Whitlockite nanoparticles for inducing bone regeneration

项目总结/摘要 骨不连骨折是一种永久性骨折，不能自发愈合，可发生在任何骨 组织，导致患者严重疼痛和身体残疾。然而，到目前为止，还没有有效的 骨不连的治疗方法及其病理机制尚不清楚。治疗骨不连 骨折时，通常将骨移植材料植入受损区域以刺激骨再生， 来支撑骨骼结构在各种骨植入材料中，羟基磷灰石（HAP：Ca 10（PO 4）6（OH）2）和 β-磷酸三钙（β-TCP：Ca 3（PO 4）2）是目前应用最广泛的生物材料， 生物相容性和生物可吸收性。然而，β-TCP并不存在于我们的骨骼中， 微尺度粒子在这方面，由HAP和β-TCP组成的当前骨植入材料不 在纳米级上反映骨的组成和结构，因此与天然骨组织有差距， 最终被新骨取代。因此，为了在骨植入材料方面取得突破， 我们建议重新创造一种创新的骨植入材料， 植入后周围骨组织，通过利用两种主要的骨矿物质，白洛克石（WH： Ca 18 Mg 2（HPO 4）2（PO 4）12）和HAP。WH是骨骼中含量第二高的晶体， 在年轻人和骨组织形成早期的比例较高。然而，尽管其重要性 由于WH在骨中的分布，由于其合成困难， 分析。最近，已经报道了一种简易的WH纳米颗粒的合成方法，其有益效果是： 对细胞增殖和活性的影响。在这项研究中，我们的目标是重建 通过控制和优化两种主要成分的组成和结构， 骨矿物质在3D水凝胶平台。我们假设两相WH/HAP复合材料将提供 材料、机械和生物学特性对细胞增殖和分化的协同作用。 这一假设将通过以下具体目的来验证：1）评估MSC分化为 在含有各种比例的WH和HAP纳米颗粒的纳米复合凝胶中的成骨细胞; 2）控制 通过3D打印的MSC负载的WH/HAP纳米复合凝胶的空间结构;以及3）评估骨 WH/HAP纳米复合凝胶在体内的形成能力。我们预计，新的发现，从拟议的 研究将提供对骨组织更好的了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.