Reducing dose requirement of BMP-2 for osseous regeneration by microgeometry-indu

摘要 当患者患有牙周和颅面手术时，经常需要骨再生 牙槽骨严重吸收，上颌底不佳，颅面创伤，或先天性腭裂。 目前的治疗方法依赖于诱导自体骨和同种异体骨来诱导具有临床意义的骨。 而骨传导性骨替代物不能再生。然而，自体移植物受到可用性的限制 第二，发病率和同种异体移植受到较差和不可预测的愈合结果的限制。成骨 骨形态发生蛋白(如BMP-2)是一种有效的骨诱导剂，因此对 牙周和颅面骨再生。然而，传统上BMP仅在以下情况下有效 超生理剂量会导致严重的并发症和较高的手术费用。减少剂量 迫切需要更安全、更具成本效益的临床使用。我们假设一种新的本质上 骨诱导生物材料在作为骨传导材料的同时，可以降低BMP-2的剂量需求 脚手架。我们提出补偿或协同效应可以显著促进骨形成，因为 BMP-2剂量需求会随着本征水平的增加而降低。 骨诱导能力。这样一种结合的方法还没有报道。一种新型微凹面 将为这项研究开发羟基磷灰石半球体(McHas)。为了检验我们的假设，我们建议(1) 开发具有可控微凹大小和降解率的高质量McHa，可导致不同 诱导成骨能力；(2)体外检测McHas的成骨诱导能力；(3)体外评价 McHas对BMP-2体内剂量需求的影响(4)评价McHas对剂量的影响 对BMP-2的要求。该项目的成功将产生一种临床上更安全、更具成本效益的新型 骨移植替代物，可极大地促进牙周和颅面外科的骨再生。 此外，研究活动将大大丰富和加强生物医学研究的倡议，在 我们研究所，通过推动新的研究主题，促进部门、教职员工和 实验室，并在我们的生物医学相关项目中培训学生。

Abstract Periodontal and craniofacial surgeries frequently require bone regeneration when patients suffer from severely resorbed alveolar bone and poor maxillary floor, craniofacial trauma, or congenital cleft palate. Current treatments rely on osteoinductive autografts and allografts to induce clinically significant bone regeneration whereas osteoconductive bone substitutes cannot. However, autografts are limited by availability and second morbidity and allografts are limited by inferior and unpredictable healing outcomes. Osteogenic bone morphogenetic proteins (such as BMP-2) are potent bone inducer therefore they are very attractive for periodontal and craniofacial bone regeneration. However, traditionally BMPs are only effective at supraphysiological doses which can induce significant complications and high surgery cost. Reducing dose requirement is urgently needed for their safer and cost-effective clinical use. We hypothesize a new intrinsically osteoinductive biomaterial can reduce the dose requirement of BMP-2 while serve as an osteoconductive scaffold. We propose a compensating or synergistic effect may significantly promote bone formation because of the combination, and the BMP-2 dose requirement will decrease with the increase of the level of the intrinsic osteoinductive ability. Such a combined approach has not been reported yet. A novel micro-concave hydroxyapatite hemispheres (McHAs) will be developed for the study. To test our hypothesis, we propose to (1) Develop high-quality McHAs with controlled micro-concavity size and degradation rate that can induce varied osteoinductive-like ability; (2) In vitro examine the osteoinductive-like property of McHAs; (3) In vitro evaluate the effect of McHAs on dose requirement of BMP-2 (4) In vivo evaluate the effect of McHAs on dose requirement of BMP-2. The success of the project will generate a new type of clinically safer, cost-effective bone graft substitute that can greatly improve osseous regeneration in periodontal and craniofacial surgeries. In addition, the research activity will significantly enrich and strengthen the biomedical research initiatives at our institute, by prompting new research themes, promoting collaboration among departments, faculty and laboratories, and training students in our biomedical related programs.