Combined Effect: Development and Physical/Biological Assessment of PVA/Chitosan Hydrogels Containing rhTGF-β1-Loaded PLGA Nanoparticles

Wound healing remains a persistent health problem with no definitive solution. It is crucial to characterize the complex wound healing process and the various growth factors, cytokines, and polypeptides involved. Transforming growth factor beta1 (rhTGF-β1) stimulates different cell types, providing multifunctionality in the wound healing process. Since proteins are sensitive to proteases, drug delivery systems are needed. Developed polymeric carrier systems are as important as the active substance. The carrier systems used in our study aim to contribute to wound healing in addition to the rhTGF-β1. We hypothesized that PLGA nanoparticles embedded in PVA/Chitosan (PVA/Chi) hydrogels could enhance the therapeutic effect of rhTGF-β1. PVA/Chitosan hydrogels were prepared by the freezing/thawing method. Several characterization studies (Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), texture analysis, and cell culture) were performed to investigate the potential of the prepared formulations to enhance the therapeutic effect of rhTGF-β1. Hydrogel formulations reduced the inhibitory effect of rhTGF-β1 on keratinocytes. The H5 hydrogel exhibited a proliferative effect on fibroblast cells, which play a crucial role in wound healing, resulting in a 78.8% increase compared to the control. As the PVA content in the hydrogel formulations increased, bioadhesion and viscosity also increased. Although TGF-β1 inhibited keratinocytes, it induced migration of both NIH-3T3 and HACAT cell lines. The formulations developed exhibit the potential to improve the therapeutic efficacy of rhTGF-β1 in wound healing. A small amount of the protein can have the same therapeutic efficacy and fewer side effects because the developed polymeric carrier systems contribute to the therapeutic efficacy.