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的装置（例如，导管、扩张器、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建。对于所有的生物材料，生物相容性必须不仅包括整合到宿主中的能力，而且还包括功能。巨噬细胞提供与植入物周围的组织协同作用的化学信号，以使其与宿主整合。尽管进行了多年的体外细胞培养研究来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，但并不存在真正的生物相容性理论。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，所涉及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，将需要在体内的理解，在生物材料植入后的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。目标1的重点是创造新的微透析采样策略，在体内测量的异物反应化学。特定的分析物靶标包括细胞因子、类二十烷酸和基质金属蛋白酶。目标2将使用先前与目标1一起创建的方法来测试体内生物制剂释放到植入的生物材料中。最后，目标3将集中在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。公众健康声明。有效装置或工程组织的植入为在许多情况下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，有时需要拆除。通过对与异物反应相关的负责化学信号进行体内测量的更定量的方法，将显著降低再结晶过程的频率。对于需要深入了解并需要控制伤口愈合反应的领域，如整形外科，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.