Controlled release strategies for modulating immune responses to promote tissue regeneration

Park, Jonghyuck; Shea, Lonnie D.

doi:10.1016/j.jconrel.2015.08.014

Cited by 43 publications

(29 citation statements)

References 181 publications

(208 reference statements)

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“…This difference was not significant. IL-10 has been extensively revered as an anti-inflammatory cytokine capable of shifting the phenotype of macrophages 22,[44][45][46][47][48] and these studies support the previous findings.…”

Section: Il-10+nt-3 Improves Forelimb Locomotor Recoverysupporting

confidence: 87%

PLG Bridge Implantation in Chronic SCI Promotes Axonal Elongation and Myelination

Smith

Ciciriello

Guo

et al. 2019

ACS Biomater. Sci. Eng.

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One million estimated cases of spinal cord injury (SCI) have been reported in the United States and repairing an injury has constituted a difficult clinical challenge. The complex, dynamic, inhibitory microenvironment post injury, which is characterized by pro-inflammatory signaling from invading leukocytes and lack of sufficient factors that promote axonal survival and elongation, limits regeneration. Herein, we investigated the delivery of polycistronic vectors, which have the potential to co-express factors that target distinct barriers to regeneration, from a multiple channel PLG bridge to enhance spinal cord regeneration. In the present study, we investigated polycistronic delivery of IL-10, that targets pro-inflammatory signaling, and NT-3 that targets axonal survival and elongation. A significant increase was observed in the density of regenerative macrophages for IL-10+NT-3 condition relative to conditions without IL-10. Furthermore, combined delivery of IL-10+NT-3 produced a significant increase of axonal density and notably myelinated axons compared to all other conditions. A significant increase in functional recovery was observed for IL-10+NT-3 delivery at 12 wpi that was positively correlated to oligodendrocyte myelinated axon density, suggesting oligodendrocyte-mediated myelination as an important target to improve functional recovery. These results further support the use of multiple channel PLG bridges as a growth supportive substrate and platform to deliver bioactive agents to modulate the SCI microenvironment and promote regeneration and functional recovery.

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Section: Il-10+nt-3 Improves Forelimb Locomotor Recoverysupporting

confidence: 87%

PLG Bridge Implantation in Chronic SCI Promotes Axonal Elongation and Myelination

Smith

Ciciriello

Guo

et al. 2019

ACS Biomater. Sci. Eng.

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“…When innate immune cells are activated in the blood and spleen, they have high phagocytic capacity for scavenging apoptotic cells, cellular debris, and foreign invasive materials (24,25). Generally, NPs may be perceived by inflammatory monocytes and neutrophils as foreign material and are then rapidly internalized (13,26,27). The rapid infiltration of various immune cells including inflammatory monocytes and neutrophils into the SCI leads to inflammatory response-derived secondary damage, contributing to further neuronal cell death, axonal dieback, demyelination, and scar tissue formation (4,28).…”

Section: Discussionmentioning

confidence: 99%

Intravascular innate immune cells reprogrammed via intravenous nanoparticles to promote functional recovery after spinal cord injury

Park

Zhang

Saito

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Traumatic primary spinal cord injury (SCI) results in paralysis below the level of injury and is associated with infiltration of hematogenous innate immune cells into the injured cord. Methylprednisolone has been applied to reduce inflammation following SCI, yet was discontinued due to an unfavorable risk-benefit ratio associated with off-target effects. In this study, i.v. administered poly(lactide-coglycolide) nanoparticles were internalized by circulating monocytes and neutrophils, reprogramming these cells based on their physicochemical properties and not by an active pharmaceutical ingredient, to exhibit altered biodistribution, gene expression, and function. Approximately 80% of nanoparticle-positive immune cells were observed within the injury, and, additionally, the overall accumulation of innate immune cells at the injury was reduced 4-fold, coinciding with down-regulated expression of proinflammatory factors and increased expression of antiinflammatory and proregenerative genes. Furthermore, nanoparticle administration induced macrophage polarization toward proregenerative phenotypes at the injury and markedly reduced both fibrotic and gliotic scarring 3-fold. Moreover, nanoparticle administration with the implanted multichannel bridge led to increased numbers of regenerating axons, increased myelination with about 40% of axons myelinated, and an enhanced locomotor function (score of 6 versus 3 for control group). These data demonstrate that nanoparticles provide a platform that limits acute inflammation and tissue destruction, at a favorable risk-benefit ratio, leading to a proregenerative microenvironment that supports regeneration and functional recovery. These particles may have applications to trauma and potentially other inflammatory diseases.

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“…The design of biomaterials to specifically modulate macrophage behavior has emerged as a promising strategy in regenerative medicine and tissue engineering (see refs. ), including utilization of controlled release systems or microRNA‐focused techniques . Here we highlight key studies that have modified biomaterial surfaces and structures to control both macrophage and fibroblast behavior along with combination strategies that include delivery of soluble factors through the use of coatings, films, electrospinning, liposomes, and polymeric particles.…”

Section: Strategies For Modulating Macrophage and Fibroblast Behaviormentioning

confidence: 99%

Macrophage and Fibroblast Interactions in Biomaterial‐Mediated Fibrosis

Witherel

Abebayehu

Barker

et al. 2019

Adv Healthcare Materials

276

201

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Biomaterial‐mediated inflammation and fibrosis remain a prominent challenge in designing materials to support tissue repair and regeneration. Despite the many biomaterial technologies that have been designed to evade or suppress inflammation (i.e., delivery of anti‐inflammatory drugs, hydrophobic coatings, etc.), many materials are still subject to a foreign body response, resulting in encapsulation of dense, scar‐like extracellular matrix. The primary cells involved in biomaterial‐mediated fibrosis are macrophages, which modulate inflammation, and fibroblasts, which primarily lay down new extracellular matrix. While macrophages and fibroblasts are implicated in driving biomaterial‐mediated fibrosis, the signaling pathways and spatiotemporal crosstalk between these cell types remain loosely defined. In this review, the role of M1 and M2 macrophages (and soluble cues) involved in the fibrous encapsulation of biomaterials in vivo is investigated, with additional focus on fibroblast and macrophage crosstalk in vitro along with in vitro models to study the foreign body response. Lastly, several strategies that have been used to specifically modulate macrophage and fibroblast behavior in vitro and in vivo to control biomaterial‐mediated fibrosis are highlighted.

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Controlled release strategies for modulating immune responses to promote tissue regeneration

Cited by 43 publications

References 181 publications

PLG Bridge Implantation in Chronic SCI Promotes Axonal Elongation and Myelination

PLG Bridge Implantation in Chronic SCI Promotes Axonal Elongation and Myelination

Intravascular innate immune cells reprogrammed via intravenous nanoparticles to promote functional recovery after spinal cord injury

Macrophage and Fibroblast Interactions in Biomaterial‐Mediated Fibrosis

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