Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

Abstract

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.

Effects of Surface-Bound Collagen-Mimetic Peptides on Macrophage Uptake and Immunomodulation

“…PLGA MP uptake is relevant to drug delivery as PLGA has been used as vehicles for hydrophobic drug payloads (Abdelaziz et al, 2018;Liu et al, 2018). In the context of implant integration, PLGA MPs can be a model for debris from PLGA-based medical devices/implants (Yoshida and Babensee, 2006;Yang et al, 2009), which are often plagued with inflammation (Kim and Park, 2006;Jiao and Cui, 2007;Brandhonneur et al, 2009;Sun et al, 2017;Rowley et al, 2019). Our PLGA uptake data suggests the potential of integrating LAIR1-LP into materials as a possible strategy to improve biomaterials for drug delivery and medical devices/implants.…”

“…Specific regions of collagen are recognized as ligands by different receptors expressed by immune cells; these receptors include integrins, discoidin domain receptors, immunoglobulin-like receptors, and mannose receptors, resulting in diverse immunomodulatory responses (Leitinger, 2011). Interaction with natural collagen matrices, reconstituted collagen hydrogels, and/or collagen peptides has been shown to increase cellular adhesion and integrin expression in both adaptive and innate immune cells, as well as actively modulate the phenotype of immune cells in a variety of ways, affecting a range of immune cell functions (Reyes and García, 2004;Zaveri et al, 2014;Boraschi-Diaz et al, 2017;Rowley et al, 2019). More specifically, adhesion to collagen generally reduces the inflammatory response of macrophages, and is thought to have a critical regulatory role in setting the threshold for innate immune responses in tissue (Meyaard, 2010).…”

Utility of Air Bladder-Derived Nanostructured ECM for Tissue Regeneration

“…Indeed, as demonstrated in previous studies the ECM contains not only collagenous protein but also preserve significant amount of growth factors, proteoglycan, etc. (Badylak, 2007;Rowley et al, 2019). These components in ECM might play an important role during MC3T3-E1 osteogenic differentiation.…”

Optimization of a Decellularization/Recellularization Strategy for Transplantable Bioengineered Liver

“…As the technology of biomaterials developed, the definition expanded to include substances to control the biological environment of cells and tissues for increased compatibility with a host to allow for colonization, proliferation, and differentiation of cells while maintaining their specific morphologies, configurations and avoiding immunological rejection. Based on the increasing knowledge of ECM biology, scaffold biomaterials can be grouped as synthetic materials, natural materials, or a decellularized matrix [12]. Moreover, modifications have been made to enhance the biologically active signals of scaffolds, leading to improved cell attachment, survival, and tissue formation [13,14].…”