Layered GelMA/PEGDA Hydrogel Microneedle Patch as an Intradermal Delivery System for Hypertrophic Scar Treatment

Hypertrophic scar (HS) is an unfavorable skin disorder that typically develops after trauma, burn injury, or surgical procedures and causes numerous physical and psychological issues in patients. Currently, intralesional multi-injection of corticosteroid, particularly compound betamethasone (CB), is one of the most prevalent treatments for HS. However, injection administration could result in severe pain and dose-related side effects. Additionally, the vacuum therapeutic efficacy of this treatment relies on the level of expertise of the healthcare professional. To overcome the limitations of conventional injections, a new method that is convenient, painless, and self-administrable is urgently required. In this study, we developed a methacrylate gelatin (GelMA)/polyethylene glycol diacrylate (PEGDA) double-network hydrogel microneedle patch loaded with CB (CB-HMNP) as an intradermal delivery system for HS treatment. The double-network structure conferred the CB-HMNP with sufficient mechanical properties to successfully penetrate scar tissue while also helping to regulate the drug's sustained release rate. Subsequently, we confirmed that the CB-HMNP had a pronounced inhibitory effect on human HS fibroblasts (hHSFs), whereas drug-free HMNPs had no effect on hHSFs, indicating its high biocompatibility. In order to assess the therapeutic efficacy of CB-HMNPs, HS models of New Zealand rabbit ears were developed. The administration of CB-HMNP three times significantly decreased the scar elevation index (SEI), collagen I/III, and transforming growth factor-β1 (TGF-β1) protein. Therefore, the CB-HMNP may offer an administration pathway for the treatment of HS that is less painful, more convenient, less invasive, and sustain-released.