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Inflammatory phase of bone healing initiates the regenerative healing cascade

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Abstract

Bone healing commences with an inflammatory reaction which initiates the regenerative healing process leading in the end to reconstitution of bone. An unbalanced immune reaction during this early bone healing phase is hypothesized to disturb the healing cascade in a way that delays bone healing and jeopardizes the successful healing outcome. The immune cell composition and expression pattern of angiogenic factors were investigated in a sheep bone osteotomy model and compared to a mechanically-induced impaired/delayed bone healing group. In the impaired/delayed healing group, significantly higher T cell percentages were present in the bone hematoma and the bone marrow adjacent to the osteotomy gap when compared to the normal healing group. This was mirrored in the higher cytotoxic T cell percentage detected under delayed bone healing conditions indicating longer pro-inflammatory processes. The highly activated periosteum adjourning the osteotomy gap showed lower expression of hematopoietic stem cell markers and angiogenic factors such as heme oxygenase and vascular endothelial growth factor. This indicates a deferred revascularization of the injured area due to ongoing pro-inflammatory processes in the delayed healing group. Results from this study suggest that there are unfavorable immune cells and factors participating in the initial healing phase. In conclusion, identifying beneficial aspects may lead to promising therapeutical approaches that might benefit further by eliminating the unfavorable factors.

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Acknowledgements

The authors would like to thank Dr. Bettina Willie for helping in editing this manuscript.

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Correspondence to Georg N. Duda.

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This study was supported by a grant from the German Research Foundation (DFG SFB 760). No benefit of any kind has been or will be received either directly or indirectly by the authors.

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Schmidt-Bleek, K., Schell, H., Schulz, N. et al. Inflammatory phase of bone healing initiates the regenerative healing cascade. Cell Tissue Res 347, 567–573 (2012). https://doi.org/10.1007/s00441-011-1205-7

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