High-performance silk fibroin/hyaluronic acid interpenetrating network hydrogel microneedles for diabetes management

• Published in: International journal of biological macromolecules Vol. 298; p. 140357
• Main Authors: Hua, Jiahui, Huang, Renyan, Yu, Meng, You, Renchuan, Wang, Lu, Yan, Shuqin, Huang, Ying, Zhang, Qiang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2025
• Subjects: Animals; biocompatibility; Biodevice; Blood Glucose; Cell Survival - drug effects; cell viability; crosslinking; Diabetes; diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; fibroins; Fibroins - chemistry; glucose tolerance; Human Umbilical Vein Endothelial Cells; Humans; hyaluronic acid; Hyaluronic Acid - chemistry; hydrogels; Hydrogels - chemistry; Insulin - administration & dosage; Insulin - pharmacology; Interpenetrating network; Mice; Microneedles; Needles; Silk fibroin; therapeutics; Interpenetrating network; Biodevice; Silk fibroin; Microneedles; Diabetes
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2025.140357

Hydrogel microneedles (MNs) gained more attentions for diabetes treatments owing to their biocompatibility and versatility. However, the inherent fragility and instability of hydrogels pose limitations on their efficacy in biomedical applications. To overcome this limitation, we developed interpenetrating network hydrogels (IPNs) by incorporating silk fibroin (SF) and methacrylated hyaluronic acid (HAMA). These hydrogels exhibit rapid formation, structural stability, mechanical robustness, and sustainability through photo-crosslinking without the need for crosslinking agents. The hydrogels demonstrated an average formation time of 86 ± 8 s and exhibited favorable elasticity, along with a high compressive stress at break of 70.9 ± 8.2 kPa. Additionally, the extensive proliferation and well-distributed network of human umbilical vein endothelial cells (hUVECs) on the microneedles' (MNs) surface underscored the high cytocompatibility and cell viability of the MNs. In a diabetic mouse model, the MNs were able to maintain normal blood glucose levels for approximately 6 h. The administration of insulin-loaded microneedles to diabetic mice resulted in glucose tolerance levels comparable to those of non-diabetic mice, indicating the efficacy of microneedle therapy in improving the glycemic condition of diabetic subjects. These hydrogel MNs possess a stable structure, can be rapidly fabricated, are sustainable, and hold significant potential for the clinical management of patients with diabetes mellitus. •The catalytic effect of photo-cross-linking was employed to efficiently and expeditiously fabricate silk fibroin/hyaluronic acid (SF/HA) hydrogel microneedles.•The HA network served to suppress the adverse self-assembly of SF macromolecules, resulting in notable characteristics of the microneedles.•The interpenetrating network architecture enhanced stability of the insulin release in the hydrogels.•The effectiveness of the hydrogel microneedles in blood glucose regulation was confirmed through diabetic mice, which hold great potential for the treatment of diabetes.