Localized delivery of metformin via 3D printed GelMA-Nanoclay hydrogel scaffold for enhanced treatment of diabetic bone defects.

Background: Diabetic bone defects present significant challenges for individuals with diabetes. While metformin has been explored for bone regeneration via local delivery, its application in treating diabetic bone defects remains under-explored. In this study, we aim to leverage 3D printing technology to fabricate a GelMA-Nanoclay hydrogel scaffold loaded with metformin specifically for this purpose. The objective is to assess whether the in situ release of metformin can effectively enhance osteogenesis, angiogenesis, and immunomodulation in the context of diabetic bone defects. Materials and methods: Utilizing 3D printing technology, we constructed a GelMA-Nanoclay-Metformin hydrogel scaffold with optimal physical properties and biocompatibility. The osteogenic, angiogenic, and immunomodulatory characteristics of the hydrogel scaffold were thoroughly investigated through both in vitro and in vivo experiments. Results: GelMA10%-Nanoclay8%-Metformin5mg/mL was selected as the bioink for 3D printing due to its favorable swelling rate, degradation rate, mechanical strength, and drug release rate. Through in vitro investigations, the hydrogel scaffold extract, enriched with metformin, demonstrated a substantial enhancement in the proliferation and migration of BMSCs within a high-glucose microenvironment. It effectively enhances osteogenesis, angiogenesis, and immunomodulation. In vivo experimental outcomes further underscored the efficacy of the metformin-loaded GelMA-Nanoclay hydrogel scaffold in promoting superior bone regeneration within diabetic bone defects. Conclusions: In conclusion, while previous studies have explored local delivery of metformin for bone regeneration, our research is pioneering in its application to diabetic bone defects using a 3D printed GelMA-Nanoclay hydrogel scaffold. This localized delivery approach demonstrates significant potential for enhancing bone regeneration in diabetic patients, offering a novel approach for treating diabetic bone defects. The translational potential of this article: Our study demonstrates, for the first time, the successful loading of the systemic antidiabetic drug metformin onto a hydrogel scaffold for localized delivery. This approach exhibits significant efficacy in mending diabetic bone defects, presenting a promising new avenue for the treatment of such conditions.