Triple-molded, reinforced arrowhead microneedle patch of dual human-derived matrix for integrated management of diabetic wounds

Abstract

Platelet-rich plasma (PRP) is often administered with gauze for wound management clinically. However, this treatment method suffers from poor contact, drug wastage and limited delivery depth compromising therapeutic efficacy. Local injections address some of these challenges but are invasive and cause significant pain. In response, we develop a transdermal delivery system utilizing type 1 recombinant human collagen (1-RHC) to integrate PRP within a hydrogel microneedle patch (MNP). The reaction of methacrylic anhydride with 1-RHC yields methacrylate RHC (1-RHCMA), which when combined with PRP, self-assembles into an arrow-shaped MNP, 1-RHCMA-PRP Arrow-MNP (RPAM) via a triple-molding process. The 1-RHCMA-PRP hydrogel demonstrates pro-epithelial, pro-angiogenesis, anti-inflammatory, and antibacterial properties in vitro. When applied to rat diabetic wound models, RPAM also regulates collagen alignment and demonstrates robust mechanical properties which can prevent pathological scar formation by stabilizing the wound bed. Transcriptome sequencing further confirms that RPAM promotes excellent healing via pro-keratinization and modulation of immune response. Additionally, RPAM exhibits no toxicity to any organs within the organism, mitigating any immunogenic concerns. Herein, our RPAM dual-derived from PRP and 1-RHCMA can manage wound complications with minimal invasiveness and excellent wound closure, offering significant potential for clinical translation.

Keywords: Diabetic wound; Microneedle patch; Platelet-rich plasma; Recombinant human collagen; Skin regeneration.