SIKVAV promotion proliferation of vascular endothelial cells and related mechanisms.

BACKGROUND: Vascular endothelial injury, a key factor in diabetic foot ulcers (DFUs) pathogenesis, is linked to the impaired proliferation and migration of vascular endothelial cells, modulated by hypoxia-inducible factor, growth factors, and inflammatory elements. OBJECTIVE: The present study assesses the role of SIKVAV (Ser-Ile-Lys-Val-Ala-Val), a peptide shown to enhance cell proliferation and migration, on mouse aortic endothelial cell (MAEC) and the corresponding molecular mechanisms. METHODS: MAEC were treated with SIKVAV at 0, 100, 200, 400, and 600 µg/mL for 0, 24, 48, and 72 h. Cell viability was tested using the CCK-8 assay. Proliferating cell nuclear antigen (PCNA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (Akt) levels were measured by qRT-PCR and western blot. RESULTS: SIKVAV augmented PCNA mRNA expression and stimulated vascular endothelial cell proliferation in a concentration and time-dependent fashion. Furthermore, it amplified the expression of p-ERK1/2 and p-Akt, pivotal components of the mitogen-activated protein kinase (MAPK)/ERK1/2 and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. The inhibition of these pathways suppressed PCNA mRNA expression, cell proliferation rate, and decreased p-ERK1/2 and p-Akt levels, highlighting SIKVAV's role in promoting vascular endothelial cell proliferation via these pathways. CONCLUSION: The results of this study confirmed that SIKVAV grafted onto scaffolds can accelerate the proliferation of vascular endothelial cells for the therapy of skin wounds, and provide a theoretical basis for its application in ischemic disease as synthesized biomaterials scaffolds of tissue engineering.

The role of gel wound dressings loaded with stem cells in the treatment of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are a serious complication of diabetes and the main cause of nontraumatic lower limb amputations, resulting in a serious economic burden on society. The main causes of DFUs include peripheral neuropathy, foot deformity, chronic inflammation, and peripheral artery disease. There are many clinical approaches for the treatment of DFUs, but they are all aimed at addressing a single aetiological factor. Stem cells (SCs), which express many cytokines and a variety of nerve growth factors and modulate immunological function in the wound, may accelerate DFU healing by promoting angiogenesis, cell proliferation, and nerve growth and regulating the inflammatory response. However, the survival time of SCs without scaffold support in the wound is short. Multifunctional gel wound dressings play a critical role in skin wound healing due to their ability to maintain SC survival for a long time, provide moisture and prevent electrolyte and water loss in DFUs. Among the many methods for clinical treatment of DFUs, the most successful one is therapy with gel dressings loaded with SCs. To accelerate DFU healing, gel wound dressings loaded with SCs are needed to promote the survival and migration of SCs and increase wound contraction. This review summarizes the research advancements regarding multifunctional gel wound dressings and SCs in the treatment of DFU to demonstrate the effectiveness and safety of this combinational therapeutic strategy.

SIKVAV-Modified Chitosan Hydrogel as a Skin Substitutes for Wound Closure in Mice.

Skin wound healing is a complex and dynamic process that involves angiogenesis and growth factor secretion. Newly formed vessels can provide nutrition and oxygen for skin wound healing. Growth factors in skin wounds are important for keratinocytes and fibroblasts proliferation, epithelialization, extracellular matrix remodeling, and angiogenesis, which accelerate skin wound healing. Therefore, treatment strategies that enhance angiogenesis and growth factors secretion in skin wounds can accelerate skin wound healing. This study investigated the effects of a SIKVAV (Ser-Ile-Lys-Val-Ala-Val) peptide-modified chitosan hydrogel on skin wound healing. Hematoxylin and eosin (H&E) staining demonstrated that the SIKVAV-modified chitosan hydrogel accelerated the re-epithelialization of wounds compared with that seen in the negative and positive controls. Masson's trichrome staining showed that more collagen fibers were deposited in the skin wounds treated with the SIKVAV-modified chitosan hydrogel than in the negative and positive controls. Immunohistochemistry assays demonstrated that more myofibroblasts were deposited and more angiogenesis occurred in skin wounds treated with the SIKVAV-modified chitosan hydrogel than in the negative and positive controls. In addition, ELISA assays showed that the SIKVAV-modified chitosan hydrogels promoted the secretion of growth factors in skin wounds. Taken together, these results suggest that the SIKVAV-modified chitosan hydrogel has the potential to be developed as synthesized biomaterials for the treatment of skin wounds.

