Multi-omics-informed hydrogel design: modulating IL-6 to reduce endoplasmic reticulum stress in bone regeneration.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41141587.
- Also identified by DOI 10.1016/j.bioactmat.2025.09.005 and PMC identifier 12553026.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Post-traumatic bone healing exhibits significant heterogeneity, especially in different injury sites. Notably, bone healing progresses more rapidly in alveolar bone defects compared to the slower repair process observed in femoral bone. Given this physiological phenomenon, understanding site-specific differences is crucial for designing functional biomaterials to enhance bone regeneration. This study, via multi-omics analysis, identified the pivotal role of high interleukin-6 (IL-6) expressing alternatively activated (M2) macrophages in early alveolar bone healing. It was found that IL-6 level in M2 macrophages could modulate heat shock protein family A member 5, alleviating endoplasmic reticulum stress (ERS) and preventing apoptosis, thereby promoting bone regeneration. Based on these findings, a gelatin-based porous hydrogel optimized for localized IL-6 delivery was further developed to accelerate bone healing in femoral defects. The results demonstrated that this hydrogel significantly enhanced femoral bone regeneration by modulating ERS and hematoma responses. These findings offer promising strategies for enhancing bone regeneration.