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Predictors of fracture healing in patients with recalcitrant nonunions treated with autologous culture expanded bone marrow-derived mesenchymal stromal cells.

Kuiper

Predictors of fracture healing in patients with recalcitrant nonunions treated with autologous culture expanded bone marrow-derived mesenchymal stromal cells. Thumbnail


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Abstract

The study reports the prospective outcome of treating severe recalcitrant fracture nonunion in patients with autologous bone marrow-derived mesenchymal stromal cells (BMSC) from 2003 to 2010 and analyze predictors of union. Autologous BMSC were culture expanded and inserted at nonunion site with or without carriers in addition to surgical stabilization of the fracture. Radiological union was ascertained by musculoskeletal radiologists on plain radiographs and/or CT scans. A logistic regression analysis was performed with cell-expansion parameters (cell numbers, cell doubling time) and known clinical factors (e.g., smoking and diabetes) as independent variables and fracture union as the dependent variable to identify the factors that influence bony healing. An Eq5D index score assessed the effect of treatment on general quality of health. A total of 35 patients (mean age 51+/-13 years) with established nonunion (median 2.9 years, 1-33) and, at least one failed nonunion surgery (median 4,1-14) received treatment. Fracture union was achieved in 21 patients (60%; 95%CI 44-75) at 2.6 years. Multiple penalized logistic regression revealed faster cell doubling time (p?=?0.07), absence of diabetes (p?=?0.003), less previous surgeries (p?=?0.008), and lower age at cell implantation (p?=?0.02) were significant predictors for fracture union. A significant increase in Eq5D index (p?=?0.01) was noted with a mean rise of the score by 0.34 units (95%CI 0.11-0.58) at 1 year following the study. In summary, the study revealed cell doubling time as a novel in vitro parameter in conjunction with age, multiple surgeries, and diabetes as being significant predictors of the fracture union. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. J Orthop Res.

Acceptance Date Nov 26, 2018
Publication Date Jun 1, 2019
Publicly Available Date Mar 28, 2024
Journal Journal of Orthopaedic Research
Print ISSN 0736-0266
Publisher Wiley
Pages 1303-1309
DOI https://doi.org/10.1002/jor.24184
Keywords bone; biomaterials; progenitors and stem cells; bone biology; bone tissues engineering and repair; bone fracture
Publisher URL https://onlinelibrary.wiley.com/doi/full/10.1002/jor.24184

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