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Nanoscaled Bionic Periosteum Orchestrating the Osteogenic Microenvironment for Sequential Bone Regeneration
journal contribution
posted on 2020-08-07, 12:08 authored by Hanwen Li, Huan Wang, Jun Pan, Jiaying Li, Kai Zhang, Weifeng Duan, Huan Liang, Kangwu Chen, Dechun Geng, Qin Shi, Huilin Yang, Bin Li, Hao ChenPeriosteum
orchestrates bone repair. Previously developed artificial
periosteum was mainly focusing on materials modification to simply
enhance bone formation, but few were attempting to make the artificial
periosteum fit different bone repair stages. Here, we constructed
a functionalized periosteum, which was composed of an electrospun
scaffold grafted with leptin receptor antibody (LepR-a) and BMP2-loaded
hollow MnO2 (h-MnO2) nanoparticles through a
polydopamine (PDA)-assisted technique. The bionic periosteum showed
suitable mechanical properties and favorable biocompatibility. It
effectively recruited skeletal stem cells (SSCs) through antigen–antibody
interactions, as in in vitro cell adhesion tests,
we observed that more SSCs attached to the LepR-a-grafted periosteum
compared to the control group. In vivo, the LepR-a-grafted
periosteum covered on the cranial defect in Prx1-Cre/ERT2, -EGFP mice
recruited more Prx1-EGFP cells to the fracture site compared to control
groups at post-surgery day 3, 7, and 14. Co-staining with Sp7 indicated
that most of the recruited Prx1-EGFP cells underwent osteogenic lineage
commitment. Sustained BMP2 release from h-MnO2 promoted
osteogenesis by accelerating the osteogenic differentiation of recruited
SSCs, as demonstrated by alkaline phosphatase (ALP) and alizarin red
staining (ARS) in vitro and microcomputed tomography
(micro-CT) in vivo. Interestingly, we also observed
the growth of osteogenic coupled capillaries (CD31hiEmcnhi) in the bone repair site, which might be induced by increased
platelet-derived growth factor-BB (PDGF-BB) in the regenerative microenvironment
subsequent to SSCs’ differentiation. Taken together, the findings
from this study indicate that the multifunctionalized periosteum efficiently
recruited and motivated the SSCs in vivo and orchestrated
the osteogenic microenvironment for bone repair in a sequence manner.
Thus, the construction of the bionic periosteum to couple with natural
bone regeneration stages has been demonstrated to be effective in
facilitating bone healing.
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Sustained BMP 2 releaseSequential Bone Regeneration Perios...platelet-derived growth factor-BBcell adhesion testsleptin receptor antibodyosteogenic lineage commitmentbone regeneration stagesPDGF-BBSSCbone repair stagesh-MnO 2PDALepR-a-grafted periosteumvivoALPbionic periosteumPrx 1-EGFP cellsARSNanoscaled Bionic Periosteum Orches...CD 31 hi Emcn hibone repair site
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