Chitosan/Sodium Alginate/Velvet Antler Blood Peptides Hydrogel Promotes Diabetic Wound Healing via Regulating Angiogenesis, Inflammatory Response and Skin Flora

Abstract

Background Diabetic ulcer remains a clinical challenge due to impaired angiogenesis and persistent inflammation, requiring new alternative therapies to promote tissue regeneration. Purpose In this study, chitosan/sodium alginate/velvet antler blood peptides (CS/SA/VBPs) hydrogel (CAVBPH) was fabricated and used in the treatment of skin wounds in type 2 diabetes mellitus (T2D) for the first time. Methods VBPs were prepared by hydrolysis and ultrafiltration, and their sequences were identified using LC-MS/MS. The CAVBPH was further fabricated and characterized. A mouse model of T2D was induced by a high-sugar and high-fat diet (HSFD) and streptozotocin (STZ) injection. CAVBPH was applied topically to T2D wounds, and its effects on skin repair and potential biological mechanisms were analyzed by appearance observation, histopathological staining, bioinformatics analysis, Western blot, and 16S rRNA sequencing. Results VBPs had numerous short-chain active peptides, excellent antioxidant activity, and a low hemolysis rate. CAVBPH exhibited desirable biochemical properties and participated in the diabetic wound healing process by promoting cell proliferation (PCNA and α-SMA) and angiogenesis (capillaries and CD31) and alleviating inflammation (CD68). Mechanistically, the therapeutic effect of CAVBPH on chronic wounds might rely on activating the PI3K/AKT/mTOR/HIF-1α/VEGFA pathway and reversing the expression of inflammatory cytokines TNF-α and IL-1β. The results of 16S rRNA sequencing indicated that T2D significantly altered the diversity and structure of skin flora at the wound site. CAVBPH treatment elevated the relative abundance of beneficial microbes (e.g., Corynebacterium_1 and Lactobacillus ) and reversed the structural imbalance of skin microbiota. Conclusion These results indicate that CAVBPH is a promising wound dressing, and its repair effect on diabetic wounds by regulating angiogenesis, inflammatory response, and skin flora may depend on the rich small peptides in VBPs.

Promotion of non-small cell lung cancer tumor growth by FHL2 via inducing angiogenesis and vascular permeability

“…VEGFA regulates vascular permeability by activating VEGFR2, which is followed by the activation of AKT-mTOR signaling ( 21 , 23 ). Thus, we examined whether VEGFR2-AKT-mTOR signaling pathway is involved in FHL2 -induced vascular leakiness.…”

Advanced multifunctional hydrogels for diabetic foot ulcer healing: Active substances and biological functions

“…The amphiphilic peptide A 9 K 2 associates with cell membrane and kills bacteria by membrane permeabilization. In addition to bactericidal effect, some hydrogels can improve the relative abundance of beneficial skin microbiota and reverse the structural imbalance of microbiota 95 . To sum up, self‐antibacterial hydrogels are demonstrated to be a promising dressing to maintain the long‐lasting antibacterial efficacy without toxicity.…”

Chitosan-Based Biomaterials for Tissue Regeneration

“…Chitosan derivatives can effectively interact with cellular signaling pathways and the compounds mentioned above, which are involved in the immune system’s inflammatory response to skin damage. For instance, the study by Hao and colleagues revealed that a chitosan/sodium alginate/velvet antler blood peptides hydrogel reduced acute inflammatory response mainly via the activation of PI3K/AKT/mTOR/HIF-1α/VEGFA pathway and suppression of TNF-α and IL-1β expression [ 104 ]. Both of these factors play an essential role in activating immune response and initiation of inflammation.…”

“…Moreover, chitosan can affect the expression of various cell surface markers. During its activity, the chitosan hydrogels can greatly decrease markers expressed mainly by macrophages and monocytes, such as CD68, during the inflammatory phase of the immune response and increase the expression of the endothelial cell surface markers such as CD31, indicative of increased angiogenesis [ 97 , 104 ]. Aside from its hemostatic properties, the chitosan hydrogel demonstrated antibacterial activity against Methicillin-resistant Staphylococcus aureus.…”