Therapeutic hydrogel for wound healing applications

Abstract

Managing chronic wounds is a complex challenge, often aggravated by the presence of inflammation and infection. Hydrogel materials stand out for their remarkable properties such as biocompatibility and drug-loading capabilities, making them ideal for applications in wound dressing and tissue regeneration. A compelling treatment strategy involves not only resolving persistent hyperinflammation but also effectively eliminating infection. The demand for an "all-in-one" hydrogel platform with dual functions, targeting both inflammation and infection in chronic wounds, is huge in clinical settings. This thesis presents two promising dual-functional hydrogel platforms specifically crafted for potent topical application in the treatment of wounds. First platform was named "pull and push" hydrogel, which is essentially micro-sized hydrogel functionalized with innovative and versatile telodendrimers (TDs). By rational design and synthesis, these conjugated TDs can strongly grab or trap inflammatory factors such as cytokines and endotoxins, as well as hold drug payload such as antibiotics and release out in a desired manner. We demonstrated the TD hydrogel's capability to scavenge proinflammatory cytokines using in vitro assays, and shown the TD hydrogel's effect in scavenging cytokines in a mouse model with skin inflammation. We also demonstrated TD hydrogel's structure dependent capabilities in encapsulating different antibiotics, and sustainable release profile. The drug maintained its efficacy with prolonged therapeutic window and reduced toxicity, as evidenced by in vitro assays and in vivo animal skin and soft tissue infection model. Second hydrogel platform was termed "kill and block", which is essentially a bulky photo-crosslinked hydrogel incorporated with telodendrimer nano-formulated antibiotics. Nanodrug released from topically applied bulky photogel can further dissociate into drug and nanocarrier telodendrimer. The released drug functions as antimicrobial to "kill" bacteria. Dead bacteria still potentially stimulate inflammation. The payload-free nanocarrier can simultaneously modulate local immune response by "blocking" inflammatory pathway. In addition, this platform address issues of wound morphology adaptiveness. We demonstrated the tunable drug release profiles, reserved drug efficacy after TD encapsulation and phtogel incorporation, and superior anti-inflammation efficacy in vitro and in vivo. Collectively, we organically combined the advantages of nanotechnology and hydrogel platform, providing promising solutions for the chronic wound treatment from immune modulation and drug delivery.