Chitosan/Sodium Alginate/Velvet Antler Blood Peptides Hydrogel Promoted Wound Healing by Regulating PI3K/AKT/mTOR and SIRT1/NF-κB Pathways

Abstract

Skin wound healing is a principal clinical challenge, and it is necessary to develop effective alternative treatments. Excessive inflammatory response is linked to delayed healing. This study was the first to report a multi-functional chitosan/sodium alginate/velvet antler blood peptides (VBPs) hydrogel (CAVBPH) and explore its potential mechanism to promote wound healing. The results showed that CAVBPH possessed desirable characteristics including thermo-sensitivity, antioxidation, antibacterial activity, biosafety, VBPs release behavior, etc., and significantly accelerated skin wound healing in mice. Specifically, the CAVBPH treatment enhanced cell proliferation, angiogenesis, and extracellular matrix (ECM) secretion, and also relieved inflammation at the wound site compared to the PBS-treated group and blank hydrogel scaffold-treated group. Mechanistically, the efficacy of CAVBPH might be related to the activation of the PI3K/AKT/mTOR and SIRT1/NF-κB pathways. Overall, CAVBPH seems to be a promising therapy for skin repair, probably relying on the abundant short-chain peptides in VBPs.

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

“…46 CS-based wound dressings have been shown to exert therapeutic effects by activating the PI3K/AKT pathway. 25,47 Interestingly, this work confirmed that CAVBPH more prominently exerted a pro-angiogenic effect than CAH via activating the PI3K/AKT/mTOR/HIF-1α/VEGFA pathway (Figure 7).…”

“…Previously, CS/SA polymer was shown to be more efficient in promoting wound repair than either CS or SA alone, and CS/SA composite hydrogel possessed excellent physicochemical properties to support it as a promising wound dressing scaffold. 25,42 The results of in vitro evaluation showed that CAVBPH possessed good porous breathability, swelling, biodegradability, antioxidant property, biocompatibility, biosafety, and release behavior of VBPs (Figures 1 and 2). Subsequently, we topically applied CAVBPH to the wound surface, on the one hand, to avoid direct contact of the wound with the outside, and on the other hand to continuously provide VBPs for wound healing.…”

“…VBPs were prepared using in vitro simulated gastrointestinal digestion and ultrafiltration technique as previously reported. 25 Peptide sequences were identified and analyzed by utilizing the Ultimate 3000 high-performance liquid chromatography system (HPLC, Thermo Fisher Scientific, USA) coupled with a Q Exactive™ Hybrid Quadrupole-Orbitrap™ Mass Spectrometer (Thermo Fisher Scientific, USA) with an ESI nanospray source.…”

“…Western blot analysis was performed for antibodies p-PI3K (#4228, Cell Signaling, China), PI3K (67071-1-lg, Proteintech, China), p-AKT (ARG51559, Arigobio, China), AKT (60203-2-lg, Proteintech, China), p-mTOR (ARG40666, Arigobio, China), mTOR (10745-1-AP, Proteintech, China), HIF-1α (20960-1-AP, Proteintech, China), VEGFA (19003-1-AP, Proteintech, China), IL-1β (26048-1-AP, Proteintech, China), TNF-α (17590-1-AP, Proteintech, China) and β-actin (66009-1-lg, Proteintech, China) as previously reported. 25 β-actin was used as an internal standard. The protein blots were visualized by enhanced chemiluminescent assay and quantified using the Image J software.…”

Type-A Gelatin-Based Hydrogel Infiltration and Degradation in Titanium Foams as a Potential Method for Localised Drug Delivery

“…In particular, the suppression of the NF-κB pathway is considered a promising therapeutic approach for regenerative medicine. In these senses, numerous systems based on hydrogels have been successfully developed for targeting mtROS and inhibiting of NF-κB activity for regenerative medicine [ 29 , 30 , 31 ]. In addition, the abovementioned drugs (antibiotics, NSADs, growth factors, and morphogens) can be included directly in the hydrogel.…”