Enzymatically triggered graphene oxide released from multifunctional carriers boosts anti-pathogenic properties for promising wound-healing applications

Abstract

Spurred by recent progress in biomaterials and therapeutics, stimulus-responsive strategies that deliver an active substance in temporal-, spatial-, and dose-controlled fashions have become achievable. Implementation of such strategies necessitates the use of bio-safe materials that are sensitive to a specific pathological incitement or that, in response to a precise stimulus, undergo hydrolytic cleavage or a change in biomolecular conformation. An innovative design of polymeric stimulus-responsive systems should controllably release a drug or degrade the drug carrier in response to specific lesion enzymes. Wound healing is a great challenge due to various hidden factors such as pathogenic infections, neurovascular diseases, excessive exudates, lack of an effective therapeutic delivery system, low cell proliferation, and cell migration. In addition, long-term use of antibiotics in chronic wound management can result in side effects and antimicrobial resistance. Novel treatments with antibacterial pharmaceuticals thus vitally need to be developed. Recently, graphene and graphene family members have emerged as shining stars among biomaterials for wound-healing applications due to their excellent bioactive properties, which can overcome limitations of current wound dressings and fulfill wound-healing requirements. Herein, we developed a feasible approach to impregnate graphene oxide (GO) into genipin-crosslinked gelatin (3GO) hydrogels to enzymatically control GO release. The developed hydrogels were characterized by chemical, physical, morphological, and cellular analyses. The results proved that the 3GO1 hydrogel is biocompatible and significantly enhanced the mechanical strength by encapsulating GO. Moreover, the rate of GO release depended on the crosslinking degree and environmental enzyme levels. Enzymatically released GO displayed uniform dispersity, retained its antibacterial activities against Staphylococcus aureus and Pseudomonas aeruginosa through sharp edges and wrapping mechanisms, and promoted human fibroblast migration. This multifunctional hydrogel we developed with antibacterial efficacy is suitable for future application as wound dressings.