Serial cellular events in bone formation initiated by calcium phosphate ceramics

作者全名："Guo, Xiaodong; Li, Mingzheng; Qi, Wenting; Bai, Hetian; Nie, Zhangling; Hu, Zhiqiao; Xiao, Yu; de Bruijn, Joost D.; Bao, Chongyun; Yuan, Huipin"

作者地址："[Guo, Xiaodong; Qi, Wenting; Bai, Hetian; Nie, Zhangling; Hu, Zhiqiao; Xiao, Yu; Bao, Chongyun] Sichuan Univ, State Key Lab Oral Dis, Natl Clin Res Ctr Oral Dis, West China Hosp Stomatol, 14,Sect 3,Ren Min Nan Rd, Chengdu 610041, Sichuan, Peoples R China; [Li, Mingzheng] Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn High, Stomatol Hosp, Chongqing 400015, Peoples R China; [de Bruijn, Joost D.; Yuan, Huipin] Kuros Biosci BV, Prof Bronkhorstlaan 10, NL-3723 MB Bilthoven, Netherlands; [de Bruijn, Joost D.] Queen Mary Univ London, Sch Engn & Mat Sci, London, England; [Yuan, Huipin] Huipin Yuans Lab, Chengdu, Sichuan, Peoples R China"

通信作者："Bao, CY (corresponding author), Sichuan Univ, State Key Lab Oral Dis, Natl Clin Res Ctr Oral Dis, West China Hosp Stomatol, 14,Sect 3,Ren Min Nan Rd, Chengdu 610041, Sichuan, Peoples R China.; Yuan, HP (corresponding author), Kuros Biosci BV, Prof Bronkhorstlaan 10, NL-3723 MB Bilthoven, Netherlands.; Yuan, HP (corresponding author), Huipin Yuans Lab, Chengdu, Sichuan, Peoples R China."

来源：ACTA BIOMATERIALIA

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000710094900007

JCR分区：Q1

影响因子：9.7

年份：2021

卷号：134

期号：　

开始页：730

结束页：743

文献类型：Article

关键词：Osteoinductive materials; Calcium phosphate ceramics; Macrophages; Osteoclasts; Host response

摘要："To better understand the biological mechanisms triggered by osteoinductive materials in vivo, we evalu-ated the timeline of cellular responses to osteoinductive materials subcutaneously implanted in FVB mice. More F4/80-positive macrophages were present in osteoinductive tri-CaP ceramic (TCP) with submicron surface topography (TCPs) than non-osteoinductive TCP with micron surface topography (TCPb) at week 1. Moreover, TCPs (but not TCPb) significantly enhanced osteoclastogenesis, and induced macrophages to polarize from M1 to M2 in the first week. The time sequence and relevance of macrophages and osteoclasts responses involved in bone formation was then evaluated through peri-implant injection of specific chemicals in mice implanted with osteoinductive TCPs. Day-1 injection of clodronate liposomes (LipClod) depleted macrophages, inhibited macrophage polarization to M2, blocked osteoclastogenesis and bone formation, while the day-6 injection was less effective. Anti-RANKL antibody (aRANKL) did not affect macrophage colonization but inhibited osteoclastogenesis. Injection of aRANKL before week 2 aborted bone formation in TCPs, while injection at week 4 partially inhibited bone formation. The overall data show that following ectopic implantation, osteoinductive materials allow macrophage colonization in hours to days, macrophage polarization to M2 in days (within 7 days), osteoclastogenesis in weeks (e.g. in 2 weeks) and bone formation thereafter (after 4 weeks). The serial cellular events verified herein bring a new insight on material-induced bone formation and pave the way to further explore the mechanisms triggered by osteoinductive materials. Statement of significance A series of key cellular events triggered by osteoinductive calcium phosphate ceramic was revealed: macrophages colonized within hours to days, polarization of M2 macrophages occurred within 7 days, osteoclastogenesis mainly occurred in weeks (e.g. in 2 weeks) and bone formation finally arose thereafter (after 4 weeks). Moreover, such time sequence of cellular events was confirmed with specific chemi-cals (clodronate liposomes and anti-RANKL antibody). The findings verified herein bring a new insight on material-induced bone formation and pave the way to further explore the mechanisms triggered by osteoinductive materials. (c) 2021 Published by Elsevier Ltd on behalf of Acta Materialia Inc."

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