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

Zhuo Li; Haixing Wang; Kunyu Zhang; Boguang Yang; Xian Xie; Zhengmeng Yang; Lingchi Kong; Peng Shi; Yuan Zhang; Yi-Ping Ho; Zhi-Yong Zhang; Gang Li; Liming Bian

doi:10.1016/j.bioactmat.2021.11.004

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

Bioact Mater. 2021 Nov 12:13:9-22. doi: 10.1016/j.bioactmat.2021.11.004. eCollection 2022 Jul.

Authors

Zhuo Li¹, Haixing Wang², Kunyu Zhang^{3

4

5

6}, Boguang Yang¹, Xian Xie¹, Zhengmeng Yang², Lingchi Kong⁷, Peng Shi^{4

5}, Yuan Zhang^{4

5}, Yi-Ping Ho¹, Zhi-Yong Zhang⁸, Gang Li², Liming Bian^{4

5

6}

Affiliations

¹ Department of Biomedical Engineering, The Chinese University of Hong Kong, Sha Tin, New Territories, 999077, Hong Kong, China.
² Department of Orthopaedic and Traumatology, The Chinese University of Hong Kong, Sha Tin, New Territories, 999077, Hong Kong, China.
³ Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
⁴ School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, 510006, China.
⁵ National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, China.
⁶ Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, 510006, China.
⁷ Department of Orthopaedic Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, China.
⁸ Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, 510150, China.

Abstract

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.

Keywords: Bisphosphonate; Bone regeneration; Hydrogel; Tissue engineering.