3D-bioprinted hydrogel with MALAT1 exosomes for diabetic wound healing

Diabetic foot ulcer (DFU), a life-threatening complication of diabetes, poses a significant global health burden with high morbidity and mortality. Its pathogenesis involves multiple interrelated pathways. Rat bone marrow mesenchymal stem cells (BMSCs) with MALAT1 overexpression were constructed via lentiviral transfection. After extracting exosomes, they were detected by transmission electron microscope, WB and RT-qPCR. Then, BMSCs-derived exosomes overexpressing the LncRNA MALAT1 were encapsulated into a hyaluronic acid/platelet-rich plasma (HA/PRP) bioink and were 3D printed, and the biocompatibility, mechanical properties and drug release characteristics of the 3D-printed hydrogel were detected. In the diabetic foot ulcer model of SD rats, HE and Masson staining were performed, and WB and RT-qPCR experiments were used to detect indicators of inflammation, vascularization and ECM deposition. The 3D-printed hydrogel exhibited tunable mechanical properties, biomimetic ECM-like microarchitecture, and high biocompatibility, while effectively prolonging exosome stability and bioactivity. In rat diabetic foot wound model, the MALAT1 exo-hydrogel group demonstrated the highest wound healing rate (82.43 ± 1.21 %), greater than that of other groups (approximately 66 %). MALAT1 exo-hydrogel accelerated wound healing via dual angiogenic and anti-inflammatory actions: VEGF nearly doubled, TNF-α dropped to 0.24 ± 0.02 (vs 1 ± 0.05), and IL-10 rose to 3.38 ± 0.31 (vs 1 ± 0.07), concomitantly promoting ECM reconstruction. This study proposes a "sustained delivery-microenvironment remodeling" strategy, merging RNA therapeutics with advanced biomaterials, and establishes a scalable framework for chronic wound management, offering a promising avenue to address the unmet needs in DFU therapy.