Collaborative Research: Regulators of cellular microenvironment and multiscale osteointegration

ID：MPS/DMR/BMAT（7623）1106165 PI：瓦戈纳约翰逊，艾米 ORG：伊利诺伊大学ID：MPS/DMR/BMAT（7623）1105591 PI：Murphy，William ORG：威斯康星大学标题：合作研究：细胞微环境和多尺度骨整合的调节剂智力优势：磷酸钙（CaP）用于广泛的应用，包括植入物涂层和骨再生/修复，因为它们的许多属性使其成为与骨接触的理想选择。 然而，CaPs的骨整合调控机制尚不清楚。 由于缺乏适当的工具和方法，无法将关键的监管机构孤立起来，也无法以有控制和有系统的方式将它们联合收割机结合起来，因此进展停滞不前。 三个因素对于CaP系统特别重要：微孔性、BMP-2和生物磷灰石。 与骨整合相关的潜在主导机制被假设为BMP-2的隔离和在微孔存在下生物磷灰石的增强形成。 目标是量化这些因素在骨形成不同阶段的相对重要性和潜在相互作用，并了解其影响背后的机制，使用CaP作为生物材料平台和一套独特的工具。 与仅具有大孔隙的那些相比，具有大孔隙（100 μ m）和微孔（50 μ m）的CaP具有大大增强的骨整合。 虽然微孔性主要用于促进生长到大孔中，但现在有证据表明微孔性也是骨的空间，并且其在CaP支架中的包含物可导致多尺度骨整合（MSO）-骨生长贯穿大孔和微孔。 这是任何其他系统都无法实现的。 这套独特的工具将用于研究关键调控因子、微孔、BMP-2和生物磷灰石的作用，以及它们对骨整合影响的机制。 所述工具允许（1）控制微孔性，其独特地使得能够系统地探索微孔性和相关特征，（2）以不同水平的亲和力将BMP-2连接到CaP，其提供了研究螯合和释放BMP-2两者的作用的独特机会，和（3）在CaP表面上生长生物磷灰石的能力，这使得能够研究生物磷灰石对细胞反应的影响。 此外，这些参数中的每一个都可以独立地控制。 具体目标是：（1）确定在给予有效的趋化性和骨诱导性刺激物BMP-2的情况下细胞将通过其迁移的最小孔径。 这对于确定MSO孔隙特征的界限至关重要。 (2)确定刺激物在将间充质干细胞吸引到基质中的影响。 (3)确定刺激对基质生成和矿化的影响。更广泛的影响：总之，这里使用的系统方法结合联合收割机所描述的因素和拟议的分析将提供新的见解，合理设计的生物材料与骨界面。 这些潜在的进展将导致对骨/材料相互作用的新理解，可能对受骨丢失或关节失效影响的患者（例如涂层植入物）产生巨大的益处，并可能减轻与这些手术相关的一些经济负担。 主要的教育活动涉及开发一个教学模块，该模块采用基于探究的方法，并让校园中学的理科教师参与研究活动。 与CMSG合作的目标是积极影响女孩？对STEM的看法，这可能导致他们在该领域的持久性。 与CMSG的合作是与现有的NSF NSEC合作，学习模块将成为NSF中心现有教育计划的一部分，用于针对代表性不足的群体的计划。

ID: MPS/DMR/BMAT(7623) 1106165 PI: Wagoner Johnson, Amy ORG: University of IllinoisID: MPS/DMR/BMAT(7623) 1105591 PI: Murphy, William ORG: University of WisconsinTitle: Collaborative Research: Regulators of cellular microenvironment and multiscale osteointegrationINTELLECTUAL MERIT: Calcium Phosphates (CaP) are utilized in a wide range of applications including implant coatings and in bone regeneration/repair because of their many attributes that make them ideal to interface with bone. However, the mechanisms regulating osteointegration of CaPs have yet to be understood. Progress has stalled because of a lack of appropriate tools and methodologies that can isolate key regulators as well as combine them in a controlled and systematic way. Three factors stand out as particularly important for the CaP system: microporosity, BMP-2, and biologic apatite. The potential dominating mechanisms relating to osteointegration are hypothesized to be sequestration of BMP-2 and enhanced formation of biologic apatite in the presence of micropores. The goal is to quantify the relative importance of and potential interactions between these factors at different stages of bone formation and to understand the mechanisms behind their influence, using CaPs as a biomaterial platform and a unique set of tools. CaPs with macro (100um) and microporosity (50um) have greatly enhanced osteointegration as compared to those with only macroporosity. While microporosity has been used primarily to enhance growth into macropores, there is now evidence that microporosity is also a space for bone and its inclusion in CaP scaffolds can result in multiscale ostointegration (MSO)-bone growth throughout both macro and micropores. This has not been achieved with any other system. The unique suite of tools will be used to examine the role of key regulators, microporosity, BMP-2, and bioapatite, and the mechanisms behind their influence on osteointegration. The tools allow for (1) control of microporosity, which uniquely enables systematic exploration of microporosity and related characteristics, (2) attaching BMP-2 to CaPs with varying levels of affinity, which provides the unique opportunity to study the effects of both sequestered and releasing BMP-2, and (3) the capability to grow biological apatite on the surface of CaPs, which enables investigation of the influence of biological apatite on cell response. Further, each of these parameters can be independently controlled. The specific objectives are: (1) Determine the minimum pore size through which cells will migrate given a potent chemotactic and osteoinductive stimulus, BMP-2. This is critical for establishing bounds on pore characteristics for MSO. (2) Determine the influence of the stimuli in attracting mesenchymal stem cells to the substrate. (3) Determine the influence of the stimuli in matrix production and mineralization.BROADER IMPACTS: Taken together, the systematic approach used here to combine the factors described and the proposed analysis will provide new insight into the rational design of biomaterials that interface with bone. The potential advances will lead to new understanding of bone/material interactions, could have huge benefit for those affected by bone loss or joint failure (e.g. coated implants), and could relieve some of the economic burden associated with these procedures. The main educational activities are related to developing an instructional module that uses an inquiry-based approach and engages science teachers at the Campus Middle School for Girls (CMSG, Urbana, IL) in research activities. The objective in working with CMSG is to positively influence girls? perceptions of STEM, which may lead to their persistence in the field. The work with CMSG is in partnership with an existing NSF NSEC, and the learning module will become part of the existing educational programs in the NSF Center for use in programs that target underrepresented groups.