ABSTRACT
Development of scaffold from biopolymers can ease the requirements for donor skin autograft and plays an effective role in the treatment of burn wounds. In the current study, a porous foam based, bilayered hydrogel scaffold was developed using gelatin, hyaluronic acid and chondroitin sulfate (G-HA-CS). The fabricated scaffold was characterized physicochemically for pre- and post-sterilization efficacy by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA).In-vitrostudies proved that the scaffold promoted cellular proliferation. The efficacy of G-HA-CS scaffold was compared with Integra™ at different time points (7, 14, 21 and 42 days), in a swine second degree burn wound model. Remarkable healing potential of the scaffold was evident from the wound contraction rate, reduction of IL-6, TNF-αand C3. The expression of healing markers TGF-ß1 and collagen 1 revealed significant skin regeneration with regulated fibroblast activation towards the late phase of healing (p< 0.001 at day 21 and 42 vs. control). Expression of Vascular Endothelial Growth Factor A (VEGFA), vimentin and N-cadherin were found to favor angiogenesis and skin regeneration. Mechanistically, scaffold promoted wound healing by modulation of CD-45, cyclooxygenase-2 and MMP-2. Thus, the promising results with foam based scaffold, comparable to Integra™ in swine burn injury model offer an innovative lead for clinical translation for effective management of burn wound.
Subject(s)
Burns/metabolism , Chondroitin Sulfates , Hyaluronic Acid , Tissue Scaffolds/chemistry , Wound Healing/drug effects , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/pharmacology , Disease Models, Animal , Gamma Rays , Gelatin/chemistry , Gelatin/pharmacology , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Male , Porosity , SwineABSTRACT
The objective of this study was to devise a dual functionalized chitosan based hydrogel dressing to control haemorrhage/ bleeding. The haemostatic hydrogel was formulated by amalgamation of a definite ratio of quaternized chitosan and phosphorylated chitosan along with tannic acid which acted as adjuvant hemostat and a crosslinker. Additionally, the hydrogel contained poly-Æ-lysine to impart the elastic and adhesive properties. The optimized hydrogel exhibited superior haemostatic activity (clotting time, 225 ± 5 s), platelet activation (soluble P-selectin concentration 2098 ± 150.19 ng mL-1), adhesion strength (almost 3 times higher in comparison to Axiostat), higher fluid absorption (approx. 14 times in 12 h) in addition to better mechanical properties, faster coagulation attributes (Prothrombin time, 12.6 s and activated partial thromboplastin time, 30.1 s) and lower proinflammatory potential (almost 3 times lower Tumor Necrosis Factor- α levels and 45 times lower InterLeukin-6 levels at 48 h against control) over marketed chitosan based dressing (clotting time, 300 ± 25 s). Cytotoxicity studies using L929 fibroblasts cells and in-vivo studies using Wistar rats confirmed that the optimized hydrogel was non-toxic, cytocompatible and biocompatible.
ABSTRACT
In the present investigation, the potential of a novel, self-assembled, biocompatible, and redox-sensitive copolymer system with disulfide bond was explored for doxorubicin (DOX) delivery through polymersome nanostructures of â¼120 nm. The polymer system was synthesized with less steps, providing a high yield of 86%. The developed polymersomes showed admirable biocompatibility with high dose tolerability in vitro and in vivo. The colloidal stability of DOX-loaded polymersomes depicted a stable and uniform particle size over a period of 72 h. The cellular internalization of polymersomes was assessed in HeLa and MDA-MB-231 cell lines, where enhanced cellular internalization was observed. The dose-dependent cytotoxicity was observed for DOX-loaded polymersomes by MTT cytotoxicity assay in the above cell lines. The tumor suppression studies were assessed in Ehrlich ascites tumor (EAT) carrying Swiss albino mice, where polymersomes exhibited a 7.16-fold reduction in tumor volume correlated with control and 5.39-fold higher tumor inhibition capacity compared to conventional chemotherapy (free DOX treatment). The developed polymersomes gave safer insights concerning DOX associated toxicities by histopathology and serum biochemistry analysis. Thus, results focus on the potential of redox responsive polymersomes for efficacious and improved DOX therapy with enhanced antitumor activity and insignificant cardiotoxicity which can be translated to clinical settings.
