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

Authors
Seyed-Reza Mousavi 1
Mojtaba Rashidi 2
Azam Khedri 1
Maryam Kouchak 3
Majid Salehi 4
Sepehr Zamani 5
Ghorban Mohammadzadeh 2
1 Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 Hyperlipidemia Research Center, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Department of Pharmaceutics, Faculty of Pharmacy, Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4 Regenerative Medicine Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
5 Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
10.61882/ibj.5043
Abstract
Background: Skin tissue engineering is an innovative alternative to traditional methods for addressing skin injuries. This study aimed to synthesize a hydrogel consisting of carboxymethyl cellulose (CMC) and gelatin (Gel) containing atorvastatin (ATR) with the potential to accelerate tissue regeneration and wound healing in an animal model.

Methods: 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 the hydrogels were assessed using SEM and FTIR spectroscopy. Additional evaluations carried out included swelling behavior, degradability, ATR release, compatibility, hemolytic activity, and the viability of NIH/3T3 fibroblast cells. The therapeutic effectiveness of these hydrogels in enhancing wound healing was investigated in an animal model by making a full-thickness skin incision in Wistar rats.

Results: The synthesized CMC-Gel scaffolds had a porous structure with interconnected pores measuring 103 ± 8.74 μm and the ability to enhance cell migration. The MTT analysis showed a concentration-dependent relationship between ATR and cell proliferation, among which, the desirable concentration was 0.1% w/v. Furthermore, increased ATR concentrations were associated with decreased dressing capacity for hemostasis and coagulation. In vivo studies revealed that all the hydrogel-treated groups significantly outperformed the 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.

Conclusion: Our results suggest the CMC-Gel-ATR as a desirable wound dressing for clinical application due to its unique physicochemical properties and comprehensive biocompatibility in in vitro and in vivo investigations.
Keywords
Angiogenesis
Atorvastatin
biopolymers