Localized trans-browning and pro-angiogenesis inductive self-assembled collagen resveratrol bio-matrix for tissue repair and regeneration in obese conditions.

The present study probes into the complexities of wound management in obesity by proposing a novel biomaterial designed to reprogram the altered skin physiology prevalent in obese conditions. The strategy involves the development of a multifunctional biomaterial addressing issues such as excessive exudate, pressure ulcers, and reduced vascularity. The bio-matrix demonstrates the localized transformation of white adipocytes through trans-browning, coupled with the simultaneous induction of angiogenesis at obese wound sites, resulting in expedited wound closure. The collagen bio-matrices, stabilized with Resveratrol (Rsv), exhibit remarkable thermal, mechanical, and biological stability. The porous 3D microstructure of the Rsv-stabilized collagen bio-matrix closely resembled the natural extracellular matrix, facilitating effective cell adhesion. The bio-matrix exhibited the unique capability to induce localized thermogenesis in the subcutaneous fat layer while concurrently activating angiogenesis. In vivo wound healing studies conducted on DIO-C57BL6 mice demonstrated complete healing within 10 days, showcasing accelerated tissue regeneration, blood vessel formation, robust collagen deposition, and significant activation of browning in the subcutaneous adipose layer. This study introduces the concept of tailored regenerative biomaterials with the ability to reprogram the challenging wound environment associated with obesity. This innovative approach opens up new avenues for enhanced wound care strategies, particularly for bariatric patients.

Apigenin Self-Assembled Collagen Biomatrix for Reprogramming the Obese Wound Microenvironment for Its Management and Repair.

Wound management in obesity is complicated by excessive exudates from wounded areas, pressure ulcerations due to stacking of the fat layer, and vascular rarefaction. The current study explored the development of biomaterials for reprogramming the altered wound microenvironment under obese conditions. Self-assembled collagen biomatrix with trans and de novo browning activator, apigenin, was fabricated as a soft tissue regenerative wound dressing material. The as-synthesized self-assembled collagen biomatrix exhibited excellent thermal, mechanical, and biological stability with a superior wound exudate absorption capacity. The apigenin self-assembled collagen biomatrix exhibited porous 3-D microstructure that mimicked the extracellular matrix that promoted cell adhesion and proliferation. The apigenin self-assembled collagen multifunctional biomatrix triggered adaptive localized thermogenesis in the subcutaneous fat layer, resulting in the activation of angiogenesis and fibroblast spreading and migration. The in vivo wound healing assay performed in DIO-C57BL6 mice showed faster tissue regeneration within 9 days, with well-defined neo-epidermis, blood vessel formation, thick collagen deposition, minimal inflammation, and significant activation of browning in the subcutaneous adipose layer. This study paves the way forward for the development of specialized regenerative biomatrices that reprogram the obese wound bed for faster tissue regeneration.

Microwave-assisted synthesis of crosslinked ureido chitosan for hemostatic applications.

In this study, we present a facile method for introducing hydrophilic ureido groups (NH2-CO-NH-) into chitosan using a microwave-assisted reaction with molten urea, with the aim of enhancing chitosan's interaction with blood components for improved hemostasis. The formation of the ureido groups through nucleophilic addition reaction between the amine groups in chitosan and in situ generated isocyanic acid was confirmed by FTIR, CP/TOSS 13C NMR, and CP/MAS 15N NMR spectroscopic techniques. However, in stark contrast to the glucans, the said modification introduced extensive crosslinking in chitosan. Spectroscopic studies identified these crosslinks as carbamate bridges (-NH-COO-), which were likely formed by the reaction between the ureido groups and hydroxyl groups of adjacent chains through an isocyanate intermediate. These carbamate bridges improved ureido chitosan's environmental stability, making it particularly resistant to changes in pH and temperature. In comparison to chitosan, the crosslinked ureido chitosan synthesized here exhibited good biocompatibility and cell adhesion, rapidly arrested the bleeding in a punctured artery with minimal hemolysis, and induced early activation and aggregation of platelets. These properties render it an invaluable material for applications in hemostasis, particularly in scenarios that necessitate stability against pH variations and degradation.

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.

Caffeine-reinforced Collagen as Localized Microenvironmental Trans-Browning Bio-Matrix for Soft Tissue Repair and Regeneration in Bariatric Condition.

