1 Department of Chemical and Biomolecular Engineering, Vanderbilt University , Nashville, Tennessee.
Tissue Eng Part A. 2014 Jan;20(1-2):115-29. doi: 10.1089/ten.TEA.2012.0762. Epub 2013 Oct 2.
There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling.
临床上迫切需要具有初始类似骨机械性能的骨移植物,这些移植物能够积极重塑,以修复承重骨缺损,如胫骨平台和椎体骨折。然而,目前用于研究承重骨移植物在临床前模型中重塑的研究很少,因此对于这些移植物在体内重塑的机制知之甚少。在这项研究中,我们研究了新骨形成率、基质吸收率和聚合物降解率对可凝固承重聚氨酯/同种异体移植物复合材料在兔股骨髁缺损模型中愈合的影响。研究表明,移植物在体内诱导进行性愈合,新骨形成增加,6 至 12 周时残留同种异体移植物和聚合物减少。然而,自催化聚合物降解率和零级(与时间无关)新骨形成率之间的不匹配导致复合材料内部未完全愈合。用重组人骨形态发生蛋白-2增强移植物不仅增加了新骨形成的速率,而且改变了聚合物的降解机制,使其接近零级过程。随后,新骨形成和聚合物降解速率的匹配导致在移植物的所有区域的后期时间点有更广泛的愈合。这些观察结果强调了平衡新骨形成和降解速率以促进可凝固承重骨移植物愈合的重要性,这些移植物保持类似骨的强度,同时积极重塑。