Early osteoimmunomodulation by mucin hydrogels augments the healing and revascularization of rat critical-size calvarial bone defects

Song Chen; Huan Wang; Dachuan Liu; Jianzhong Bai; Håvard Jostein Haugen; Bin Li; Hongji Yan

doi:10.1016/j.bioactmat.2023.01.022

Early osteoimmunomodulation by mucin hydrogels augments the healing and revascularization of rat critical-size calvarial bone defects

Bioact Mater. 2023 Feb 4:25:176-188. doi: 10.1016/j.bioactmat.2023.01.022. eCollection 2023 Jul.

Authors

Song Chen¹, Huan Wang¹, Dachuan Liu¹, Jianzhong Bai¹, Håvard Jostein Haugen², Bin Li¹, Hongji Yan^{3

4

5}

Affiliations

¹ Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
² Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, PO Box 1109 Blindern, Oslo, 0376, Norway.
³ AIMES - Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institute and KTH Royal Institute of Technology, 171 77, Stockholm, Sweden.
⁴ Department of Neuroscience, Karolinska Institute, 171 77, Stockholm, Sweden.
⁵ Division of Glycoscience, Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, AlbaNova University Center, 106 91, Stockholm, Sweden.

Abstract

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 in vivo. 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.

Keywords: Bone; Monetite; Mucin hydrogels; Revascularization; osteoimmunomodulation.