Transplantation Surgery and ResearchNoncultured Minimally Processed Adipose-Derived Stem Cells Improve Radiated Fracture HealingLynn, Jeremy V. BSa; Ranganathan, Kavitha MDa; Urlaub, Kevin M. BSa; Luby, Alexandra O. MSa; Stephan, Chris J. MSb; Donneys, Alexis MD, MSa; Nelson, Noah S. MPHa; Buchman, Steven R. MDaAuthor Information From the aCraniofacial Research Laboratory bOrthopedic Research Laboratory, University of Michigan, Ann Arbor, MI. Received October 27, 2019, and accepted for publication, after revision February 3, 2020. J.V.L. and K.R. contributed equally to this work. The results presented in this article were presented at the 2018 Plastic Surgery Research Council annual meeting in Birmingham, Alabama. All authors contributed to the design and execution of this study, as well as composition and refinement of this manuscript. Specifically, J.V.L. and K.R. jointly oversaw all components of work in the laboratory and wrote the first draft of the article. K.M.U., A.D., A.O.L., and N.S.N. contributed to data analysis and edited the first draft of the article. C.J.S. performed biomechanical strength testing and contributed to the corresponding sections in the Methods and Results. Finally, S.R.B. provided senior guidance and support both in the laboratory space and in the drafting and finalization of this article. All authors accept responsibility for the integrity of the data analysis. Conflicts of interest and sources of funding: The authors have nothing to disclose. This work was supported by the National Institutes of Health RO1 grants CA12587-01 and CA12587-06 awarded to S.R.B. and an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship awarded to J.V.L. Reprints: Steven R. Buchman, MD, University of Michigan, 1540 E Hospital Dr, Floor 4, Suite 4-730, Ann Arbor, MI 48104. E-mail: firstname.lastname@example.org. Annals of Plastic Surgery: July 2020 - Volume 85 - Issue 1 - p 83-88 doi: 10.1097/SAP.0000000000002354 Buy Metrics Abstract Adipose-derived stem cells mitigate deleterious effects of radiation on bone and enhance radiated fracture healing by replacing damaged cells and stimulating angiogenesis. However, adipose-derived stem cell harvest and delivery techniques must be refined to comply with the US Food and Drug Administration restrictions on implantation of cultured cells into human subjects prior to clinical translation. The purpose of this study is to demonstrate the preservation of efficacy of adipose-derived stem cells to remediate the injurious effects of radiation on fracture healing utilizing a novel harvest and delivery technique that avoids the need for cell culture. Forty-four Lewis rats were divided into 4 groups: fracture control (Fx), radiated fracture control (XFx), radiated fracture treated with cultured adipose-derived stem cells (ASC), and radiated fracture treated with noncultured minimally processed adipose-derived stem cells (MP-ASC). Excluding the Fx group, all rats received a fractionated human-equivalent dose of radiation. All groups underwent mandibular osteotomy with external fixation. Following sacrifice on postoperative day 40, union rate, mineralization, and biomechanical strength were compared between groups at P < 0.05 significance. Compared with Fx controls, the XFx group demonstrated decreased union rate (100% vs 20%), bone volume fraction (P = 0.003), and ultimate load (P < 0.001). Compared with XFx controls, the MP-ASC group tripled the union rate (20% vs 60%) and demonstrated statistically significant increases in both bone volume fraction (P = 0.005) and ultimate load (P = 0.025). Compared with the MP-ASC group, the ASC group showed increased union rate (60% vs 100%) and no significant difference in bone volume fraction (P = 0.936) and ultimate load (P = 0.202). Noncultured minimally processed adipose-derived stem cells demonstrate the capacity to improve irradiated fracture healing without the need for cell proliferation in culture. Further refinement of the cell harvest and delivery techniques demonstrated in this report will enhance the ability of noncultured minimally processed adipose-derived stem cells to improve union rate and bone quality, thereby optimizing clinical translation. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.