Physically Cross-Linked DNA Hydrogel-Based Sustained Cytokine Delivery for In Situ Diabetic Alveolar Bone Rebuilding

The development of a biodegradable and shape-adaptable bioscaffold that can enhance local cytokine retention and bioactivity is essential for the application of immunotherapy in periodontal diseases. Here, we report a biodegradable, anti-inflammatory, and osteogenic ILGel that uses a physically cross-linked DNA hydrogel as a soft bioscaffold for the long-term sustained release of cytokine interleukin-10 (IL-10) to accelerate diabetic alveolar bone rebuilding. Porous microstructures of ILGel favored the encapsulation of IL-10 and maintained IL-10 bioactivity for at least 7 days. ILGel can be gradually degraded or hydrolyzed under physiological conditions, avoiding the potential undesired side effects on dental tissues. Long-term sustained release of bioactive IL-10 from ILGel not only promoted M2 macrophage polarization and attenuated periodontal inflammation but also triggered osteogenesis of mesenchymal stem cells (MSCs), leading to accelerated alveolar bone formation and healing of alveolar bone defects under diabetic conditions in vivo. ILGel treatment significantly accelerated the defect healing rate of diabetic alveolar injury up to 93.42 ± 4.6% on day 21 post treatment compared to that of free IL-10 treatment (63.30 ± 7.39%), with improved trabecular architectures. Our findings imply the potential application of the DNA hydrogel as the bioscaffold for cytokine-based immunotherapy in diabetic alveolar bone injury and other periodontal diseases.