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Nano-Scaled Bionic Periosteum Orchestrating Osteogenic Microenvironment for Sequential Bone Regeneration.

Han-xian Li,Huan Wang,Jun Pan,Jiaying Li,Kai Zhang,Weifeng Duan,Huan-you Liang,Kangwu Chen,D. Geng,Q. Shi,Huilin Yang,Bin Li,Hao Chen

Published 2020 in ACS Applied Materials and Interfaces

ABSTRACT

Periosteum orchestrates bone repair. Previously developed artificial periosteum was mainly focusing on materials modification to simply enhance bone formation, but few was 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 nano-particles (h-MnO2) through a polydopamine (PDA)-assisted technique. The bionic periosteum showed suitable mechanical properties and favorable biocompatibility. It effectively recruited SSCs through antigen-antibody interactions, as in vitro, cell adhesion tests, we observed more attached SSCs on 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 ALP and alizarin red staining in vitro and Micro-CT in vivo. Interestingly, we also observed osteogenic coupled capillaries (CD31hiEmcnhi) growth into the bone repair site, which might be induced by increased PDGF-BB in the regenerative microenvironment subsequent to SSCs' differentiation. Taken together, findings from this study indicate that the multi-functionalized 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 the natural bone regeneration stages has been demonstrated to be effective in facilitating bone healing.

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