Tibial plateau fractures involve a weight-bearing joint and often have depressed portions that require extensive open reduction and internal fixation approaches along with subchondral grafting to maintain articular congruence. Injectable calcium phosphate cements (CPCs) are the current standard of care, but they neither allow early weight-bearing nor do they protect the patient who cannot or will not comply with the limited weight- bearing instructions. Consequently, ~25% of severe tibial plateau fractures fail, requiring rehospitalization which results in an increased risk of a poor outcome. These clinical observations underscore the clinical need for an injectable, settable, and weight-bearing graft that will prevent catastrophic failure of the fixation and subsequent morbidity of severe tibial plateau fractures. A promising alternative to CPCs is injectable, settable composites comprising a particulated matrix component (allograft bone, bioactive glass, or tricalcium phosphate) embedded in a two-component resorbable polyurethane (PUR) binder. The grafts are prepared by simple mixing of 3 components followed by injection into the defect. At volume fractions approaching the random close-packing (RCP) limit (64 vol%), the particulated matrix component presents a nearly continuous osteoconductive pathway for cells to actively infiltrate and remodel the graft via the process of creeping substitution. PUR composite grafts exhibit mechanical properties comparable to those of trabecular bone and exceeding those of CPCs, and also undergo balanced remodeling in rabbit distal femur defects, thereby suggesting that bone-like mechanical properties are preserved during the healing process. In this proposal, we will investigate the effects of graft composition, including matrix composition, matrix loading, and PUR degradation, and mechanical loading on remodeling in vivo. We will also utilize both non-weight-bearing and weight-bearing defects in sheep to determine whether PUR composite grafts maintain bone-like mechanical properties as they remodel. Finally, we will evaluate PUR composite grafts in mechanically challenging ovine tibial plateau slot defects to determine whether PUR/matrix grafts are functionally weight-bearing in a stringent preclinical model in which the clinical standard of care (CPC) fails.

Public Health Relevance

Fractures of the joint often have depressed regions that require extensive open reduction and internal fixation approaches along with subchondral grafting to maintain articular congruence. In the proposed research, we will investigate the effects of graft composition and mechanical loading on biomechanical properties and healing in preclinical models. An injectable, settable, and weight-bearing bone graft that possesses suitable mechanical strength and toughness while actively remodeling to form new bone would change clinical practice and likely improve outcomes of acetabular tibial plateau fractures, as well as a number of other orthopaedic procedures, such as vertebroplasty, fractures of the distal radius, and screw augmentation.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Musculoskeletal Tissue Engineering Study Section (MTE)
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Panagis, James S
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Vanderbilt University Medical Center
Engineering (All Types)
Schools of Engineering
United States
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Lu, Sichang; McGough, Madison A P; Shiels, Stefanie M et al. (2018) Settable polymer/ceramic composite bone grafts stabilize weight-bearing tibial plateau slot defects and integrate with host bone in an ovine model. Biomaterials 179:29-45
McEnery, Madison A P; Lu, Sichang; Gupta, Mukesh K et al. (2016) Oxidatively Degradable Poly(thioketal urethane)/Ceramic Composite Bone Cements with Bone-Like Strength. RSC Adv 6:109414-109424
Harmata, Andrew J; Uppuganti, Sasidhar; Granke, Mathilde et al. (2015) Compressive fatigue and fracture toughness behavior of injectable, settable bone cements. J Mech Behav Biomed Mater 51:345-55
Harmata, Andrew J; Ward, Catherine L; Zienkiewicz, Katarzyna J et al. (2014) Investigating the Effects of Surface-Initiated Polymerization of ?-Caprolactone to Bioactive Glass Particles on the Mechanical Properties of Settable Polymer/Ceramic Composites. J Mater Res 29:2398-2407