Photocrosslinkable Gelatin Hydrogels Modulate the Production of the Major Pro-inflammatory Cytokine, TNF-α, by Human Mononuclear Cells

Donaldson, Amy R.; Tanase, Constantin Edi; Awuah, Dennis; Bathrinarayanan, Pranav Vasanthi; Hall, Laurence S.; Nikkhah, Mehdi; Khademhosseini, Ali; Rose, Felicity R. A. J.; Alexander, Cameron; Ghaemmaghami, Amir M.

doi:10.3389/fbioe.2018.00116

Cited by 43 publications

(37 citation statements)

References 53 publications

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“…This finding is consistent with the results of previous studies, in which the addition of small molecules (e.g. growth factors, cytokines, peptides) had negligible effects on the mechanical properties of the hydrogel 38,66,67 . Future studies are needed to assess further the impact of biomaterials that have stronger mechanical support and can simultaneously provide an optimal immunomodulatory environment.…”

Section: Discussionsupporting

confidence: 93%

Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival

Uehara

Sheikhi

et al. 2019

Sci Rep

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A primary goal in the management of burn wounds is early wound closure. The use of skin allografts represents a lifesaving strategy for severe burn patients, but their ultimate rejection limits their potential efficacy and utility. IL-6 is a major pleiotropic cytokine which critically links innate and adaptive immune responses. Here, we devised anti-IL-6 receptor eluting gelatin methacryloyl (GelMA) biomaterials (GelMA/anti-IL-6), which were implanted at the interface between the wound beds and skin allografts. Our visible light crosslinked GelMA/anti-IL-6 immunomodulatory biomaterial (IMB) demonstrated a stable kinetic release profile of anti-IL-6. In addition, the incorporation of anti-IL-6 within the GelMA hydrogel had no effect on the mechanical properties of the hydrogels. Using a highly stringent skin transplant model, the GelMA/anti-IL-6 IMB almost doubled the survival of skin allografts. The use of GelMA/anti-IL-6 IMB was far superior to systemic anti-IL-6 receptor treatment in prolonging skin allograft survival. As compared to the untreated control group, skin from the GelMA/anti-IL-6 IMB group contained significantly fewer alloreactive T cells and macrophages. Interestingly, the environmental milieu of the draining lymph nodes (DLNs) of the mice implanted with the GelMA/anti-IL-6 IMB was also considerably less pro-inflammatory. The percentage of CD4 + IFNγ + cells was much lower in the DLNs of the GelMA/anti-IL-6 IMB group in comparison to the GelMA group. These data highlight the importance of localized immune delivery in prolonging skin allograft survival and its potential utility in treating patients with severe burns.

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Section: Discussionsupporting

confidence: 93%

Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival

Uehara

Sheikhi

et al. 2019

Sci Rep

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“…Crosslinking of gelatin can be achieved by adding a photosensitive methacryloyl group to gelatin molecules (gelatin methacryloyl, GelMA) and offers the ability to tune gelatin crosslinking with light. Using this method, Donaldson et al created collagen‐based materials with varied stiffness and topological patterns, and explored the mechanism underlying their effects on monocyte/macrophage behavior . Human peripheral monocytes cultured on hydrogels made of GelMA exhibited lower inflammatory Tnfα gene expression 30 min and 4 h after lipopolysaccharide (LPS) stimulation, when compared to cells cultured on tissue culture plastic.…”

Section: Immunomodulation By Naturally Derived Ecmsmentioning

confidence: 99%

Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

Rowley

Nagalla

Wang

et al. 2019

Adv Healthcare Materials

135

123

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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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“…In previous work, we have shown how semi-synthetic hydrogels prepared from PEG and heparin GAGs represent a platform for TME modeling ( Bray et al, 2015 ). Likewise, hydrogels formed from gelatin-methacryloyl (GelMA) have been used to successfully recapitulate breast cancer invasion and chemoresponses in vitro ( Yue et al, 2015 ; Loessner et al, 2016 ; Donaldson et al, 2018 ; Meinert et al, 2018 ). Exploiting such biohybrid 3D matrices allows for the control of batch-to-batch physicochemical properties, which are known to affect cellular behavior in the TME.…”

Section: Discussionmentioning

confidence: 99%

Three-Dimensional Models as a New Frontier for Studying the Role of Proteoglycans in the Normal and Malignant Breast Microenvironment

Clegg

Koch

Thompson

et al. 2020

Front. Cell Dev. Biol.

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The extracellular matrix (ECM) provides cues to direct mammogenesis, tumourigenesis and metastatic processes. Over the past several decades, two-dimensional (2D) culture models have been invaluable in furthering our understanding of the tumor microenvironment (TME), however, they still do not accurately emulate the associated biological complexities. In contrast, three-dimensional (3D) culture models provide a more physiologically relevant platform to study relevant physicochemical signals, stromal-epithelial cell interactions, vascular and immune components, and cell-ECM interactions in the human breast microenvironment. A common thread that may weave these multiple interactions are the proteoglycans (PGs), a prominent family of molecules in breast tissue. This review will discuss how these PGs contribute to the breast cancer TME and provide a summary of the traditional and emerging technologies that have been utilized to better understand the role of PGs during malignant transformation. Furthermore, this review will emphasize the differences that PGs exhibit between normal tissues and tumor ECM, providing a rationale for the investigation of underexplored roles of PGs in breast cancer progression using state-of-the-art 3D culture models.

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Photocrosslinkable Gelatin Hydrogels Modulate the Production of the Major Pro-inflammatory Cytokine, TNF-α, by Human Mononuclear Cells

Cited by 43 publications

References 53 publications

Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival

Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival

Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

Three-Dimensional Models as a New Frontier for Studying the Role of Proteoglycans in the Normal and Malignant Breast Microenvironment

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