The wound exudates, hypoperfusion of the subcutaneous fat layer, and poor vasculature worsen wound management in obese subjects. In the current study, a multifunctional Caffeine-reinforced collagen biomaterial is developed that can simultaneously modulate lipid metabolism and angiogenesis in obese wound microenvironments for faster tissue regeneration. The biomaterial is fabricated specialized for obese conditions to initiate simultaneous lipolysis and angiogenesis locally in the hypoxic subcutaneous fat in wound margins of obese subjects. Caffeine-reinforced collagen biomatrix shows better structural integrity, thermal stability, bio-compatibility, and lesser proteolytic susceptibility. Caffeine-collagen biomaterial promote angiogenesis, fibroblast migration, and localized browning of white adipocytes to activate thermogenesis in the subcutaneous fat layer at the wound site. Full-thickness excision wound healing studies performed in obese C57BL6 mice shows faster wound closure within day 9 when compare to control mice. The Caffeine-reinforced collagen biomaterial remodeled the wound site locally by activating fibroblast to secrete collagen, activate endothelial cells to promote angiogenesis, and induce browning in white adipocytes in subcutaneous fat. The study opens a new direction in bariatric tissue regenerative medicine by locally modulating lipid metabolism, angiogenesis, and trans-browning at the injured site for faster complete restoration of the damaged tissue.

Modulation of angiogenic switch in reprogramming browning and lipid metabolism in white adipocytes.

Thermogenic activation via trans-and de novo browning of white adipocytes is a promising strategy to accelerate lipid metabolism for regulating obesity-related disorders. In this study, we investigated the intricate interplay between angiogenic regulation and browning in white adipocytes using the bioactive compound, resveratrol (Rsv). Rsv has previously been documented for its regulatory influence on the trans and de novo browning of white adipocytes. Our findings revealed that concurrent activation of angiogenesis is prerequisite for inducing browning within the microenvironment of white adipocytes when exposed to browning activators. Additionally, we observed a significant browning effect on white adipocytes when the local adipose tissue environment was prompted to undergo angiogenesis, notably facilitated by a proangiogenic molecule known as Vascular endothelial growth factor (VEGF). Intriguingly, this effect was reversed when angiogenesis was inhibited by treatment with the antiangiogenic agent thalidomide. Furthermore, the study revealed the role of VEGF in paracrine activation of white adipocytes resulting in the induction of browning in both 3T3-L1 cell lines and primary mouse white adipocytes. The cross-talk between angiogenesis and browning was found to be initiated via the transcriptional activation of Estrogen receptor α (ERα) triggering the VEGF/VEGFR2 signaling pathway leading to browning and a reconfiguration of lipid metabolism within adipocytes. In conclusion, this study sheds light on the intricate cross-talk between angiogenesis and browning of white adipocytes. Notably, the findings underscore the reciprocal relationship between these processes, wherein inhibition of one process exerts discernible effects on the other.

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.

Hybrid nanostructured gadolinium oxide-collagen-dextran polymeric hydrogel for corneal repair and regeneration.

A bio composite hydrogel containing collagen, dextran and rare earth metal nanoparticle, gadolinium oxide nanoparticle was prepared for corneal tissue regenerative application. Gadolinium oxide nanoparticles which are widely used in MRI scanning application are not much explored for tissue regenerative applications. The synthesized nanoparticles provided stability and therapeutic potential to collagen-dextran composite for achieving tissue regenerative potential. A good compatibility towards rabbit corneal fibroblast cells (SIRC) was observed with the hydrogel along with anti-proliferation property in aortic explants. The hydrogel down-regulated the VEGF-A gene expression in endothelial cells showing its ability to safe-guard the vision from corneal neovascularization. The expression of genes, ALDH1A1 and Vimentin needed for the well-being and enhanced proliferation of corneal cells was up-regulated upon treatment with the bio composite, while the expression of pro-inflammatory cytokines IL-6 and COX-2 was down regulated. Faster regeneration and migration of corneal cells into abrasion area was observed with the bio composite in vitro. The explant studies confirmed the compatibility of bio composites towards corneal tissue as well as lens crystallin proteins. The results suggest the potential use of rare-earth metal nanoparticles-based bio composite biomaterials in repairing and regenerating corneal cells when used in combination with protein- polysaccharide biomacromolecules.

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.

Modular mucopolysaccharide gelatin naturapolyceutics hydrocolloid biomatrix with cobalt nano-additives for high density vascular network assembly.