Peptide SIKVAV-modified chitosan hydrogels promote skin wound healing by accelerating angiogenesis and regulating cytokine secretion.

Skin wound healing is complex and involves the processes of many factors, among which angiogenesis and inflammatory responses play important roles. New blood vessels provide nutrition and oxygen for skin wound repair. Cytokines in skin wounds, which include pro-inflammatory and anti-inflammatory factors, can modulate the inflammatory response. Therefore, treatment strategies that promote angiogenesis and modulate the inflammatory response in skin wounds can accelerate skin wound healing. This study explored the effects of peptide Ser-Ile-Lys-Val-Ala-Val (SIKVAV)-modified chitosan hydrogels in skin wound healing. General observation demonstrated that SIKVAV-modified chitosan hydrogels promoted the contraction of skin wounds compared with the negative and positive controls. Masson's trichrome staining indicated that peptide-modified chitosan hydrogels accelerated the deposition of more collagen fibers in the skin wounds compared with the negative and positive controls. Immunohistochemistry assays showed that more myofibroblasts were deposited and more angiogenesis was found in skin wounds treated with peptide-modified chitosan hydrogels compared with the negative and positive controls. In addition, qRT-PCR assays showed that peptide-modified chitosan hydrogels promoted the expression of TGF-ß1 (transforming growth factor-ß1) mRNA and inhibited the expression of TNF-α (tumor necrosis factor-α) mRNA and IL-1ß (Interleukin-1ß) mRNA and IL-6 (Interleukin-6) mRNA in skin wounds. Taken together, these results indicate the potential of SIKVAV-modified chitosan hydrogels in skin wound healing as complex biomaterials.

Peptide-Modified Chitosan Hydrogels Accelerate Skin Wound Healing by Promoting Fibroblast Proliferation, Migration, and Secretion.

Skin wound healing is a complicated process that involves a variety of cells and cytokines. Fibroblasts play an important role in this process and participate in transformation into myofibroblasts, the synthesis of extracellular matrix (ECM) and fibers, and the secretion of a variety of growth factors. This study assessed the effects of peptide Ser-Ile-Lys-Val-Ala-Val (SIKVAV)--modified chitosan hydrogels on skin wound healing. We investigated the capability of peptide SIKVAV to promote cell proliferation and migration, the synthesis of collagen, and the secretion of a variety of growth factors using fibroblasts in vitro. We also treated skin wounds established in mice using peptide SIKVAV-modified chitosan hydrogels. Hematoxylin and eosin staining showed that peptide-modified chitosan hydrogels enhanced the reepithelialization of wounds compared with negative and positive controls. Masson's trichrome staining demonstrated that more collagen fibers were deposited in the wounds treated with peptide-modified chitosan hydrogels compared with the negative and positive controls. Immunohistochemistry revealed that the peptide-modified chitosan hydrogels promoted angiogenesis in the skin wound. Taken together, these results suggest that peptide SIKVAV-modified chitosan hydrogels may be useful in wound dressing and the treatment of skin wounds.

Peptide-modified chitosan hydrogels promote skin wound healing by enhancing wound angiogenesis and inhibiting inflammation.

Cutaneous wound healing following trauma is a complex and dynamic process involving multiple overlapping events following trauma. Two critical elements affecting skin wound healing are neovascularization and inflammation. A nascent vessel can provide nutrition and oxygen to a healing wound. Therefore, treatments strategies that enhance angiogenesis and inhibit inflammation can promote skin wound healing. Previous studies have shown that the SIKVAV peptide (Ser-Ile-Lys-Val-Ala-Val) from laminin can promote angiogenesis in vitro. This study evaluated the effects of peptide SIKVAV-modified chitosan hydrogels on skin wound healing. We established skin wounds established in mice and treated them with SIKVAV-modified chitosan hydrogels. H&E staining showed that peptide-modified chitosan hydrogels accelerated the reepithelialization of wounds compared with the negative and positive controls. Immunohistochemistry analysis demonstrated that more myofibroblasts were deposited at wounds treated with peptide-modified chitosan hydrogels that at those treated with negative and positive controls. In addition, peptide-modified chitosan hydrogels promoted angiogenesis as well as keratinocyte proliferation and differentiation, but inhibited inflammation in skin wounds. Taken together, these results suggest that SIKVAV-modified chitosan hydrogels are a promising treatment component for healing-impaired wounds.