Stabilized Interleukin-4-Loaded Poly(lactic-<i>co</i>-glycolic) Acid Films Shift Proinflammatory Macrophages toward a Regenerative Phenotype<i>in Vitro</i>

Ziemba, Alexis M.; D’Amato, Anthony R.; MacEwen, Taylor M; Puhl, Devan L; Koppes, Abigail N.; Koppes, Ryan A.; Lennartz, Michelle R.; Gilbert, Ryan J.

doi:10.1021/acsabm.8b00769

Cited by 12 publications

(13 citation statements)

References 69 publications

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“…M2 macrophages also produce VEGFA, TGF-β and IL-8, which are responsible for angiogenesis and lymphangiogenesis, which also are essential for tissue and wound healing [39]. M2 macrophages can be further divided into three subtypes: M2a, M2b and M2c, and each subtype performs different functions [40][41][42]. M2a-type macrophages are induced by IL-4 or IL-13, promote cell growth and tissue repair [41].…”

Section: M2: Alternatively Activated Macrophagesmentioning

confidence: 99%

“…M2 macrophages can be further divided into three subtypes: M2a, M2b and M2c, and each subtype performs different functions [40][41][42]. M2a-type macrophages are induced by IL-4 or IL-13, promote cell growth and tissue repair [41]. M2b-type macrophages are induced by immune complex or LPS/IL-1 stimulation, suppress acute inflammatory response.…”

Section: M2: Alternatively Activated Macrophagesmentioning

confidence: 99%

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Lactic acid in macrophage polarization: The significant role in inflammation and cancer

Zhou

Yan

et al. 2021

International Reviews of Immunology

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Metabolite lactic acid has always been regarded as a metabolic by-product rather than a bioactive molecule. Recently, this view has changed since it was discovered that lactic acid can be used as a signal molecule and has novel signal transduction functions both intracellular and extracellular, which can regulate key functions in the immune system. in recent years, more and more evidence has shown that lactic acid is closely related to the metabolism and polarization of macrophages. During inflammation, lactic acid is a regulator of macrophage metabolism, and it can prevent excessive inflammatory responses; in malignant tumors, lactic acid produced by tumor tissues promotes the polarization of tumor-associated macrophages, which in turn promotes tumor progression. in this review, we examined the relationship between lactic acid and macrophage metabolism. we further discussed how lactic acid plays a role in maintaining the homeostasis of macrophages, as well as the biology of macrophage polarization and the M1/M2 imbalance in human diseases. Potential methods to target lactic acid in the treatment of inflammation and cancer will also be discussed so as to provide new strategies for the treatment of diseases.

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Section: M2: Alternatively Activated Macrophagesmentioning

confidence: 99%

Section: M2: Alternatively Activated Macrophagesmentioning

confidence: 99%

Lactic acid in macrophage polarization: The significant role in inflammation and cancer

Zhou

Yan

et al. 2021

International Reviews of Immunology

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“…IL-4 introduction on the scaffold could be carried out using both noncovalent loading and covalent conjugation. In the former approach, scaffolds could be either loaded with cytokines/drugs prior to the fabrication 74 or the functional molecules could be adsorbed on the surface after the production. 75 Both approaches facilitate the release of functional molecules over time to elicit their effect.…”

Section: ■ Discussionmentioning

confidence: 99%

Inducing Immunomodulatory Effects on Human Macrophages by Multifunctional NCO-sP(EO-stat-PO)/Gelatin Hydrogel Nanofibers

Taskin¹,

Tylek²,

Blum³

et al. 2021

ACS Biomater. Sci. Eng.

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Endowing materials and scaffolds with immunomodulatory properties has evolved into a very active field of research. However, combining such effects with multifunctionality regarding cell adhesion and manipulation is still challenging due to the intricate nature of cell–substrate interactions that require fine-tuning of scaffold properties. Here, we reported electrospinning of a well-known biopolymer, gelatin, together with six-arm star-shaped poly(ethylene oxide-stat-propylene oxide) prepolymer with isocyanate end groups (NCO-sP(EO-stat-PO)) as a reactive prepolymer cross-linker. Covalent coupling of two components during and after processing yielded a network of hydrogel fibers that was remarkably stable under aqueous and also proteolytic conditions without the need for extra cross-linking, with a significant increase in stability with increasing NCO-sP(EO-stat-PO) content. When seeded with human macrophages, cells adhered and spread on the fibers and were found highly viable after 7 days of culture across all scaffolds. Furthermore, hybrid fibrous meshes upregulated the expression of a prohealing gene, CD206, while downregulating proinflammatory genes, IL-1β and IL-8. Markedly, NCO-sP(EO-stat-PO)-rich samples induced a significantly reduced release of proinflammatory cytokines, IL-1β, IL-6, and IL-8. Finally, we successfully conjugated IL-4 to NCO-sP(EO-stat-PO) that effectively steered macrophages into a prohealing M2 type, demonstrating additional and robust control over the immunomodulatory feature of the scaffolds.

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“…They clear the wound and establish a temporary matrix during the inflammatory phase. [ 15–18 ] Over time, anti‐inflammatory or M2‐like macrophage subtypes gradually dominate, triggering the proliferation phase. [ 19 ]…”

Section: Introductionmentioning

confidence: 99%

Advanced Biomaterials for Regulating Polarization of Macrophages in Wound Healing

Mao

Chen

Cai

et al. 2021

Adv Funct Materials

120

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Macrophage immunotherapy is an emerging treatment strategy that modulates the immune system to promote wound healing. The functionality and regeneration of tissue depend on spatially and temporally regulating the biophysical and biochemical microenvironmental with poorly understood mechanisms. Biomaterials are carefully crafted to display and deliver macrophage regulatory signals in a precise and near‐physiological way, serving as powerful artificial microenvironments in which to explore and direct the fate of macrophages. The review starts with discussing the classification and function of macrophages, and then introduces the polarization of macrophages in different microenvironments of conventional wounds and chronic wounds. Recent advances in biomaterials that balance the phenotypes of macrophages in wound healing are emphasized. Finally, looking ahead, the potential ability of biomaterial scaffolds to modulate immune signaling to produce an environment conducive to regeneration is discussed.

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Stabilized Interleukin-4-Loaded Poly(lactic-co-glycolic) Acid Films Shift Proinflammatory Macrophages toward a Regenerative Phenotypein Vitro

Cited by 12 publications

References 69 publications

Lactic acid in macrophage polarization: The significant role in inflammation and cancer

Lactic acid in macrophage polarization: The significant role in inflammation and cancer

Inducing Immunomodulatory Effects on Human Macrophages by Multifunctional NCO-sP(EO-stat-PO)/Gelatin Hydrogel Nanofibers

Advanced Biomaterials for Regulating Polarization of Macrophages in Wound Healing

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