The present study demonstrates the development of polysaccharide gelatin naturapolyceutics hydrocolloidal biomatrix with cobalt nano-additives for restructuring native tissue vasculature for tissue regenerative applications. The engineered Gelatin/Aloevera mucilage polysaccharide/nanoscaled Cobalt (GAC) hydrocolloids resulted from the intermolecular interactions between the aloevera mucilage, cobalt nano-therapeutic and gelatin. GAC hydrocolloid showed enhanced thermal stability in comparison with control Gelatin/Aloevera mucilage (GA) hydrocolloid. FTIR analysis validated that the reinforcement of aloevera mucilage and cobalt nano-therapeutic did not affect the structural integrity of the gelatin molecule. 3-Dimensional sponge-like orientation of GAC hydrocolloid facilitates perfusable biomatrix for access to nutrients and gaseous exchange for high cell adhesion and proliferation. The combined therapeutic efficacy of mucilage polysaccharides, biodegradable nanoscaled cobalt and bio-polymer enhanced the pro-angiogenic capability of the hydrocolloids by stimulating Vascular Endothelial Growth Factor (VEGF) response at wounded tissue for faster healing. The experimental outcomes on in vivo angiogenesis profiling further confirmed the development of micro vessel in chick embryonic model and regeneration of blood vessels in zebra fish model. This study opens up the potential of mucilage polysaccharides in stimulating high density angiogenesis and conveys the progress of a biocompatible, biodegradable mucilaginous hydrocolloid as an effective bio-adhesive for vascular development in soft tissue regeneration.

Rationally designed Shewanella oneidensis Biofilm Toilored Graphene-Magnetite Hybrid Nanobiocomposite as Reusable Living Functional Nanomaterial for Effective Removal of Trivalent Chromium.

Sustainable treatment of wastewater containing trivalent chromium (Cr3+) remains a significant challenge owing to the several limitations of the existing methodologies. Herein, combination of biosynthesis and Response Surface Methodology (RSM) for the fabrication and optimization of Shewanella oneidensis biofilm functionalized graphene-magnetite (GrM) nanobiocomposite was adopted as a 'living functional nanomaterial' (viz. S-GrM) for effective removal of Cr3+ ions from aqueous solution. In the biosynthetic process, S. oneidensis cells reduced the GO-akaganeite complex and adhered on the as-synthesized GrM nanocomposite to form S-GrM hybrid-nanobiocomposite. The process parameters for fabrication of S-GrM hybrid-nanobiocomposite was optimized by RSM based on four responses of easy magnetic separation, biofilm formation along with protein, and carbohydrate contents in extracellular polymeric substances (EPS). The morphology and chemical composition of S-GrM hybrid-nanobiocomposite were investigated using various spectroscopic and microscopic analyses and subsequently explored for removal of Cr3+ ions. The hybrid-nanobiocomposite effectively removed 304.64 ± 14.02 mg/g of Cr3+ at pH 7.0 and 30 °C, which is found to be very high compared to the previously reported values. The high surface area of graphene, biofilm biomass of S. oneidensis and plenty of functional groups provided a unique structure to the S-GrM hybrid-nanobiocomposite for efficient removal of Cr3+ through synergistic interaction. The FTIR and zeta potential studies confirmed that electrostatic and chelation/complexation reaction played key roles in the adsorption process. The fabrication of S-GrM nanobiocomposite thus creates a novel hybrid 'living functional nanomaterial' for low cost, recyclable, and sustainable removal of Cr3+ from wastewater.

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 juglone functionalized silver nanoparticle stabilized collagen scaffolds for pro-wound healing activities.

The effective wound management strategies depends on identification and manipulation of the molecular defects in the pathophysiology of wound. Poor vascularization, protease susceptibility and microbial invasion at wound site affect the early wound closure. Hence, an efficient wound dressing material needs to promote angiogenesis, control proteolytic activity and microbial attack. The present study, describes designing and developing a novel wound dressing material by stabilization of collagen with juglone functionalized silver nanoparticle. Stabilization of collagen with juglone functionalized silver nanoparticles enhanced thermal properties, influenced the uniform alignment of collagen fibrils which enhanced collagen's ability to promote cell proliferation. FTIR and CD analyses revealed that juglone functionalized silver nanoparticles did not induced any structural changes in the collagen molecule. Juglone functionalized silver nanoparticles controlled the proteolytic activity in a spatio-temporal manner and elicited the angiogenic response by upregulation of cell adhesion molecules like ß catenin and VE cadherin which had promoted the cell attachment and cell-cell contact. It had also promoted the expression of angiogenic signaling molecules like VEGF and VEGFR2. Further, the in vivo studies proved that the juglone functionalized silver nanoparticles had a potential role in rapid wound closure due to the cumulative property of juglone and silver nanoparticles.

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.