occurrence and treatment of bone atrophic non-unions investigated by an integrative approach萎缩性骨不愈合的发生和治疗研究的综合方法.pdfVIP

Occurrence and Treatment of Bone Atrophic Non-Unions Investigated by an Integrative Approach 1,2,3. 4,5. 1 6 Liesbet Geris *, Anita A. C. Reed , Jos Vander Sloten , A. Hamish R. W. Simpson , Hans Van Oosterwyck1,2 1 Division of Biomechanics and Engineering Design, Department of Mechanical Engineering, Katholieke Universiteit Leuven, Leuven, Belgium, 2 Prometheus, Division of ` ` Skeletal Tissue Engineering, Katholieke Universiteit Leuven, Leuven, Belgium, 3 Biomechanics Research Unit, University of Liege, Liege, Belgium, 4 Nuffield Department of Orthopaedic Surgery, University of Oxford, Oxford, United Kingdom, 5 Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom, 6 Department of Trauma Orthopaedics, Edinburgh University, Edinburgh, United Kingdom Abstract Recently developed atrophic non-union models are a good representation of the clinical situation in which many non- unions develop. Based on previous experimental studies with these atrophic non-union models, it was hypothesized that in order to obtain successful fracture healing, blood vessels, growth factors, and (proliferative) precursor cells all need to be present in the callus at the same time. This study uses a combined in vivo-in silico approach to investigate these different aspects (vasculature, growth factors, cell proliferation). The mathematical model, initially developed for the study of normal fracture healing, is able to capture essential aspects of the in vivo atrophic non-union model despite a number of deviations that are mainly due to simplifications in the in silico model. The mathematica