Thermosensitive hydrogel loaded with concentrated growth factors promote bone repair in segmental bone defects

Yuxin Zhang; Tianchang Wang; Dahe Zhang; Jiayi Li; Xiaokun Yue; Weiqing Kong; Xiaoding Gu; Zixian Jiao; Chi Yang

doi:10.3389/fbioe.2022.1039117

Thermosensitive hydrogel loaded with concentrated growth factors promote bone repair in segmental bone defects

Front Bioeng Biotechnol. 2022 Nov 1:10:1039117. doi: 10.3389/fbioe.2022.1039117. eCollection 2022.

Authors

Yuxin Zhang^{1

2}, Tianchang Wang³, Dahe Zhang¹, Jiayi Li¹, Xiaokun Yue³, Weiqing Kong⁴, Xiaoding Gu², Zixian Jiao¹, Chi Yang¹

Affiliations

¹ Shanghai Key Laboratory of Stomatology, National Center for Stomatology, Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Jiao Tong University, Shanghai, China.
² Department of Rehabilitation Medicine, Huangpu Branch, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Abstract

Treating critical-size bone defects beyond the body's self-healing capacity is a challenging clinical task. In this study, we investigate the effect of concentrate growth factors (CGFs) loaded Poloxamer 407 hydrogel on the viability and osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs) and reconstruction of critical-size bone defects. In vitro, this CGFs-loaded thermosensitive hydrogel can significantly promote proliferation, maintain cell viability, and induce osteogenic differentiation of BMSCs by up-regulating the mineralization and alkaline phosphatase (ALP) activity, as well as gene markers, including runt-related transcription factor-2 (Runx-2), type I collagen (Col-1), osteocalcin (OCN), as well as osteopontin (OPN). In vivo, Micro-CT radiography analysis and histological detection demonstrated that the CGFs-loaded hydrogel significantly induced bone healing and reconstructed the medullary cavity structure in critical-size bone defect models. In conclusion, this strategy of transplantation of CGFs-loaded hydrogel promoted bone regeneration and prevented bone nonunion, so as to provide basis for clinical treatment for repairing critical-size bone defects.

Keywords: bone defects; bone generation; bone marrow mesenchymal stem cells; concentrate growth factor; hydrogel.