Injectable weight-bearing bone grafts for healing of tibial plateau fractures

用于愈合胫骨平台骨折的可注射承重骨移植物

基本信息

批准号：
8652439
负责人：
Scott A Guelcher
金额：
$ 21.02万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-15 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8652439
关键词：
Affect Biomechanics Bone Transplantation Cells Clinical Compressive Strength Defect Depressed mood Distal Equilibrium Exhibits Failure Fatigue Femur Fracture Glass Healed Histology Injectable Injection of therapeutic agent Injury Instruction Joints Measures Mechanics Modeling Morbidity - disease rate Orthopedic Procedures Oryctolagus cuniculus Osteogenesis Outcome Pathway interactions Patients Performance Polymers Polyurethanes Pre-Clinical Model Process Property Radial Recovery Research Risk Shear Strength Sheep Structure Testing Transplanted tissue Weight-Bearing state allogenic bone transplantation bone calcium phosphate clinical practice graft healing healing improved in vivo morphometry particle pre-clinical prevent public health relevance reconstruction sample fixation standard of care substantia spongiosa tibia tricalcium phosphate

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：胫骨高原骨折涉及重量关节，并且通常具有抑郁症的部分，需要大量开放式减少和内固定方法，以及软骨下嫁接以维持关节的一致性。可注射的磷酸钙水泥（CPC）是当前的护理标准，但它们既不允许早起，也不保护无法或将无法遵守有限的重量轴承说明的患者。因此，约有25％的严重胫骨高原骨折失败，需要重新寄养，这导致预后不良的风险增加。这些临床观察结果强调了对可注射，可固定和重量的移植物的临床需求，这将防止固定性的灾难性失败以及随后严重的胫骨高原骨折的发病率。 CPCS的有希望的替代方法是可注射的，可固定的复合材料，该复合材料包含颗粒基质成分（同种异体移植骨，生物活性玻璃或磷酸三中钙），该复合材料嵌入了两种可分离的聚氨酯（PUR）Binder中。通过简单混合3个组件，然后将其注入缺陷来制备移植物。在接近随机关闭包装（RCP）极限（64 vol％）的体积分数时，颗粒矩阵分量为细胞提供了几乎连续的取代途径，可通过蠕变替代过程积极浸润和重塑移植物。 PUR复合移植物具有与小梁骨相媲美的机械性能，超过了CPC的机械性能，并且在兔远端股骨缺陷中也经历了平衡的重塑，从而表明在愈合过程中保留了骨样机械性能。在此提案中，我们将研究移植物组成的影响，包括基质组成，基质载荷和PUR降解以及机械载荷对体内的重塑。我们还将在绵羊中同时利用非重量和重量的缺陷，以确定PUR复合移植物在重塑时是否保持骨状机械性能。最后，我们将评估机械挑战性的卵子胫骨平原插槽缺陷中的PUR复合移植物，以确定在严格的临床前模型中，PUR/基质移植物在功能上是否具有功能性负重，其中临床护理标准（CPC）失败。