Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA.
Department of Biomedical Engineering, University of California, Irvine, CA, 92697, USA.
Adv Healthc Mater. 2019 Apr;8(8):e1801578. doi: 10.1002/adhm.201801578. Epub 2019 Feb 4.
The extracellular matrix (ECM) is a complex and dynamic structural scaffold for cells within tissues and plays an important role in regulating cell function. Recently it has become appreciated that the ECM contains bioactive motifs that can directly modulate immune responses. This review describes strategies for engineering immunomodulatory biomaterials that utilize natural ECM-derived molecules and have the potential to harness the immune system for applications ranging from tissue regeneration to drug delivery. A top-down approach utilizes full-length ECM proteins, including collagen, fibrin, or hyaluronic acid-based materials, as well as matrices derived from decellularized tissue. These materials have the benefit of maintaining natural conformation and structure but are often heterogeneous and encumber precise control. By contrast, a bottom-up approach leverages immunomodulatory domains, such as Arg-Gly-Asp (RGD), matrix metalloproteinase (MMP)-sensitive peptides, or leukocyte-associated immunoglobulin-like receptor-1(LAIR-1) ligands, by incorporating them into synthetic materials. These materials have tunable control over immune cell functions and allow for combinatorial approaches. However, the synthetic approach lacks the full natural context of the original ECM protein. These two approaches provide a broad range of engineering techniques for immunomodulation through material interactions and hold the potential for the development of future therapeutic applications.
细胞外基质（ECM）是组织内细胞的复杂而动态的结构支架，在调节细胞功能方面发挥着重要作用。最近人们认识到，ECM 中含有生物活性基序，可直接调节免疫反应。本综述描述了用于工程化免疫调节生物材料的策略，这些策略利用天然 ECM 衍生分子，并有可能利用免疫系统将其应用于从组织再生到药物输送等多个领域。自上而下的方法利用全长 ECM 蛋白，包括胶原蛋白、纤维蛋白或基于透明质酸的材料，以及源自脱细胞组织的基质。这些材料具有保持天然构象和结构的优点，但往往是异质的，难以精确控制。相比之下，自下而上的方法通过将 Arg-Gly-Asp（RGD）、基质金属蛋白酶（MMP）敏感肽或白细胞相关免疫球蛋白样受体-1（LAIR-1）配体等免疫调节结构域整合到合成材料中，利用它们来发挥作用。这些材料可对免疫细胞功能进行可调控制，并允许采用组合方法。然而，这种合成方法缺乏原始 ECM 蛋白的完整天然背景。这两种方法为通过材料相互作用进行免疫调节提供了广泛的工程技术，并有可能开发出未来的治疗应用。
