eCM (Eur Cell Mater / e Cells & Materials) Not-for-Profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2018   Volume No 36 – pages 69-80

Title: Osteogenic extracellular matrix sheet for bone tissue regeneration

Authors: T Onishi, T Shimizu, M Akahane, S Omokawa, A Okuda, T Kira, Y Inagak, Y Tanaka

Address: Department of Orthopaedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan

E-mail: tk-shimi at

Abstract: The application of extracellular matrix (ECM) sheets without a scaffold is not extensively reported in bone regenerative medicine. The aim of the present study was to demonstrate that an osteogenic ECM sheet (OECMS) can retain ECM integrity and growth factors to enhance bone formation in a rat non-union model. OECMS was produced from osteogenic cell sheets (OCS). Collagen and growth factor [bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factors (VFGFs), basic fibroblast growth factor (bFGF) and transforming growth factor β1 (TGF-β1)] concentrations in the OECMS were quantified by enzyme-linked immunosorbent assay (ELISA). Next, hydroxyapatite (HA) constructs combined with OECMSs were implanted subcutaneously into the rats' backs to evaluate their osteoinductive capacity by histological evaluation. In addition, OECMSs were implanted in a rat femoral non-union model. 18 male Fischer 344 inbred rats were divided into OECMS and control groups. Fracture healing was evaluated by radiological and histological analyses at 2, 5 and 8 weeks and biological analysis at 8 weeks. Collagen I and growth factors were retained in the OECMSs. Osteoid formation was identified in the HA combined with OECMS at 4 weeks. Enhanced bone regeneration at the non-union of the OECMS group was confirmed at 5 and 8 weeks. Biomechanical testing revealed a significantly higher maximum bending load in the OECMS group as compared to the control group at 8 weeks. The results demonstrated that OECMS retained BMP-2 and TGF-β1 and high osteoinductive and osteoconductive capacity. As such, OECMS represents a potential new scaffold-free material for bone tissue engineering.

Key Words: Extracellular matrix, cell sheet, osteoinductive capacity, osteoconductive capacity, bone regeneration, non-union model.

Publication date: August 2nd 2018

Article download: Pages 69-80 (PDF file)

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