This one-year BIRT research supplement dramatically expands the impact of our recently-funded 5-year NIH Bioengineering Research Partnership Grant (AR56943-01) by exploring translational applications for tendon and ligament repair based on fundamental research at the interface of tissue engineering and developmental biology (TE/DB). The collaboration is among four faculty in the Department of Biomedical Engineering at the University of Cincinnati (David Butler, PhD, and Jason Shearn, PhD, tissue engineers and Professor and Assistant Professor, respectively;Mary Beth Privitera, M. Design, an industrial designer, Associate Professor and independent investigator;and Scott Wampler, B.S., an entrepreneur and recently-hired Assistant Professor) and Heather Powell, PhD, Assistant Professor of Materials Science and Engineering at the Ohio State University. Working with our TE/DB group, the faculty team will advise three teams of undergraduate and graduate students in industrial design, business, and biomedical engineering to design and implement the commercialization of biological augmentation constructs (BACs) for tendon and ligament autograft repair. These devices will be composed of mesenchymal stem cells (MSCs) seeded in growth factor-infused scaffolds. The core team (two graduate students in biomedical engineering plus two undergraduate cooperative education students in industrial design and business) will spend the first three months developing an innovation brief or problem statement for designing these novel biologics. The team will survey thought leaders in the field and then interview our group of sports medicine knee and shoulder surgeons (consultants on the BRP) and observe surgeries to reconstruct tendons and ligaments in the operating room. These experiences will enable this team to identify design criteria for success and impediments to be overcome in translating tissue engineered augmentations from the laboratory to the patient. In the remaining nine months, the core team will directly supervise two undergraduate BME implementation teams, one in our department's """"""""Research Focused"""""""" track and the other in our """"""""Medical Device Innovation and Entrepreneurship Program"""""""" (MDIEP). The three teams will be charged with developing viable solutions that can be tested both in vitro and in a rabbit tendon autograft model at surgery. The Research team will focus on biological and biomechanical issues in the proposed designs while the MDIEP team will concentrate on human factors challenges (e.g. handling, fixation, and implantation) in delivering soft tissue graft augmentations. The designs will naturally follow from our BRP research, but with a more comprehensive BIRT team spanning from the benchtop to the bedside. The model will be expanded and improved in future R01 applications by the team, serve as a conduit for recruiting talented undergraduate students into our graduate biomedical engineering program at UC, and represent a case study for many other tissue engineering applications.
The proposed research is relevant to public health in that surgeons are seeking ways to enhance the quality and longevity of tendon and ligaments grafts in their patients. Augmentation of these grafts with growth factor-infused constructs seeded with autogolous mesenchymal stem cells could improve the integrity and function of these grafts. Developing an approach for translating these laboratory-generated constructs into clinically useful products could find broad utility in soft tissue reconstructive surgery.
|Arble, Jessica R; Lalley, Andrea L; Dyment, Nathaniel A et al. (2016) The LG/J murine strain exhibits near-normal tendon biomechanical properties following a full-length central patellar tendon defect. Connect Tissue Res 57:496-506|
|Liu, Han; Xu, Jingyue; Liu, Chia-Feng et al. (2015) Whole transcriptome expression profiling of mouse limb tendon development by using RNA-seq. J Orthop Res 33:840-8|
|Lalley, Andrea L; Dyment, Nathaniel A; Kazemi, Namdar et al. (2015) Improved biomechanical and biological outcomes in the MRL/MpJ murine strain following a full-length patellar tendon injury. J Orthop Res 33:1693-703|
|Dyment, Nathaniel A; Breidenbach, Andrew P; Schwartz, Andrea G et al. (2015) Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis. Dev Biol 405:96-107|
|Ratcliffe, Anthony; Butler, David L; Dyment, Nathaniel A et al. (2015) Scaffolds for tendon and ligament repair and regeneration. Ann Biomed Eng 43:819-31|
|Breidenbach, Andrew P; Dyment, Nathaniel A; Lu, Yinhui et al. (2015) Fibrin gels exhibit improved biological, structural, and mechanical properties compared with collagen gels in cell-based tendon tissue-engineered constructs. Tissue Eng Part A 21:438-50|
|Breidenbach, Andrew P; Aschbacher-Smith, Lindsey; Lu, Yinhui et al. (2015) Ablating hedgehog signaling in tenocytes during development impairs biomechanics and matrix organization of the adult murine patellar tendon enthesis. J Orthop Res 33:1142-51|
|Guilak, Farshid; Butler, David L; Goldstein, Steven A et al. (2014) Biomechanics and mechanobiology in functional tissue engineering. J Biomech 47:1933-40|
|Mow, Van C; Butler, David L; Nerem, Robert M (2014) A brief history of USNCB: motivation and formation. J Biomech Eng 136:060301|
|Gilday, Steven D; Casstevens, E Chris; Kenter, Keith et al. (2014) Murine patellar tendon biomechanical properties and regional strain patterns during natural tendon-to-bone healing after acute injury. J Biomech 47:2035-42|
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