Collaborative Research: Regulators of cellular microenvironment and multiscale osteointegration

ID：MPS/dmr/bmat(7623)1106165 PI：Wager Johnson，Amy 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：协作研究：细胞微环境调节器和多尺度骨整合电子优点：磷酸钙(CAP)被广泛应用于包括种植体涂层和骨再生/修复在内的广泛应用中，因为它们的许多属性使其成为与骨骼接触的理想材料。然而，调控帽的骨整合的机制尚不清楚。由于缺乏适当的工具和方法来隔离关键监管机构以及以受控和系统的方式将它们结合起来，进展停滞不前。有三个因素对CAP系统特别重要：微孔率、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在存在微孔的情况下隔离BMP-2和促进生物磷灰石的形成。我们的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的相互作用，并利用CAPS作为生物材料平台和一套独特的工具，了解它们影响背后的机制。大孔(100um)和微孔(50um)的盖子与只有大孔的盖子相比，极大地促进了骨整合。虽然微孔主要用于促进大孔的生长，但现在有证据表明，微孔也是骨的空间，它包含在帽状支架中可以导致大孔和微孔中的多尺度骨整合(MSO)-骨生长。这是任何其他系统都没有实现的。这套独特的工具将用于研究关键调节剂、微孔率、BMP-2和生物磷灰石的作用，以及它们影响骨整合的机制。这些工具允许(1)控制微孔率，这使得能够系统地探索微孔率和相关特征，(2)将BMP-2以不同程度的亲和力附着在帽上，这为研究隔离和释放BMP-2的效果提供了独特的机会，以及(3)能够在帽的表面生长生物磷灰石，从而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控制。具体的目标是：(1)确定细胞迁移的最小孔径，给出一种有效的趋化和骨诱导刺激，BMP-2。这对于建立MSO的孔隙特征界限是至关重要的。(2)确定刺激物对骨髓间充质干细胞向基质诱导的影响。(3)确定刺激在基质生成和矿化中的影响。BROADER影响：综合考虑，本文所使用的系统方法将所描述的因素与拟议的分析相结合，将为与骨接触的生物材料的合理设计提供新的见解。这些潜在的进展将导致对骨/材料相互作用的新理解，可能对那些受到骨丢失或关节故障(如涂层植入物)影响的人有巨大的好处，并可能减轻与这些手术相关的一些经济负担。主要的教育活动与开发一个教学模块有关，该模块采用以探究为基础的方法，并让伊利诺伊州厄巴纳的校园女子中学(CMSG)的科学教师参与研究活动。与CMSG合作的目标是积极影响女孩？对STEM的看法，这可能会导致他们在实地坚持下去。与CMSG的合作是与现有的NSF NSEC合作进行的，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.