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

2014   Volume No 28 – pages 166-208

Title: Tissue engineered bone using select growth factors: A comprehensive review of animal studies and clinical translation studies in man

Author: D Gothard, EL Smith, JM Kanczler, H Rashidi, O Qutachi, J Henstock, M Rotherham, A El Haj, KM Shakesheff, ROC Oreffo

Address: Bone and Joint Research Group, Human Development and Health, University of Southampton, School of Medicine, Institute of Developmental Sciences, Mail Point 887, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK

E-mail: D.Gothard at or richard.oreffo at

Key Words: Animal model, bone tissue engineering, BMP-2, BMP-7, clinical translation, FGF, human studies, in vivo, OP-1, PDGF, PTH, PTHrP, TGF-β3, VEGF, Wnt proteins.

Publication date: October 6th 2014

Abstract: There is a growing socio-economic need for effective strategies to repair damaged bone resulting from disease, trauma and surgical intervention. Bone tissue engineering has received substantial investment over the last few decades as a result. A multitude of studies have sought to examine the efficacy of multiple growth factors, delivery systems and biomaterials within in vivo animal models for the repair of critical-sized bone defects. Defect repair requires recapitulation of in vivo signalling cascades, including osteogenesis, chondrogenesis and angiogenesis, in an orchestrated spatiotemporal manner. Strategies to drive parallel, synergistic and consecutive signalling of factors including BMP-2, BMP-7/OP-1, FGF, PDGF, PTH, PTHrP, TGF-β3, VEGF and Wnts have demonstrated improved bone healing within animal models. Enhanced bone repair has also been demonstrated in the clinic following European Medicines Agency and Food and Drug Administration approval of BMP-2, BMP-7/OP-1, PDGF, PTH and PTHrP. The current review assesses the in vivo and clinical data surrounding the application of growth factors for bone regeneration. This review has examined data published between 1965 and 2013. All bone tissue engineering studies investigating in vivo response of the growth factors listed above, or combinations thereof, utilising animal models or human trials were included. All studies were compiled from PubMed-NCBI using search terms including ‘growth factor name’, ‘in vivo’, ‘model/animal’, ‘human’, and ‘bone tissue engineering’. Focus is drawn to the in vivo success of osteoinductive growth factors incorporated within material implants both in animals and humans, and identifies the unmet challenges within the skeletal regenerative area.

Article download: Pages 166-208 (PDF file)
DOI: 10.22203/eCM.v028a13

Supplementary Tables 1-9 (PDF file)