All implanted biomaterials are targets of the host’s immune system. While the host inflammatory response was once considered a detrimental force to be blunted or avoided, in recent years, it has become a powerful force to be leveraged to augment biomaterial–tissue integration and tissue repair. In this review, we will discuss the major immune cells that mediate the inflammatory response to biomaterials, with a focus on how biomaterials can be designed to modulate immune cell behavior to promote biomaterial–tissue integration. In particular, the intentional activation of monocytes and macrophages with controlled timing, and modulation of their interactions with other cell types involved in wound healing, have emerged as key strategies to improve biomaterial efficacy. To this end, careful design of biomaterial structure and controlled release of immunomodulators can be employed to manipulate macrophage phenotype for the maximization of the wound healing response with enhanced tissue integration and repair, as opposed to a typical foreign body response characterized by fibrous encapsulation and implant isolation. We discuss current challenges in the clinical translation of immunomodulatory biomaterials, such as limitations in the use of in vitro studies and animal models to model the human immune response. Finally, we describe future directions and opportunities for understanding and controlling the biomaterial–immune system interface, including the application of new imaging tools, new animal models, the discovery of new cellular targets, and novel techniques for in situ immune cell reprogramming.

中文翻译：

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用于组织修复的免疫调节生物材料

所有植入的生物材料都是宿主免疫系统的目标。虽然宿主炎症反应曾经被认为是一种需要减弱或避免的有害力量，但近年来，它已成为一种强大的力量，可用于增强生物材料-组织整合和组织修复。在这篇综述中，我们将讨论介导对生物材料的炎症反应的主要免疫细胞，重点是如何设计生物材料来调节免疫细胞行为以促进生物材料-组织整合。特别是，以受控时间有意激活单核细胞和巨噬细胞，并调节它们与参与伤口愈合的其他细胞类型的相互作用，已成为提高生物材料功效的关键策略。为此，生物材料结构的精心设计和免疫调节剂的受控释放可用于操纵巨噬细胞表型，以通过增强组织整合和修复来最大化伤口愈合反应，这与以纤维包裹和植入物隔离为特征的典型异物反应相反。我们讨论了免疫调节生物材料临床转化的当前挑战，例如使用体外研究和动物模型来模拟人类免疫反应的局限性。最后，我们描述了理解和控制生物材料-免疫系统界面的未来方向和机会，包括新成像工具的应用、新动物模型、新细胞靶点的发现以及原位免疫细胞重编程的新技术。