Multi-Omics-Informed Hydrogel:Il-6 Reduce Endoplasmic Reticulum Stress

Aim or purpose: Post - traumatic bone healing demonstrates remarkable heterogeneity, particularly in diverse injury sites. Significantly, alveolar bone defects exhibit a more rapid healing progression compared to the relatively slower repair process witnessed in femoral bone. Considering this physiological phenomenon, discerning site - specific differences is pivotal for the design of functional biomaterials to augment bone regeneration. Materials and methods: Through comprehensive multi - omics analysis, this research pinpointed the crucial function of M2 macrophages that highly express interleukin - 6 (IL - 6) during the early stage of alveolar bone healing. It was discovered that the IL - 6 concentration within M2 macrophages had the capacity to regulate heat shock protein family A member 5. By doing so, it mitigated endoplasmic reticulum stress (ERS) and inhibited apoptosis, consequently facilitating bone regeneration. Results: In light of these discoveries, a porous hydrogel formulated from gelatin was further designed and optimized for the local delivery of IL - 6 to hasten the process of bone healing in femoral defects. Experimental results indicated that this hydrogel effectively enhanced the regeneration of femoral bone. It achieved this by regulating the endoplasmic reticulum stress response and the body's reaction to hematoma, thus facilitating a more efficient bone - repair mechanism. Conclusions: These results present potentially viable strategies to boost bone regeneration.