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

2013   Volume No 26 – pages 195-207

Title: MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects

Author: C Gao, EJ Harvey, M Chua, BP Chen, F Jiang, Y Liu, A Li, H Wang, JE Henderson

Address: Bone Engineering Labs, Research Institute-McGill University Health Centre, Surgical Research, C9.133, Montreal General Hospital, 1650 Cedar Ave, Montreal, Quebec, H3G 1A4, Canada

E-mail: janet.henderson at

Key Words: Bone repair; collagen scaffold; mesenchymal stromal cells; vascular endothelial growth factor.

Publication date: October 13th 2013

Abstract: The functional repair of large skeletal defects remains a significant challenge to orthopaedic surgeons due to the lack of effective strategies to promote bone regeneration, particularly in the elderly. This study investigated the potential use of bone marrow derived mesenchymal stromal cells (MSC) in a dense collagen scaffold with a bolus dose of vascular endothelial growth factor (VEGF) to repair a defect in the femoral diaphysis of mice. MSC isolated from bone marrow of 4-month-old donor mice were seeded in type I collagen gels that were then compressed to form scaffolds with a fibrillar density similar to osteoid. The cells remained metabolically active in scaffolds incubated in vitro for up to 15 days and differentiated into osteoblasts that deposited calcium-phosphate mineral into the scaffold, which was quantified using micro-computed tomographic (micro-CT) imaging. When implanted in a 1 mm x 3 mm unicortical defect the MSC-loaded scaffolds were rapidly mineralised and integrated into host bone with administration of 10 ng of recombinant VEGF injected into the femoral canal at 4 days postoperative. Empty scaffolds and MSC-seeded scaffolds implanted in defects that did not receive a bolus dose of VEGF did not mineralise or integrate with native bone. The approach with MSC, hydrogels and a biologic factor already approved for human use warrants further pre-clinical investigation with a large animal model.

Article download: Pages 195-207 (PDF file)
DOI: 10.22203/eCM.v026a14