Immunomodulatory biomaterial-based wound dressings advance the healing of chronic wounds via regulating macrophage behavior

Sousa, Ana Beatriz; Águas, Artur P.; Barbosa, Mário A.; Barbosa, Judite N.

doi:10.1093/rb/rbac065

Cited by 24 publications

(16 citation statements)

References 77 publications

(99 reference statements)

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“… 12 Meanwhile, phagocytosis of apoptotic neutrophils is essential for transforming the macrophage phenotype to an anti-inflammatory phenotype(M2). 57 In summary, the phagocytosis of macrophages and their phenotypic conversion complement each other and promote each other in the process of wound healing. Furthermore, a previous publication reported that exosomes from MSCs treated with LPS highly expressed let-7b, promoting wound healing by activating M2-type macrophages and down-regulating inflammatory factor.…”

Section: Discussionmentioning

confidence: 99%

Human Keratinocyte-Derived Exosomal MALAT1 Promotes Diabetic Wound Healing by Upregulating MFGE8 via microRNA-1914-3p

Kuang¹,

Zhang²,

Li³

et al. 2023

IJN

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Purpose Diabetic wound is a highly prevalent and refractory disease. Extensive studies have confirmed that keratinocytes and macrophages play an important role in the process of wound healing. Additionally, exosomes are regarded as a vital intercellular communication tool. This study aimed to investigate the role of human keratinocyte-derived exosomal MALAT1 in the treatment of diabetic wound by influencing the biological function of macrophages. Methods We mainly assessed the function of MALAT1 on the biological changes of macrophages, and the expression of MALAT1 in the keratinocyte-exosomes analyzed by quantitative real-time polymerase chain reaction (RT-qPCR). The downstream interaction between RNAs or proteins was assessed by mechanistic experiments. Besides, we evaluated the effects of human keratinocyte-derived exosomal MALAT1 on diabetic wound healing in vivo to verify in vitro results. Results We demonstrated that human keratinocyte-derived exosomal MALAT1 enhanced the biological functions of high glucose-injured macrophages, including phagocytosis, converting to a pro-healing phenotype and reducing apoptosis. Mechanistically, MALAT1 accelerated the expression of MFGE8 by competitively binding to miR-1914-3p, thereby affecting the function of macrophages and the signal axis of TGFB1/SMAD3, and finally promoting the healing of diabetic wounds. Human keratinocyte-derived exosomal MALAT1 might promote collagen deposition, ECM remodeling, and expression of MFGE8, VEGF, and CD31 but reduce the expression of TGFB and SMAD3 in an in vivo model of diabetic mice wounds, which accelerated diabetic wound healing and restored its function. Conclusion The current study revealed that human keratinocyte-derived exosomal MALAT1 would suppress miR-1914-3p to activate MFGE8 and eventually promote wound healing by enhancing macrophage phagocytosis, converting to a pro-healing phenotype and reducing apoptosis. It proposed that keratinocyte-derived exosomes might have the capacity to serve as a new method for the clinical treatment of diabetic wound.

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Section: Discussionmentioning

confidence: 99%

Human Keratinocyte-Derived Exosomal MALAT1 Promotes Diabetic Wound Healing by Upregulating MFGE8 via microRNA-1914-3p

Kuang¹,

Zhang²,

Li³

et al. 2023

IJN

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“…Macrophages transition into an anti-inflammatory phenotype as DAMPs and pathogen-associated molecular patterns (PAMPs) decrease, preparing them for the next healing phase. [34,39,40]…”

Section: Inflammationmentioning

confidence: 99%

Extracellular Matrix‐Bioinspired Anisotropic Topographical Cues of Electrospun Nanofibers: A Strategy of Wound Healing through Macrophage Polarization

Park,

Patil,

Dutta

et al. 2024

Adv Healthcare Materials

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The skin serves as the body's outermost barrier and is the largest organ, providing protection not only to the body but also to various internal organs. Owing to continuous exposure to various external factors, it is susceptible to damage that can range from simple to severe, including serious types of wounds such as burns or chronic wounds. Macrophages play a crucial role in the entire wound healing process and contribute significantly to skin regeneration. Initially, M1 macrophages infiltrate to phagocytose bacteria, debris, and dead cells in fresh wounds. As tissue repair is activated, M2 macrophages are promoted, reducing inflammation and facilitating restoration of the dermis and epidermis to regenerate the tissue. Based on this understanding, developing extracellular matrix (ECM) mimicking structures is suitable for promoting cell attachment, proliferation, migration, and macrophage polarization. Among the numerous strategies, electrospinning is a versatile technique for obtaining ECM‐mimicking structures with anisotropic and isotropic topologies of micro/nanofibers. The use of various biomaterials in the fabrication of nanofibers with anisotropic and isotropic topologies can influence macrophage polarization. Moreover, these fibers possess a high surface‐area‐to‐volume ratio, promoting the effective exchange of vital nutrients and oxygen, which are crucial for cell viability and tissue regeneration. Micro/nanofibers with diverse physical and chemical properties can be tailored to polarize macrophages toward skin regeneration and wound healing, depending on specific requirements. This review describes the significance of micro/nano structures for activating macrophages and promoting wound healing.This article is protected by copyright. All rights reserved

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“…[ 2 , 26 ]. Chronic wounds are often characterized by a prolonged period of inflammatory response, delayed cell proliferation, less angiogenesis, and inadequate re-epithelialization and remodeling [ 27 ]. Treatment of chronic wounds mainly consists in preserving the moist of wound, controlling infection, and removing necrotic tissue [ 28 ].…”

Section: The Process Of Wound Healingmentioning

confidence: 99%

Application of Biomedical Microspheres in Wound Healing

Yang

Zhang

Gan

et al. 2023

IJMS

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Tissue injury, one of the most common traumatic injuries in daily life, easily leads to secondary wound infections. To promote wound healing and reduce scarring, various kinds of wound dressings, such as gauze, bandages, sponges, patches, and microspheres, have been developed for wound healing. Among them, microsphere-based tissue dressings have attracted increasing attention due to the advantage of easy to fabricate, excellent physicochemical performance and superior drug release ability. In this review, we first introduced the common methods for microspheres preparation, such as emulsification-solvent method, electrospray method, microfluidic technology as well as phase separation methods. Next, we summarized the common biomaterials for the fabrication of the microspheres including natural polymers and synthetic polymers. Then, we presented the application of the various microspheres from different processing methods in wound healing and other applications. Finally, we analyzed the limitations and discussed the future development direction of microspheres in the future.

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Immunomodulatory biomaterial-based wound dressings advance the healing of chronic wounds via regulating macrophage behavior

Cited by 24 publications

References 77 publications

Human Keratinocyte-Derived Exosomal MALAT1 Promotes Diabetic Wound Healing by Upregulating MFGE8 via microRNA-1914-3p

Human Keratinocyte-Derived Exosomal MALAT1 Promotes Diabetic Wound Healing by Upregulating MFGE8 via microRNA-1914-3p

Extracellular Matrix‐Bioinspired Anisotropic Topographical Cues of Electrospun Nanofibers: A Strategy of Wound Healing through Macrophage Polarization

Application of Biomedical Microspheres in Wound Healing

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