Carboxymethyl cellulose/sodium alginate hydrogel with anti-inflammatory capabilities for accelerated wound healing; In vitro and in vivo study

Abstract

Recently, managing the chronic skin wounds has become increasingly challenging for healthcare professionals due to the intricate orchestration of cellular and molecular processes involved that lead to the uncontrollable inflammatory reactions which hinder the healing process. Therefore, different types of wound dressings with immunomodulatory properties have been developed in recent years to effectively regulate the immune responses, enhance angiogenesis, promote re-epithelialization, and accelerate the wound healing process. This study aims to develop a new type of immunomodulatory wound dressing utilizing carboxymethyl cellulose (CMC)/sodium alginate (Alg)-simvastatin (SIM) to simultaneously enhance the inflammatory responses and the wound healing ratio. The CMC/Alg-SIM hydrogels exhibited appropriate swelling ratio, water vapor transmission rate, and desirable degradation rate, depending on the SIM content. The fabricated dressing showed sustained release of SIM (during 5 days) that improved the proliferation of skin cells. According to the in vitro findings, the CMC/Alg-SIM hydrogel exhibited controlled pro-inflammatory responses (decreased 2.5- and 1.6-times IL-6 and TNF-alpha, respectively) and improved secretion of anti-inflammatory cytokines (increased 1.5- and 1.3-times IL-10 and TGF-beta, respectively) in comparison with CMC/Alg. Furthermore, the CMC/Alg-SIM hydrogel facilitated rapid wound healing in the rat model with a full-thickness skin defect. After 14 days post-surgery, the wound healing ratio in the CMC/Alg hydrogel group (-93%) was significantly greater than the control group (-58%). Therefore, the engineered CMC/Alg-SIM hydrogel with desired immunomodulatory properties possesses the potential to enhance and accelerate skin regeneration for the management of chronic wound healing.