Quantitative Biocompatibility of Implanted Materials

描述(申请人提供)：临床意义。生物材料被广泛用于植入的设备(如导管、除颤器、支架和传感器)，并被考虑用于组织工程应用，以提供疾病或损伤后的组织重建。对于所有生物材料来说，生物相容性不仅必须包括融入宿主的能力，而且还必须具有功能。巨噬细胞提供化学信号，与植入物周围的组织协同作用，使植入物与宿主整合。尽管多年来进行了体外细胞培养研究以评估巨噬细胞对材料的反应，并进行了体内组织病理学实验，但真正的生物相容性理论尚不存在。由于缺乏能够解决这一复杂的化学分析问题的生物分析工具，对所涉及的体内信号分子的绝对确认仍然难以捉摸。要实现组织生物工程的快速发展，需要在体内了解生物材料植入后不同时间阶段所涉及的信号化学物质。实验方法。拟议的工作有三个具体目标。目的1专注于创造新的微透析取样策略，用于体内异物反应化学的测量。特定的分析目标包括细胞因子、二十烷基类化合物和基质金属蛋白酶。AIM 2将使用之前与AIM 1共同创建的方法来测试植入生物材料的体内生物剂释放。最后，目标3将侧重于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。发表公共卫生声明。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，这些设备通常与主机不兼容，有时需要移除。通过一种更定量的方法在体内测量与异物反应相关的负责任的化学信号，移植过程的频率将显著减少。对于需要深入了解并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.