3D-Printed GelMA Microneedles with Multilayer Therapeutic Properties for Diabetic Wound-Relevant Drug Delivery

Abstract Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by impaired insulin secretion, reduced insulin sensitivity, and hyperglycemia. Diabetic wounds are among the major complications of T2DM and can lead to chronic wounds due to challenges in the normal healing process. In this study, a three-layered tissue scaffold incorporating microneedles (MNs) was developed for diabetic wound management. The scaffold was fabricated using digital light processing (DLP) for the GelMA-based layers and electrohydrodynamic atomization (EHDA) for the surface coating, combining antibacterial, metabolic, and antioxidant functions within a single platform. The first two layers were designed using gelatin methacrylate (GelMA) and produced via DLP. The first layer was loaded with the antibiotic amoxicillin to prevent infection at the scaffold application site. In the second layer, MNs containing metformin were designed. For the outermost layer, polylactic acid (PLA) microparticles containing antioxidant and antibacterial salicylic acid (SA) were produced via the EHDA method and coated onto the scaffold surface. This three-layered scaffold was characterized by SEM, FT-IR, DSC, and mechanical, swelling, degradation, and penetration analyses. In vitro studies of single-drug-loaded model formulations demonstrated biphasic drug-release behavior over 72 h, effective antibacterial activity against E. coli and S. aureus, and favorable cytocompatibility. Oxidative-stress assays showed lower Total Oxidant Status (TOS) levels and higher Total Antioxidant Status (TAS) values in the drug-loaded formulations, while the scratch assay demonstrated increased wound-gap closure under hyperglycemic culture conditions. Overall, the multilayer microneedle platform exhibited antibacterial activity, with inhibition zones of up to 23 mm, and favorable cytocompatibility, with cell viability remaining above 77% across all formulations. These findings provide in vitro proof-of-concept evidence for the multifunctional design of the platform but do not demonstrate wound-healing efficacy in diabetic tissue.