Bisphosphonate-based hydrogel mediates biomimetic negative feedback regulation of osteoclastic activity to promote bone regeneration

Bioactive Materials

Zhengmeng Yang¹  Xian Xie²  Gang Li²  Boguang Yang³  Peng Shi⁴  Zhuo Li⁴  Lingchi Kong⁴  Kunyu Zhang⁵  Yi-Ping Ho⁶  Haixing Wang⁷  Yuan Zhang⁷  Zhi-Yong Zhang⁸  Liming Bian⁸ 

[1] Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, 510006, China;National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, China;School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, 510006, China;Department of Biomedical Engineering, The Chinese University of Hong Kong, Sha Tin, New Territories, 999077, Hong Kong, China;Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA;Department of Orthopaedic Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, China;Department of Orthopaedic and Traumatology, The Chinese University of Hong Kong, Sha Tin, New Territories, 999077, Hong Kong, China;School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, 510006, China;

关键词: Bisphosphonate;    Hydrogel;    Tissue engineering;    Bone regeneration;   

DOI  :  

来源: DOAJ

【 摘 要 】

The intricate dynamic feedback mechanisms involved in bone homeostasis provide valuable inspiration for the design of smart biomaterial scaffolds to enhance in situ bone regeneration. In this work, we assembled a biomimetic hyaluronic acid nanocomposite hydrogel (HA-BP hydrogel) by coordination bonds with bisphosphonates (BPs), which are antiosteoclastic drugs. The HA-BP hydrogel exhibited expedited release of the loaded BP in response to an acidic environment. Our in vitro studies showed that the HA-BP hydrogel inhibits mature osteoclastic differentiation of macrophage-like RAW264.7 cells via the released BP. Furthermore, the HA-BP hydrogel can support the initial differentiation of primary macrophages to preosteoclasts, which are considered essential during bone regeneration, whereas further differentiation to mature osteoclasts is effectively inhibited by the HA-BP hydrogel via the released BP. The in vivo evaluation showed that the HA-BP hydrogel can enhance the in situ regeneration of bone. Our work demonstrates a promising strategy to design biomimetic biomaterial scaffolds capable of regulating bone homeostasis to promote bone regeneration.

【 授权许可】

Unknown