Whitlockite nanoparticles for inducing bone regeneration

项目摘要/摘要 骨不连骨折是一种永久性骨折，不会自行愈合，可发生在任何骨骼中。 组织，造成患者剧烈疼痛和身体残疾。然而，到目前为止，还没有有效的 骨不连的治疗及其病理机制尚不清楚。治疗骨不连 骨折、骨移植材料通常被植入受损区域以刺激骨再生和 来支撑骨骼结构。在各种骨植入材料中，羟基磷灰石(HAP：Ca10(PO4)6(OH)2)和 β-磷酸三钙(β-TcP：Ca3(PO4)2)以其优异的性能成为目前应用最广泛的生物材料 生物相容性和生物可再吸收性。然而，β-tcp并不存在于我们的骨骼中，而它已经 微米级颗粒。在这方面，目前的骨植入材料，由羟基磷灰石和β-tcp组成，并不 在纳米尺度上反映骨的成分和结构，因此与天然骨组织存在差距，即 最终被新骨取代。因此，要在植骨材料上取得突破， 我们计划重新创造一种创新的骨植入材料，它可以立即与 植入后的周围骨组织，通过利用两种主要的骨矿--白锁石(WH： Ca18Mg2(HPO4)2(PO4)12)和HAP。WH是骨骼中第二丰富的晶体，也是已知存在的 在低龄和骨组织形成早期比例较高。然而，尽管它意义重大 WH在骨骼中的分布，由于其合成和合成的困难，在很大程度上被研究领域忽视了。 分析。最近，报道了一种简便的wh纳米颗粒的合成方法，其有益的 对细胞增殖和活性的影响已经被证明。在这项研究中，我们的目标是重建 仿骨种植平台通过控制和优化两大部分的组成和结构 3D水凝胶平台中的骨矿物质。我们假设两相WH/HAP复合材料将提供 材料、机械和生物特性对细胞增殖和分化的协同效应。 这一假设将通过以下具体目标得到验证：1)评估MSCs向 含有不同比例的羟基磷灰石和羟基磷灰石纳米颗粒的纳米复合凝胶中的成骨细胞；2)对照 用3D打印技术构建MSC负载的WH/HAP纳米复合凝胶的空间结构；3)评估骨骼 WH/HAP纳米复合凝胶在体内的形成能力。我们预计，拟议中的 研究将提供对骨组织的更好理解和对骨不连骨折的有效治疗。

Project Summary/Abstract Nonunion fracture is a permanently broken bone that does not spontaneously heal and can occur in any bone tissue, causing severe pain and physical disability to patient. However, until now, there is no effective treatment for nonunion fracture and its pathological mechanism remains unidentified. To treat nonunion fracture, bone graft materials are often implanted into the damaged region to stimulate bone regeneration and to support bone structure. Among various bone implant materials, hydroxyapatite (HAP: Ca10(PO4)6(OH)2) and β-tricalcium phosphate (β-TCP: Ca3(PO4)2) are the most widely used biomaterials due to excellent biocompatibility and bioresorbability, respectively. However, β-TCP does not exist in our bone while it has microscale particle. In this respect, the current bone implant material, composed of HAP and β-TCP, does not reflect composition and structure of bone at nanoscale and thus has a gap with natural bone tissue, that it is eventually purposed to be replaced by new bone. Therefore, to make a breakthrough in bone implant material, we propose to recreate an innovative bone implant material which can immediately harmonize with surrounding bone tissue after implantation, by utilizing the two major bone minerals, whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) and HAP. WH is the second most abundant crystal in bone and also known to exist with high ratio in younger aged and early stage of bone tissue formation. However, despite its significant distributions in bone, WH has been largely ignored from the research fields due to difficulty in its synthesis and analyses. Very recently, a facile synthetic method of WH nanoparticles has been reported and its beneficial effects on cellular proliferation and activities has been demonstrated. In this research, we aim to recreate bone-mimetic implant platform by controlling and optimizing the composition and the structure of the two major bone minerals in 3D hydrogel platform. We hypothesized that the two-phase WH/HAP composite will provide synergetic effects of material-, mechanical-, and biological properties on cellular proliferation and differentiation. This hypothesis will be verified by the following specific aims: 1) Assess the differentiation of MSCs into osteogenic cells in nanocomposite gels containing various ratios of WH and HAP nanoparticles; 2) Control the spatial architecture of MSC-laden WH/HAP nanocomposite gels by 3D printing; and 3) Assess the bone formation ability of WH/HAP nanocomposite gels in vivo. We expect that the new findings from the proposed research will provide better understandings of bone tissue and effective treatment for nonunion fractures.