Retracted Article: Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils

Tao Li; Hongtao He; Zezheng Yang; Junjie Wang; Yuxin Zhang; Guangxu He; Jun Huang; Deye Song; Jiangdong Ni; Xiaojun Zhou; Junfeng Zhu; Muliang Ding

doi:10.1039/D0BM02126A

Retracted Article: Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils†

Tao Li,‡^ab Hongtao He,‡^c Zezheng Yang,‡^d Junjie Wang,^a Yuxin Zhang,^e Guangxu He,^a Jun Huang,^a Deye Song,^a Jiangdong Ni,^a Xiaojun Zhou,*^f Junfeng Zhu*^b and Muliang Ding

*^a

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* Corresponding authors

^a Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
E-mail: dingmuliang@csu.edu.cn
Fax: +86 (21) 23271698
Tel: +86 15800577039

^b Department of Orthopaedics, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai, P. R. China
E-mail: zhujunfeng@xinhuamed.com.cn

^c The Third Ward of Department of Orthopedics, The Second Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian, Liaoning Province 116000, P. R. China

^d Department of Orthopedics, The Fifth People's Hospital of Shanghai, Fudan University, Minhang District, Shanghai 200240, P. R. China

^e Department of Rehabilitation Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Huangpu District, Shanghai 200011, China

^f College of Chemistry, Chemical Engineering and Biotechnology; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, P. R. China
E-mail: xjz362@163.com

Abstract

The immune system mediates inflammation, vascularization and the first response to injuries or implanted biomaterials. Although the function of neutrophils in tissue repair has been extensively studied, its complete role in the tissue regeneration of biomaterials, specifically the resolution of inflammation and promotion of angiogenesis, is unclear. Here, we fabricate nanofibrous gelatin scaffolds containing 10% (w/w) strontium-hydroxyapatite (SrHA) via phase-separation methods to investigate Sr-mediated regulation of neutrophil polarization and, subsequently, the effects on angiogenesis and macrophage polarization. Compared with neutrophils cultured on pure gelatin or HA-incorporated gelatin scaffolds, neutrophils on SrHA-incorporated gelatin scaffolds show more N2 polarization in vitro and in vivo and significantly greater production of immunomodulatory and angiogenic factors. The Sr-induced immunomodulatory and proangiogenic functions of neutrophils are mediated through NF-κB pathway downregulation and increased STAT3 phosphorylation. Thus, neutrophils play a vital role in tissue engineering, and Sr-incorporated scaffolds efficiently promote neutrophil polarization to the N2 phenotype, enhancing resolution of inflammation and ultimately promoting angiogenesis and tissue regeneration. Thus, incorporation of neutrophils in analyses of the immune characteristics of scaffolds and the development of immunomodulatory biomaterials that can regulate neutrophils are novel and promising strategies in tissue engineering.

Biomaterials Science

Retracted Article: Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils†

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