Combined Strategy of Wound Healing Using Thermo-Sensitive PNIPAAm Hydrogel and CS/PVA Membranes: Development and In-Vivo Evaluation

Past studies have shown that the hot spring effect can promote wound healing. Mild thermal stimulation and metal ions can promote angiogenesis. In this study, the hot spring effect was simulated by thermosensitive PNIPAAm hydrogel loaded with copper sulfide nanoparticles. Heat stimulation could be generated through near-infrared irradiation, and copper ions solution could be pulsed. On the other hand, the CS/PVA nanofiber membrane was attached to the bottom of the hydrogel to simulate the extracellular matrix structure, thus improving the wound healing ability. The CS/PVA nanofiber membrane was prepared by electrospinning, and the appropriate prescription and process parameters were determined. The nanofiber membrane has uniform pore size, good water absorption and permeability. The poor mechanical properties of PNIPAAm hydrogel were improved by adding inorganic clay. The temperature of the hydrogel loaded with CuS nanoparticles reached 40 °C under near-infrared light irradiation for 20 min, and the release rate of Cu(2+) reached 26.89%. The wound-healing rate of the rats in the combined application group reached 79.17% at 13 days, demonstrating superior results over the other control groups. Histological analyses show improved inflammatory response at the healed wound area. These results indicate that this combined application approach represents a promising wound treatment strategy.