Evaluating the regenerative capacity of biosynthesized nano formulated 3D scaffolds in scald burn healing

Abstract

Severely burned patients require effective regenerative measures to overcome barrier defects and risk of infection. The aim of the investigation was to evaluate the regenerative capacity of DPMSCs (dental pulp-derived mesenchymal stem cells) presented in the form of nanomaterial-enriched scaffolds for tissue regeneration. These injuries specifically need proper wound repair because third and fourth-degree burns cut deep into tissues. Regenerative solutions through mesenchymal stem cells appear very promising for tissue reconstitution. However, tissue engineering has a significant difficulty in improving cell survival and retention in target tissues since direct transplantation cannot achieve these outcomes due to low cell retention rates and cell redistribution into other organs. Therefore, the study focuses on recent advances in developing injectable hydrogels, designed to address these limitations as a three-dimensional cell culturing matrix with increased water absorption capacity in vivo. The hydrogel offers an environment that is conducive to cell adhesion and growth, which is not achieved by the stem cells and nanoparticles itself, since the nanoparticles significantly contributes to promote only biological properties. We reported a new nanocomposite hydrogel of chitosan (CHI), poly(N-isopropylacrylamide) (PNIPAm) with zinc oxide nanoparticles (ZnO). Physicochemical characterisation demonstrated successful ZnO incorporation, increased structural strength, improved thermal stability, decreased swelling and increased water retention. The in vitro results showed that the isolated cells expressed CD44, CD90 and CD105 positive surface markers of MSCs (mesenchymal stem cells) as well as the capacity of trilineage differentiation. Cytotoxicity studies showed concentration dependent viability for blank hydrogel, whereas, honey-ZnO nanocomposite hydrogel showed significantly high cell survival indicating improved biocompatibility. In vivo tests using a rat scald burn model demonstrated efficient/improved/increased wound healing in the hydrogel treated groups, in particular, when it was associated with dental pulp stem cells (DPMSCs). The analysis of the gene expression profile showed that the treatment with DPMSCs resulted in the significant reduction of several inflammatory cytokines and the elevation of TGF-β (transforming growth factor-β) and COL-1 (collagenase-1), that are possible markers of regeneration. Hypermetabolic response profiling demonstrated that the hydrogels incorporated with DPMSCs, particularly containing honey, were able to suppress systemic hypermetabolism through regulation of corticosterone levels. In summary, the honey-ZnO nanocomposite thermoresponsive hydrogel fusion with DPMSCs has good prospects for deep burn wound treatment due to its enhanced biocompatibility and amplified regeneration properties.