Carboxymethyl cellulose-agarose hydrogel in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nanofibers: A novel tissue engineered skin graft

Abstract

Healing chronic and critical-sized full-thickness wounds is a major challenge in the healthcare sector. Scaffolds prepared using electrospinning and hydrogels serve as effective treatment options for wound healing by mimicking the native skin microenvironment. Combining synthetic nanofibers with tunable hydrogel properties can effectively overcome limitations in skin scaffolds made only with nanofibers or hydrogels. In this study, a biocompatible hybrid scaffold was developed for wound healing applications using poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers embedded with hydrogel made of 2 % carboxymethyl cellulose (CMC) blended with 1 % agarose. Hybrid scaffolds, characterized for surface morphology, swellability, porosity, and degradation, were found to be suitable for wound healing. Furthermore, the incorporation of CMC-agarose hydrogel into nanofibers significantly enhanced their mechanical strength compared to PHBV nanofibers alone (p < 0.05). Extract cytotoxicity and direct cytotoxicity tests showed that the hybrid scaffolds developed in this study are cytocompatible (>75 % viability). Furthermore, human adult dermal fibroblasts (HDFa) and human adult immortalized keratinocytes (HaCaT) adhesion, viability, and proliferation studies revealed that the hybrid scaffolds exhibited a significant increase in cell proliferation over time, similar to PHBV nanofibers. Finally, the developed hybrid scaffolds were evaluated in rat full-thickness wounds, demonstrating their ability to promote full-thickness wound healing with reepithelialization and epidermis closure.