KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats

Yang, Xuanxin; Yang, Rongshuai; Chen, Min; Zhou, Qingde; Zheng, Yingying; Lü, Chen; Bi, Jianing; Sun, Wenzhe; Huang, Tongzhou; Li, Lijia; Gong, Jianxiang; Li, Xiaokun; Qi, Hui; Wang, Xiaojie

doi:10.1136/bmjdrc-2019-001009

Cited by 34 publications

(26 citation statements)

References 39 publications

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“…Of note, several studies demonstrated local tolerance to p407 poloxamer hydrogel when tested on the skin, including the burnt skin [ 22 , 34 ]. Moreover, a number of studies used a poloxamer hydrogel as a vehicle for bioactive molecules aimed at promoting skin healing [ 21 , 34 , 35 , 36 , 37 , 38 ]. These various studies highlighted the value of using a poloxamer hydrogel as a delivery system for an active ingredient.…”

Section: Discussionmentioning

confidence: 99%

“…However, it should be noted that, in the abovementioned works, the impact of poloxamer hydrogel alone was not assessed. Indeed, to our knowledge, only one study tested the potential toxicity of p407 poloxamer hydrogel on skin cells [ 38 ], more specifically, the fibroblastic murine cell line NIH 3T3. In this regard, we present the first in-depth analysis of the impact exerted by p407/p188 poloxamer hydrogel on the healing process of cultured human skin explants.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of a Topically Testable Model of Burn Injury on Human Skin Explants

Gross-Amat

Guillen

Salmon

et al. 2020

IJMS

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Severe burn injuries remain a major health problem due to high rates of mortality, residual morbidity, and/or aesthetic damages. To find new therapies aimed at promoting a harmonious healing of skin burns, it is important to develop models which take into account the unique properties of the human skin. Based on previously described models of burn injury performed on human skin explants, we hypothesized that maintaining explants under constant tension forces would allow to more closely reproduce the pathophysiological processes of skin remodeling. We thus. Here, we set up and characterized an improved model of deep second-degree burn injury on ex vivo cultured human skin explants at air-liquid interface and maintained under conditions of constant tension forces. A spontaneous re-epithelialization of the lesion was observed 8 to 9 days post burn and was found to rely on the proliferation of basal keratinocytes at the wound edges. Collagen VII at the dermo-epidermal junction reformed along with the progression of re-epithelializatio and a synthesis of procollagen III was observed in the dermis at the wound site. These findings indicate that our model is suitable for the assessment of clinically-relevant therapies aimed at modulating the kinetics of re-epithelialization and/or the activation of fibroblasts following skin burn injuries. In this regard, we evaluated the use of a thermoreversible poloxamer hydrogel as a vehicle for topically-testable therapeutic molecules. Our data showed that, although useful for drug formulation, the p407/p188 poloxamer hydrogel induces a delay of skin re-epithelialization in humans skin explants submitted to experimental burn injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization of a Topically Testable Model of Burn Injury on Human Skin Explants

Gross-Amat

Guillen

Salmon

et al. 2020

IJMS

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“…In addition, it was found that FGF-21 inhibited the formation of NLRP 3 inflammatory body in vascular smooth muscle cells under hyperglycemia stress through FGFR 1, and inhibit the formation of NLRP 3 inflammatory body in vascular smooth muscle cells by inhibiting the dephosphorylation of Syk tyrosine 525 ( 109 ). FGF-21 as also been studied to regulate wound inflammatory response, and FGF-21 can reduce excessive inflammatory response in rat skin and promote the transformation of inflammatory phase into proliferative phase by up-regulating IL-10, down-regulating IL-6, IL-1β and TNF-α ( 110 ).…”

Section: Fgf-21 and Diabetic Wound Healingmentioning

confidence: 99%

Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects

Liu

Deng

et al. 2021

Front. Endocrinol.

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Diabetic foot ulcer (DFU) is a combination of neuropathy and various degrees of peripheral vasculopathy in diabetic patients resulting in lower extremity infection, ulcer formation, and deep-tissue necrosis. The difficulty of wound healing in diabetic patients is caused by a high glucose environment and various biological factors in the patient. The patients’ skin local microenvironment changes and immune chemotactic response dysfunction. Wounds are easy to be damaged and ulcerated repeatedly, but difficult to heal, and eventually develop into chronic ulcers. DFU is a complex biological process in which many cells interact with each other. A variety of growth factors released from wounds are necessary for coordination and promotion of healing. Fibroblast growth factor (FGF) is a family of cell signaling proteins, which can mediate various processes such as angiogenesis, wound healing, metabolic regulation and embryonic development through its specific receptors. FGF can stimulate angiogenesis and proliferation of fibroblasts, and it is a powerful angiogenesis factor. Twenty-three subtypes have been identified and divided into seven subfamilies. Traditional treatments for DFU can only remove necrotic tissue, delay disease progression, and have a limited ability to repair wounds. In recent years, with the increasing understanding of the function of FGF, more and more researchers have been applying FGF-1, FGF-2, FGF-4, FGF-7, FGF-21 and FGF-23 topically to DFU with good therapeutic effects. This review elaborates on the recently developed FGF family members, outlining their mechanisms of action, and describing their potential therapeutics in DFU.

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“…A lack of FGF7 could further delay cutaneous wound healing in diabetic mice. In diabetic rats, FGF10 enhanced wound repair of scalded skin together with FGF21 [ 199 ]. With novel delivery strategies that improve skin penetration, FGF10 was shown to inhibit ER stress and promote keratinocyte proliferation, accelerating wound healing and hair growth [ 200 , 201 ].…”

Section: Reviewmentioning

confidence: 99%

Roles of the fibroblast growth factor signal transduction system in tissue injury repair

et al. 2022

Self Cite

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Following injury, tissue autonomously initiates a complex repair process, resulting in either partial recovery or regeneration of tissue architecture and function in most organisms. Both the repair and regeneration processes are highly coordinated by a hierarchy of interplay among signal transduction pathways initiated by different growth factors, cytokines and other signaling molecules under normal conditions. However, under chronic traumatic or pathological conditions, the reparative or regenerative process of most tissues in different organs can lose control to different extents, leading to random, incomplete or even flawed cell and tissue reconstitution and thus often partial restoration of the original structure and function, accompanied by the development of fibrosis, scarring or even pathogenesis that could cause organ failure and death of the organism. Ample evidence suggests that the various combinatorial fibroblast growth factor (FGF) and receptor signal transduction systems play prominent roles in injury repair and the remodeling of adult tissues in addition to embryonic development and regulation of metabolic homeostasis. In this review, we attempt to provide a brief update on our current understanding of the roles, the underlying mechanisms and clinical application of FGFs in tissue injury repair.

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KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats

Cited by 34 publications

References 39 publications

Characterization of a Topically Testable Model of Burn Injury on Human Skin Explants

Characterization of a Topically Testable Model of Burn Injury on Human Skin Explants

Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects

Roles of the fibroblast growth factor signal transduction system in tissue injury repair

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