Induced periosteum a complex cellular scaffold for the treatment of large bone defects.

OBJECTIVE: Surgically induced periosteal membrane holds great potential for the treatment of large bone defects representing a simple alternative to combinations of exogenous stem cells, scaffolds and growth factors. The purpose of this study was to explore the biological basis for this novel regenerative medicine strategy in man. METHODS: Eight patients with critical size defects were treated with the induced membrane (IM) technique. After membrane formation 1cm(2) biopsy was taken together with matched, healthy diaphyseal periosteum (P) for comparative analysis. Morphological characteristics, cell composition and growth factor expression were compared. Functional and molecular evaluation of mesenchymal stromal cell (MSC) activity was performed. RESULTS: Both tissues shared similar morphology although IM was significantly thicker than P (p=0.032). The frequency of lymphocytes, pericytes (CD45(-)CD34(-)CD146(+)) and cells expressing markers consistent with bone marrow MSCs (CD45(-/low)CD271(bright)) were 31. 3 and 15.5-fold higher respectively in IM (all p=0.043). IM contained 3-fold more cells per gramme of tissue with a similar proportion of endothelial cells (CD45(-)CD31(+)). Expressed bone morphogenic protein 2, vascular endothelial growth factor and stromal derived factor 1 (SDF-1) are key tissue regeneration mediators. Adherent expanded cells from both tissues had molecular profiles similar to bone marrow MSCs but cells from IM expressed greater than 2 fold relative abundance of SDF-1transcript compared to P (p=0.043). CONCLUSION: The IM is a thick, vascularised structure that resembles periosteum with a cellular composition and molecular profile facilitating large defect repair and therefore may be described as an "induced-periosteum". This tissue offers a powerful example of in situ tissue engineering.