Inflammatory phase of bone healing initiates the regenerative healing cascade |
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Authors: | Katharina Schmidt-Bleek Hanna Schell Norma Schulz Paula Hoff Carsten Perka Frank Buttgereit Hans-Dieter Volk Jasmin Lienau Georg N Duda |
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Institution: | (1) Julius Wolff Institut and Center for Musculoskeletal Surgery, Charit? – Universit?tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany;(2) Berlin-Brandenburg Center for Regenerative Therapies, Charit? – Universit?tsmedizin Berlin, Berlin, Germany;(3) Department of Rheumatology and Clinical Immunology, Charit? – Universit?tsmedizin Berlin, Berlin, Germany;(4) Institute for Medical Immunology, Charit? – Universit?tsmedizin Berlin, Berlin, Germany; |
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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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