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Creation of Bony Microenvironment with Extracellular Matrix Doped-Bioactive Ceramics to Enhance Osteoblast Behavior and Delivery of Aspartic Acid-Modified BMP-2 Peptides

Authors Zhou J, Xiong Z, Liu M, Yang L, Yao S, Chen K, Yu K, Qu Y, Sun T, Guo X

Received 17 July 2020

Accepted for publication 30 September 2020

Published 29 October 2020 Volume 2020:15 Pages 8465—8478

DOI https://doi.org/10.2147/IJN.S272571

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster


Jinge Zhou,1,* Zekang Xiong,1,* Man Liu,2 Liang Yang,1 Sheng Yao,1 Kaifang Chen,1 Keda Yu,1 Yanzhen Qu,1 Tingfang Sun,1 Xiaodong Guo1

1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China; 2Department of Gastroenterology and Hepatology, Taikang Tongji Hospital, Wuhan 430050, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiaodong Guo; Tingfang Sun Tel +8615327216660
; +8613554435801
Email xiaodongguo@hust.edu.cn; tingfangsun@163.com

Introduction: Decellularized matrix from porcine small intestinal submucosa (SIS) endows scaffolds with an ECM-like surface, which enhances stem cell self-renewal, proliferation, and differentiation. Mesoporous bioactive glass (MBG) is extensively recognized as an excellent bio-ceramic for fabricating bone grafts.
Materials and Methods: In the current study, SIS was doped on an MBG scaffold (MBG/SIS) using polyurethane foam templating and polydopamine chemistry method. To mimic the bony environment of a natural bone matrix, an ECM-inspired delivery system was constructed by coupling the BMP2-related peptide P28 to a heparinized MBG/SIS scaffold (MBG/SIS-H-P28). The release of P28 from MBG/SIS-H-P28 and its effects on the proliferation, viability, and osteogenic differentiation of bone marrow stromal stem cells were investigated in vitro and in vivo.
Results: Our research indicated that the novel tissue-derived ECM scaffold MBG/SIS has a hierarchical and interconnected porous architecture, and superior biomechanical properties. MBG/SIS-H-P28 released P28 in a controlled manner, with the long-term release time of 40 d. The results of in vitro experiments showed improvements in cell proliferation, cell viability, alkaline phosphatase activity, and mRNA expression levels of osteogenesis-related genes (Runx-2, OCN, OPN, and ALP) compared to those of MBG/SIS or MBG/SIS-P28 and MBG/SIS-H-P28. The in vivo results demonstrated that MBG/SIS-H-P28 scaffolds evidently increased bone formation in rat calvarial critical-sized defect compared to that in controls.
Conclusion: MBG/SIS-H-P28 scaffolds show potential as ideal platforms for delivery of P28 and for providing a bony environment for bone regeneration.

Keywords: small intestinal submucosa, mesoporous bioactive glass, microenvironment, osteogenesis, BMP2-related peptide

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