Quantitative Biocompatibility of Implanted Materials

描述（由申请人提供）：临床意义。生物材料广泛用于植入设备（例如，导管、除颤器、支架和传感器），并且正在考虑用于组织工程应用，以在疾病或损伤后提供组织重组。对于所有的生物材料，生物相容性不仅包括与宿主结合的能力，还包括其功能。巨噬细胞提供化学信号，与植入物周围的组织协同作用，使其与宿主结合。尽管有多年的体外细胞培养研究来评估巨噬细胞对材料的反应和体内组织病理学实验，但真正的生物相容性理论并不存在。由于缺乏能够解决这一复杂化学分析问题的生物分析工具，对参与的体内信号分子的绝对确认仍然难以捉摸。实现组织生物工程的快速发展需要对生物材料植入后不同时间阶段所涉及的信号化学物质的体内理解。实验方法。拟议的工作有三个具体目标。目的1侧重于创建新的微透析取样策略，用于体内测量异物反应化学。特定的分析目标包括细胞因子，类二十烷和基质金属蛋白酶。Aim 2将使用先前与Aim 1一起创建的方法来测试体内生物制剂对植入生物材料的释放。最后，Aim 3将重点了解不同的预防方法，如细胞因子、药物或生长因子释放如何影响潜在的巨噬细胞信号化学。公共卫生声明。在许多情况下，植入有效的装置或工程组织为改善生活质量提供了希望。但是，这些设备往往与主机不兼容，有时需要移除。如果采用更定量的方法在体内测量与异物反应相关的化学信号，那么移植过程的频率将大大降低。对于需要深入了解和需要控制伤口愈合反应的领域，如整形手术，可能会产生额外的好处。

DESCRIPTION (provided by applicant): Clinical Significance. Biomaterials are widely used for devices that are implanted (e.g., catheters, defibrillators, stents, and sensors) and are being considered for tissue engineering applications to provide tissue restructuring after disease or injury. For all biomaterials, biocompatibility must involve not only an ability to integrate into the host, but also to function. Macrophage cells provide the chemical cues that act in synergy with the tissue that surrounds the implant to integrate it with the host. Despite many years of in vitro cell culture studies to assess the macrophage response to materials and in vivo histopathological experiments, a true theory of biocompatibility does not exist. Absolute confirmation of the in vivo signaling molecules involved has remained elusive due to lack of bioanalytical tools capable of addressing this complex chemical analysis problem. Achieving rapid progress in tissue bioengineering will require an in vivo understanding of the signaling chemicals involved at different temporal stages after biomaterial implantation. Experimental Approach. The proposed work has three specific aims. Aim 1 focuses on creating novel microdialysis sampling strategies for in vivo measurements of the foreign body response chemistry. Particular analyte targets include cytokines, eicosanoids, and matrix metalloproteinases. Aim 2 will use methods previously created in conjunction with Aim 1 to test the in vivo bioagent agent release to implanted biomaterials. Finally, Aim 3 will focus on understanding how different prophylactic approaches such as cytokine, drug, or growth factor release affects the underlying macrophage cellular signaling chemistry. Lay Public Health Statement. Implantation of effective devices or engineered tissue provides promise for improvement of quality of life under many circumstances. However, these devices often have incompatibility with the host and sometimes need to be removed. The frequency of the explantation process would be significantly reduced by a more quantitative approach to in vivo measurement of the responsible chemical signals associated with the foreign body response. Additional benefits may arise for the fields that require an intimate understanding and need to control a wound healing response such as plastic surgery.