Atorvastatin-Infused Carboxymethyl Cellulose-Gelatin Hydrogel: A Synergistic Strategy for Enhanced Wound Healing and Skin Tissue Regeneration.

Skin tissue engineering is an innovative alternative to traditional methods for addressing skin injuries. The aim of this study is to synthesize a hydrogel consisting of carboxymethyl cellulose (CMC) and gelatin (Gel) containing atorvastatin (ATR), which has the potential to accelerate tissue regeneration and wound healing in an animal model. Five unique formulations of hydrogel with different concentrations of ATR (0.1%, 0.5%, 1%, and 2% w/v) were synthesized using CMC-Gel. The structural characteristics of hydrogels were assessed using Scanning Electron Microscope (SEM) and Fourier-Transform Infrared (FTIR) Spectroscopy. They were assessed for swelling behavior, degradability, ATR release, compatibility, hemolytic activity, and their toxic effects on the cell viability of NIH-3T3 fibroblasts. Their therapeutic effectiveness in enhancing wound healing was also investigated in an animal model by making a full-thickness skin incision in Wistar rats. The synthesized CMC-Gel scaffolds had a porous structure with interconnected pores measuring 103±8.74 μm with the ability to enhance cell migration. The MTT analysis showed that there was a dose-dependent relationship between atorvastatin and cell proliferation, and its desirable concentration was 0.1% w/v. Furthermore, increased ATR concentrations were associated with decreased dressing's capacity for hemostasis and coagulation. In vivo studies revealed that the all hydrogel-treated groups significantly outperformed the gas-treated control group in promoting wound closure rates. Remarkably, the CMC-Gel-ATR 0.1% group exhibited the highest rates of wound closure, re-epithelialization, and angiogenesis. Our results demonstrated that CMC-Gel-ATR may be proposed as a desirable wound dressing for clinical application due to its unique physicochemical properties and comprehensive biocompatibility in an in-vitro and in-vivo investigations.