Department of Chemical and Biological Engineering, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
J Orthop Res. 2013 Mar;31(3):401-6. doi: 10.1002/jor.22243. Epub 2012 Oct 15.
Medtronic's INFUSE Bone Graft provides surgeons with a potent tool for stimulating bone formation. Current delivery vehicles that rely on Absorbable Collagen Sponges (ACS) require excessive quantities of the active ingredient in INFUSE, recombinant human Bone Morphogenic Protein-2 (rhBMP2), to achieve physiologically relevant concentrations of the growth factor, driving up the cost of the product and increasing the likelihood of undesirable side effects in neighboring tissues. We demonstrate that a simple light-mediated, thiol-ene chemistry can be used to create an effective polymer delivery vehicle for rhBMP2, eliminating the use of xenographic materials and reducing the dose of rhBMP2 required to achieve therapeutic effects. Comprised entirely of synthetic components, this system entraps rhBMP2 within a biocompatible hydrogel scaffold that is degraded by naturally occurring remodeling enzymes, clearing the way for new tissue formation. When tested side-by-side with ACS in a critical-sized bone defect model in rats, this polymeric delivery system significantly increased bone formation over ACS controls.
美敦力的 INFUSE 骨移植物为外科医生提供了一种刺激骨形成的有效工具。目前依赖可吸收胶原海绵(ACS)的输送载体需要过量的 INFUSE 中的活性成分,即重组人骨形态发生蛋白-2(rhBMP2),以达到生长因子的生理相关浓度,从而增加产品成本,并增加邻近组织产生不良副作用的可能性。我们证明,简单的光介导的硫醇-烯化学可以用于创建 rhBMP2 的有效聚合物输送载体,从而消除了异种材料的使用,并减少了达到治疗效果所需的 rhBMP2 剂量。该系统完全由合成成分组成,将 rhBMP2 困在生物相容性水凝胶支架内,该支架可被天然存在的重塑酶降解,为新组织形成扫清道路。在大鼠的临界尺寸骨缺损模型中与 ACS 进行并排测试时,这种聚合物输送系统显著增加了 ACS 对照的骨形成。