biostudies-literatureChen SNorges ForskningsrådMajor Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education InstitutionsPriority Academic Program Development of Jiangsu Higher Education InstitutionsNational Natural Science Foundation of ChinaNatural Science Research of Jiangsu Higher Education Institutions of ChinaStiftelsen för Strategisk Forskning176-188https://www.ebi.ac.uk/biostudies/studies/S-EPMC9932297biostudies-literatureUnknown25The design principle of osteogenic bone grafts has shifted from immunological inertness to limiting foreign body response to combined osteoimmunomodulatory activity to promote high-quality endogenous bone regeneration. Recently developed immunomodulatory mucin hydrogels have been shown to elicit very low complement activation and suppress macrophage release and activation after implantation <i>in vivo</i>. However, their immunoregulatory activity has not yet been studied in the context of tissue repair. Herein, we synthesized mucin-monetite composite materials and investigated their early osteoimmunomodulation using a critical-size rat bone defect model. We demonstrated that the composites can polarize macrophages towards the M2 phenotype at weeks 1 and 2. The early osteoimmunomodulation enhanced early osteogenesis and angiogenesis and ultimately promoted fracture healing and engraftment (revascularization of the host vasculature) at weeks 6 and 12. Overall, we demonstrated the applicability of mucin-based immunomodulatory biomaterials to enhance tissue repair in tissue engineering and regenerative medicine.Bioactive materialsEarly osteoimmunomodulation by mucin hydrogels augments the healing and revascularization of rat critical-size calvarial bone defects.PMC993229720KJB430041819250273227142182002275331752FFL15-0072Haugen HJWang HBai JLi BChen SLiu DYan HfalseEarly osteoimmunomodulation by mucin hydrogels augments the healing and revascularization of rat critical-size calvarial bone defects.The design principle of osteogenic bone grafts has shifted from immunological inertness to limiting foreign body response to combined osteoimmunomodulatory activity to promote high-quality endogenous bone regeneration. Recently developed immunomodulatory mucin hydrogels have been shown to elicit very low complement activation and suppress macrophage release and activation after implantation <i>in vivo</i>. However, their immunoregulatory activity has not yet been studied in the context of tissue repair. Herein, we synthesized mucin-monetite composite materials and investigated their early osteoimmunomodulation using a critical-size rat bone defect model. We demonstrated that the composites can polarize macrophages towards the M2 phenotype at weeks 1 and 2. The early osteoimmunomodulation enhanced early osteogenesis and angiogenesis and ultimately promoted fracture healing and engraftment (revascularization of the host vasculature) at weeks 6 and 12. Overall, we demonstrated the applicability of mucin-based immunomodulatory biomaterials to enhance tissue repair in tissue engineering and regenerative medicine.2023-01-01T00:00:00Z2023 Jul2025-04-26T22:23:23.639Z2025-04-06T17:08:03.536ZS-EPMC99322973681782510.1016/j.bioactmat.2023.01.022