Integrating tea nanoparticle with short peptides to generate tunable hydrogel scaffolds for diabetic ulcer

Abstract

Tea is very popular in the world owing to its numerous therapeutic effects in lowering blood pressure, decreasing blood coagulation, repairing oxidative damage among many others. Due to their promising biodegradability, biocompatibility and antimicrobial activity, tea nanoparticles isolated from tea leaves have a great potential for various biomedical applications. Small molecules like polyphenols and polysaccharides from tea exhibit anti-cancer and antioxidant properties. As the major polyphenolic compound found in tea, epigallocatechin-3-gallate (EGCG) exhibits excellent anti-oxidant and free radical-scavenging activities. The wound healing process is closely related to extensive oxidative stress to the system. Because of the strong antioxidant activities, EGCG has been proposed for wound healing by facilitating reepithelialization. Short peptides are known to be easily form self-supporting transparent hydrogel structures. Fmoc-Phe-Phe is such an intriguing peptide that it could form stable hydrogels by means of adjusting temperature and pH values during the synthesis process. The hydrogel could be transplanted to full-thick-ness wounds for the treatment of deep wounds. The hydrogel matrix could help the migration of host cells and blood vessels, as well as allow the rapid recovery of the wound and regeneration of tissues. Also, the hydrogel provides a barrier to protect the wound from the infection of microorganism. A peptide-polysaccharide hybrid hydrogel triggered by calcium ion is to be constructed. The calcium-triggered-co-assembly of Fmoc-Phe-Phe peptide and tea nanoparticle is able to self-assemble into nanofibers. The cross-link structure by the noncovalent and ionic interactions between calcium and polysaccharide in tea nanoparticle would enhance the mechanical property of hydrogel. The peptide hydrogel along with anti-inflammatory and antioxidant effects of epigallocatechin-3-gallate (EGCG) and polyphenols from tea nanoparticles could have a positive effect on wound healing. In this study, the calcium-ion-triggered co-assembly of Fmoc-Phe-Phe peptide and tea nanoparticle to form hybrid hydrogel was investigated. The morphological structure of the hybrid hydrogel was modulated by optimizing the ratio of the peptide, calcium ion and tea nanoparticle to achieve the best mechanical property for diabetic ulcer applications. We also investigated the potential of tea nanoparticle-incorporated peptide hydrogel for the treatment of wound healing in diabetic mice. Under glucose diabetic conditions EGCG had a positive effect, therefore the hybrid hydrogel with tea nanoparticle may be potentially used as a healing agent for diabetic ulcer.