Dual delivery of IL-10 and AT-RvD1 from PEG hydrogels polarize immune cells towards pro-regenerative phenotypes

Sok, Mary Caitlin P.; Baker, Nusaiba; McClain, Claire A.; Lim, Hong Seo; Turner, Thomas C.; Hymel, Lauren A.; Ogle, Molly E.; Olingy, Claire; Palacios, Joshua I.; García, José R.; Srithar, Krithik; Garcı́a, Andrés J.; Qiu, Peng; Botchwey, Edward A.

doi:10.1016/j.biomaterials.2020.120475

Cited by 32 publications

(21 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[13,14] Furthermore, the antifibrosis effect of IL-10 has previously been revealed both in animal experiments and in clinical trials, where IL-10 wound treatment lowers inflammatory reaction and leads to regeneration through scar-free healing. [15] In vitro coculture models of human fibroblasts and macrophages with IL-10 have also revealed inhibitory effects on proinflammatory cytokine production, deactivation, and even dedifferentiating effects on myofibroblasts. [14] The range of activity of IL-10 is limited to its immediate vicinity.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Microgels Support Proregenerative Macrophage Activation and Attenuate Fibroblast Collagen Synthesis

Mohammadi

Ravanbakhsh

Taheri

et al. 2022

Adv Healthcare Materials

View full text Add to dashboard Cite

Scars composed of fibrous connective tissues are natural consequences of injury upon incisional wound healing in soft tissues. Hydrogels that feature a sustained presentation of immunomodulatory cytokines are known to modulate wound healing. However, existing immunomodulatory hydrogels lack interconnected micropores to promote cell ingrowth. Other limitations include invasive delivery procedures and harsh synthesis conditions that are incompatible with drug molecules. Here, hybrid nanocomposite microgels containing interleukin‐10 (IL‐10) are reported to modulate tissue macrophage phenotype during wound healing. The intercalation of laponite nanoparticles in the polymer network yields microgels with tissue‐mimetic elasticity (Young's modulus in the range of 2–6 kPa) and allows the sustained release of IL‐10 to promote the differentiation of macrophages toward proregenerative phenotypes. The porous interstitial spaces between microgels promote fibroblast proliferation and fast trafficking (an average speed of ≈14.4 µm h−1). The incorporation of hyaluronic acid further enhances macrophage infiltration. The coculture of macrophages and fibroblasts treated with transforming growth factor‐beta 1 resulted in a twofold reduction in collagen‐I production for microgels releasing IL‐10 compared to the IL‐10 free group. The new microgels show potential toward regenerative healing by harnessing the antifibrotic behavior of host macrophages.

show abstract

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Microgels Support Proregenerative Macrophage Activation and Attenuate Fibroblast Collagen Synthesis

Mohammadi

Ravanbakhsh

Taheri

et al. 2022

Adv Healthcare Materials

View full text Add to dashboard Cite

show abstract

“…BM-MSCs have been reported to regulate macrophage phenotype in the context several disorders [ 35 – 37 ]. Recently, using a murine model of diabetic wound healing, Zhang et al demonstrated that BM-MSCs induced the functional restoration of vascular endothelial cells by polarizing macrophages into an anti-inflammatory phenotype [ 38 ]. Cytokines in the inflammatory microenvironment are important in macrophage polarization.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells enhance angiogenesis and promote fat retention in fat grafting via polarized macrophages

et al. 2022

View full text Add to dashboard Cite

Background Fat grafting is one of the most common soft tissue filling methods in plastic surgery. Bone marrow mesenchymal stem cell (BM-MSC) transplantation is an effective method for improving graft retention. However, the role of BM-MSCs in fat transplantation is not completely clear. Methods Human fat particles, together with BM-MSCs or PBS as a control, were subcutaneously transplanted into the backs of nude mice. Samples were taken on days 14, 30 and 90 post-grafting to calculate the fat graft retention rate, and tissue staining was evaluated. Furthermore, macrophages were treated with BM-MSC conditioned medium (BM-MSC-CM) to identify the beneficial component secreted by these stem cells. Results In this study, we found that BM-MSCs improved retention by enhancing angiogenesis in fat grafting. Further analysis revealed that BM-MSCs could significantly inhibit the expression of the proinflammatory M1 macrophage markers interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6 in the early stages of fat grafting and promote the expression of the anti-inflammatory M2 macrophage markers Arg1, IL-10 and VEGF. Furthermore, our results showed that IL-10 secreted by BM-MSCs induced M2 macrophage polarization in vitro. Conclusions BM-MSC transplantation can improve the fat retention rate and promote angiogenesis, which may be related to M2 macrophages. These results help elucidate the role of BM-MSCs in fat grafting.

show abstract

“…[ 227 ] A dual anti‐inflammatory drug delivery system based on PEG was found to promote immune cells toward pro‐regenerative phenotypes. [ 228 ] This hydrogel was crosslinked by cleavable crosslinkers, and loaded with IL‐10 and aspirin‐triggered resolvin‐D1. The release of anti‐inflammatory drugs localized immune suppressive subsets including CD206+ macrophages and IL‐10 expressing dendritic cells to the hydrogel.…”

Section: Strategies To Regulate Immune Responsementioning

confidence: 99%

Toward a Better Regeneration through Implant‐Mediated Immunomodulation: Harnessing the Immune Responses

Zhang

Zhou

et al. 2021

Advanced Science

View full text Add to dashboard Cite

Tissue repair/regeneration, after implantation or injury, involves comprehensive physiological processes wherein immune responses play a crucial role to enable tissue restoration, amidst the immune cells early‐stage response to tissue damages. These cells break down extracellular matrix, clear debris, and secret cytokines to orchestrate regeneration. However, the immune response can also lead to abnormal tissue healing or scar formation if not well directed. This review first introduces the general immune response post injury, with focus on the major immune cells including neutrophils, macrophages, and T cells. Next, a variety of implant‐mediated immunomodulation strategies to regulate immune response through physical, chemical, and biological cues are discussed. At last, various scaffold‐facilitated regenerations of different tissue types, such as, bone, cartilage, blood vessel, and nerve system, by harnessing the immunomodulation are presented. Therefore, the most recent data in biomaterials and immunomodulation is presented here in a bid to shape expert perspectives, inspire researchers to go in new directions, and drive development of future strategies focusing on targeted, sequential, and dynamic immunomodulation elicited by implants.

show abstract

Dual delivery of IL-10 and AT-RvD1 from PEG hydrogels polarize immune cells towards pro-regenerative phenotypes

Cited by 32 publications

References 64 publications

Immunomodulatory Microgels Support Proregenerative Macrophage Activation and Attenuate Fibroblast Collagen Synthesis

Immunomodulatory Microgels Support Proregenerative Macrophage Activation and Attenuate Fibroblast Collagen Synthesis

Bone marrow mesenchymal stem cells enhance angiogenesis and promote fat retention in fat grafting via polarized macrophages

Toward a Better Regeneration through Implant‐Mediated Immunomodulation: Harnessing the Immune Responses

Contact Info

Product

Resources

About