin cross-linked collagen aerogel system with controlled anti-proteolytic activity and pro-angiogenic efficacy. The results of this study showed that in situ cross-linking of curcumin with collagen leads to the development of aerogels with enhanced physical and mechanical properties. The integrity of collagen after cross-linking with curcumin was studied via FTIR spectroscopy. The results confirmed that the cross-linking with curcumin did not induce any structural changes in the collagen. The curcumin cross-linked collagen aerogels exhibited potent anti-proteolytic and anti-microbial activity. Scanning electron and atomic force microscopic analysis of curcumin cross-linked collagen aerogels showed a 3D microstructure that enhanced the adhesion and proliferation of cells. The highly organized geometry of collagen-curcumin aerogels enhanced the permeability and water-retaining ability required for the diffusion of nutrients that aid cellular growth. The pro-angiogenic properties of collagen-curcumin aerogels were ascribed to the cumulative effect of the nutraceutical and the collagen molecule, which augmented the restoration of damaged tissue. Further, these aerogels exhibited controlled anti-proteolytic activity, which makes them suitable 3D scaffolds for biomedical applications. This study provides scope for the development of biocompatible and bioresorbable collagen aerogel systems that use a nutraceutical as a cross-linker for biomedical applications.

Effect of bimetallic iron:zinc nanoparticles on collagen stabilization.

The ability of metallic nanoparticles to facilitate crosslinking of collagen by binding to side chain moieties has been studied for some time. The current study is mainly focused on understanding the effect of bimetallic iron:zinc nanoparticles on the stability of collagen. The results showed that the bimetallic nanoparticle was able to efficiently stabilize collagen, which is reflected by the enhanced fibril formation kinetics, viscosity, mechanical and thermal stability of the collagen molecule crosslinked with bimetallic nanoparticles. Contrary to the inhibitory effects on these properties exhibited by individual nanoparticles, in combination as bimetallic nanoparticles they showed superior collagen crosslinking properties. It was observed that the physico-chemical properties of the individual nanoparticles drastically change when they are combined with other metal nanoparticles and these properties are entirely different from the properties they exhibit individually. Circular dichroism analysis confirmed no structural disparity in collagen despite the superior physicochemical properties suggesting the significance of bimetallic iron:zinc nanoparticle mediated crosslinking. The ability of the bimetallic iron:zinc nanoparticles to crosslink collagen molecules suggested that the bimetallic iron:zinc nanoparticles apart from their application in tissue engineering could find use in tanning of leather. Superior stabilization of collagen by bimetallic Fe:Zn nanoparticles when compared to chrome tanning therefore may reduce the amount chromium used in leather tanning process. The present study is the first report on the application of a bimetallic nanoparticle as crosslinker for stabilisation of collagen and its application as an ecofriendly tanning agent in the leather industry. This study gives new scope for the application of bimetallic nanoparticle-based strategies for the development of alternative crosslinking agents for tissue engineering applications.

Fabrication of homobifunctional crosslinker stabilized collagen for biomedical application.

Collagen biopolymer has found widespread application in the field of tissue engineering owing to its excellent tissue compatibility and negligible immunogenicity. Mechanical strength and enzymatic degradation of the collagen necessitates the physical and chemical strength enhancement. One such attempt deals with the understanding of crosslinking behaviour of EGS (ethylene glycol-bis (succinic acid N-hydroxysuccinimide ester)) with collagen to improve the physico-chemical properties. The incorporation of a crosslinker during fibril formation enhanced the thermal and mechanical stability of collagen. EGS crosslinked collagen films exhibited higher denaturation temperature (T d) and the residue left after thermogravimetric analysis was about 16 ± 5.2%. Mechanical properties determined by uniaxial tensile tests showed a threefold increase in tensile strength and Young's modulus at higher concentration (100 µM). Water uptake capacity reduced up to a moderate extent upon crosslinking which is essential for the transport of nutrients to the cells. Cell viability was found to be 100% upon treatment with 100 µM EGS whereas only 30% viability could be observed with glutaraldehyde. Rheological studies of crosslinked collagen showed an increase in shear stress and shear viscosity at 37 °C. Crosslinking with EGS resulted in the formation of a uniform fibrillar network. Trinitrobenzene sulfonate (TNBS) assay confirmed that EGS crosslinked collagen by forming a covalent interaction with ε-amino acids of collagen. The homobifunctional crosslinker used in this study enhanced the effectiveness of collagen as a biomaterial for biomedical application.

Effect of curcumin caged silver nanoparticle on collagen stabilization for biomedical applications.

The current study aims at understanding the influence of curcumin caged silver nanoparticle (CCSNP) on stability of collagen. The results indicated that curcumin caged silver nanoparticles efficiently stabilize collagen, indicated by enhanced tensile strength, fibril formation and viscosity. The tensile strength of curcumin caged silver nanoparticle cross-linked collagen and elongation at break was also found to be higher than glutaraldehyde cross-linked collagen. The physicochemical characteristics of curcumin caged nanoparticle cross-linked collagen exhibited enhanced strength. The thermal properties were also good with both thermal degradation temperature and hydrothermal stability higher than native collagen. CD analysis showed no structural disparity in spite of superior physicochemical properties suggesting the significance of curcumin caged nanoparticle mediated cross-linking. The additional enhancement in the stabilization of collagen could be attributed to multiple sites for interaction with collagen molecule provided by curcumin caged silver nanoparticles. The results of cell proliferation and anti-microbial activity assays indicated that curcumin caged silver nanoparticles promoted cell proliferation and inhibited microbial growth making it an excellent biomaterial for wound dressing application. The study opens scope for nano-biotechnological strategies for the development of alternate non-toxic cross-linking agents facilitating multiple site interaction thereby improving therapeutic values to the collagen for biomedical application.