SBIR Phase I: Nanostructured Calcium Phosphate Injectable Cements for Treatment of Osteoporosis

这个小型企业创新研究(SBIR)第一阶段项目旨在开发一种可注射的骨科水泥，由含有可交叉连接的官能团的低聚物和增强相的磷酸钙纳米晶制成，可以注入低强度的骨骼中，以提供机械强度和生物活性。与目前的骨水泥不同，该系统将具有出色的操作性能，在注射部位保持局部，并在体温下快速硬化，无需化学引发剂，产生的热量最少。这项研究将通过检测固化时间、固化温度、反应热、流变性、化学结构、强度和体外生物活性等性能来研究这些新型低聚物体系的化学组成以及磷酸钙纳米晶形态、表面化学和负载的影响。在商业上，该应用提供了一种替代目前使用的手术粘固剂(甲基丙烯酸甲酯的原位聚合)，用于全关节置换。虽然目前的方法已经安全地使用，但随着手术的需要扩展到更敏感的组织，如脊柱，以及新的程序被开发，许多安全和疗效问题需要解决。每年约有70万例脊椎骨折发生；保守治疗无效的患者有可能接受微创手术，在标签外使用现有的骨水泥治疗椎体压缩骨折。然而，低粘度骨水泥的液体渗漏会导致软组织损伤以及神经根疼痛和压迫。其他已报道的并发症通常与在脊柱中使用骨水泥有关，包括肺栓塞、呼吸和心力衰竭、腹部侵犯/肠梗阻和死亡。拟议的项目将缓解其中许多问题，并为治疗骨质疏松症开辟新的方法和机制。

This Small Business Innovative Research (SBIR) Phase I project aims to develop an injectable orthopedic cement made from oligomers containing cross-linkable functional groups and a reinforcing phase of calcium phosphate nanocrystals that can be injected into low strength bone to provide mechanical strength and bioactivity. This system will have excellent handling properties, remain localized at the injection site, and rapidly harden at body temperature without chemical initiators and with a minimal heat generation, unlike current bone cements. The research will investigate the chemistry of these novel oligomer systems and the effect of calcium phosphate nanocrystal morphology, surface chemistry, and loading by examining properties such as cure time, cure temperature, heat of reaction, rheological behavior, chemical structure, strength and in vitro bioactivity. Commercially, the application provides an alternative surgical cement to what is in current use (in situ polymerization of methylmethacrylate) for total joint replacement. While current methods have been used safely, as the need for a surgical has spread to more sensitive tissues, such as the spine, and new procedures are developed, numerous safety and efficacy issues need to be addressed. About 700,000 vertebral fractures occur annually; patients not responsive to conservative treatment are potential candidates for minimally invasive procedures that use current bone cements off-label to treat vertebral compression fractures. However, leakage of liquid from low viscosity bone cements can result in soft tissue damage as well as nerve root pain and compression. Other reported complications, generally associated with the use of bone cements in the spine, include pulmonary embolism, respiratory and cardiac failure, abdominal intrusions/ileus, and death. The proposed project will alleviate many of these issues and open new methods and mechanisms for the treatment of osteoporosis.