The Scaffold Immune Microenvironment: Biomaterial-Mediated Immune Polarization in Traumatic and Nontraumatic Applications<sup />

Hall, Matthew D.; Allen, Brian W.; Estrellas, Kenneth; Housseau, Franck; Pardoll, Drew M.; Elisseeff, Jennifer H.

doi:10.1089/ten.tea.2016.0304

Cited by 72 publications

(60 citation statements)

References 52 publications

(64 reference statements)

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“…However, probing the role of other immune cells in both the innate and adaptive compartments is needed to truly understand the effects of these biomaterials on the immune system. Studies describing the effects of ECM‐based materials on T and B cells have been particularly sparse, as is work on neutrophils and the interface between the innate and adaptive immune systems via DCs and macrophages . Some investigators have moved beyond studying the response of individual immune cell types, developing co‐culture models to analyze cell–matrix–cell crosstalk and more closely mimic the physiologic response to ECM .…”

Section: Discussionmentioning

confidence: 99%

Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

Rowley

Nagalla

Wang

et al. 2019

Adv Healthcare Materials

120

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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.

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Section: Discussionmentioning

confidence: 99%

Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

Rowley

Nagalla

Wang

et al. 2019

Adv Healthcare Materials

120

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“…An intestinal submucosa ECM-derived scaffold promoted M2 macrophage polarization in a VML model, correlating with increased recruitment of perivascular stem cells and cells with neural markers, and enhanced myotube formation [46]. The correlation of M2 macrophage polarization and ECM-mediated muscle regeneration was shown to depend on Th2 T-cells, which were required to induce a pro-regenerative response [47,48]. Rationally designed biomaterials for modulating inflammatory responses have also been developed.…”

Section: In Situ Skeletal Muscle Tissue Engineeringmentioning

confidence: 99%

Biomaterials for skeletal muscle tissue engineering

Kwee

Mooney

2017

Current Opinion in Biotechnology

157

109

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Although skeletal muscle can naturally regenerate in response to minor injuries, more severe damage and myopathies can cause irreversible loss of muscle mass and function. Cell therapies, while promising, have not yet demonstrated consistent benefit, likely due to poor survival of delivered cells. Biomaterials can improve muscle regeneration by presenting chemical and physical cues to muscle cells that mimic the natural cascade of regeneration. This brief review describes strategies for muscle repair utilizing biomaterials that can provide signals to either transplanted or host muscle cells. These strategies range from approaches that utilize biomaterials alone to those that combine biomaterials with exogenous growth factors, ex vivo cultured cells, and extensive culture time.

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“…The macrophages associated with UBM and IL-4 in the tissue are heterogeneous and distributed in phenotypically distinct clusters. IL-4 is a cytokine recognized for promoting repair of muscle (4), liver (35)., and cartilage (36), and is critical for macrophage polarization in a healing wound (37). The UBM environment induced greater macrophage heterogeneity with two primary terminal subsets with phenotypes relevant to tissue repair.…”

Section: Discussionmentioning

confidence: 99%

Single cell RNA-seq in regenerative and fibrotic biomaterial environments defines new macrophage subsets

Sommerfeld

Cherry

Schwab

et al. 2019

Preprint

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Macrophages play diverse roles in the immune response to infection, cancer, and wound healing where they respond to local environmental signals, yet identification and phenotypic characterization of functional subsets in vivo remains limited. We performed single cell RNA sequencing analysis on differentiated macrophages sorted from a biologic matrix-induced regenerative environment versus a synthetic biomaterial foreign body response (FBR), characterized by TH2/interleukin (IL)-4 and TH17/IL-17, respectively. In the regenerative environment, unbiased clustering and pseudotime analysis revealed distinct macrophage subsets responsible for antigen presentation, chemoattraction, and phagocytosis, as well as a small population with expression profiles of both dendritic cells and skeletal muscle. In the FBR environment, we identified a CD9 hi+ IL-36 + macrophage subset that expressed TH17-associated molecules characteristic of certain auto-immune responses that were virtually absent in mice lacking the IL-17 receptor. Surface marker combinations including CD9 and CD301b defined macrophage fibrotic and regenerative subsets enabling functional assessment and identification in human tissue. Application of the terminal macrophage subsets to train the SingleCellNet algorithm and comparison to human and mouse macrophages in tumor, lung, and liver suggest broad relevance of macrophage classification. These distinct macrophage subsets demonstrate previously unrecognized myeloid phenotypes involved in different tissue responses and provide new targets for potential therapeutic modulation of certain pathologic states and tissue repair.

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The Scaffold Immune Microenvironment: Biomaterial-Mediated Immune Polarization in Traumatic and Nontraumatic Applications

Cited by 72 publications

References 52 publications

Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

Biomaterials for skeletal muscle tissue engineering

Single cell RNA-seq in regenerative and fibrotic biomaterial environments defines new macrophage subsets

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