Han Sun,Qianping Guo,Chen Shi,Ross H. McWilliam,Jianquan Chen,Caihong Zhu,Fengxuan Han,Pinghui Zhou,Huilin Yang,Jinbo Liu,Xiaoliang Sun,Bin Meng,Wenmiao Shu,Bin Li
In the strategy of in situ bone regeneration , it used to be difficult to specifically recruit bone marrow mesenchymal stem cells (BM-MSCs) by a single marker. Recently, CD271 has been considered to be one of the most specific markers to isolate BM-MSCs; however, the effectiveness of CD271 antibodies in recruiting BM-MSCs has not been explored yet. In this study, we developed novel CD271 antibody-functionalized chitosan (CS) microspheres with the aid of polydopamine (PDA) coating to recruit endogenous BM-MSCs for in situ bone regeneration. The CS microspheres were sequentially modified with PDA and CD271 antibody through dopamine self-polymerization and bioconjugation , respectively. In vitro studies showed that the CD271 antibody-functionalized microspheres selectively captured significantly more BM-MSCs from a fluorescently labeled heterotypic cell population than non-functionalized controls. In addition, the PDA coating was critical for supporting stable adhesion and proliferation of the captured BM-MSCs. Effective early recruitment of CD271 + stem cells by the functionalized microspheres at bone defect site of SD rat was observed by the CD271/DAPI immunofluorescence staining, which led to significantly enhanced new bone formation in rat femoral condyle defect over long term. Together, findings from this study have demonstrated, for the first time, that the CD271 antibody-functionalized CS microspheres are promising for in situ bone regeneration.
Wenliao Chang,Peipei Lu,Shuxiang Li,Jinghua Xiang,Jiachen Liu,Yimin Wang,Lei Zhang,Han Sun
Currently, bone defects remain a major challenge in clinical treatment. Recruiting target cells at the defect site and inducing them to differentiate into bone tissue are effective treatment methods. In previous studies, we used the CD271 antibody to construct bone marrow mesenchymal stem cell (BMSC) recruitment microspheres for the treatment of bone defects. However, the osteoconductivity of the microspheres themselves was poor, and the system lacked osteoinductivity, which affected the repair efficiency. In this study, we prepared submillimeter-sized porous chitosan (CS) microspheres through process optimization, and the BMSCs were able to directly adhere and proliferate on their surfaces. After the bioconjugation of the CD271 antibody, bone morphogenetic protein-2 (BMP-2) was further loaded onto the pore structure of microspheres to obtain the injectable microspheres with BMSC recruitment and osteogenic differentiation induction functions. Microspheres could efficiently recruit BMSCs through the combined action of the CD271 antibody and BMP-2 and further induce the recruited BMSCs, differentiating into osteoblasts through BMP-2, which ultimately exhibited promising bone regeneration ability in rats. We expect that the novel functional microspheres have great potential in biomedical applications for in situ treatment of bone defects.
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