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Objective(s): The skin serves as the main defense barrier, protecting against injuries, and preventing infection and water loss. Consequently, wound healing and skin regeneration are crucial aspects of wound management. A novel hydrogel scaffold was developed by incorporating carboxymethyl cellulose (CMC) and gelatin (Gel) hydrogels cross-linked with 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (EDC) containing Sphingosine 1-phosphate (S1P). This hydrogel is applied topically to treat acute wounds and is covered with a human acellular amniotic membrane (hAAM) as a secondary dressing. Materials and Methods: The scaffold was subjected to in vitro cell viability, red blood cell hemolysis, blood clotting index, and in vivo assays. Real-time PCR was implemented to verify the expression of genes involved in skin wounds. The physical and chemical properties of the scaffolds were also tested using weight loss, swelling ratio, scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and mechanical tensile analysis. Results: The synthetic scaffold is biocompatible as evidenced by the high percentage of 3T3 cell viability (127%) after 72 hr. Additionally, excellent hemocompatibility with a low hemolytic effect (2.26%) was observed. Our in vivo wound healing assay demonstrated that CMC/Gel/S1P/hAAM wound dressing led to faster wound healing in treated rats compared to the control group over 14. Also, the mechanical tests showed that the amniotic membrane and the hAAM had very different Young’s modulus and elongation at break values. Conclusion: This study demonstrates the effectiveness of the CMC/Gel/EDC hydrogel with S1P as a wound dressing. Additionally, hAAM exhibits excellent characteristics as a protective layer for the treatment of acute wounds. [ABSTRACT FROM AUTHOR]

Skin tissue engineering has become an increasingly popular alternative to conventional treatments for skin injuries. Hydrogels, owing to their advantages have become the ideal option for wound dressing, and they are extensively employed in a mixture of different drugs to accelerate wound healing. Sodium alginate is a readily available natural polymer with advantages such as bio-compatibility and a non-toxicological nature that is commonly used in hydrogel form for medical applications such as wound repair and drug delivery in skin regenerative medicine. Losartan is a medicine called angiotensin receptor blocker (ARB) that can prevent fibrosis by inhibiting AT1R (angiotensin II type 1 receptor). In this research, for the first time, three-dimensional scaffolds based on cross-linked alginate hydrogel with CaCl2 containing different concentrations of losartan for slow drug release and exudate absorption were prepared and characterized as wound dressing. Alginate hydrogel was mixed with 10, 1, 0.1, and 0.01 mg/mL of losartan, and their properties such as morphology, chemical structure, water uptake properties, biodegradability, stability assay, rheology, blood compatibility, and cellular response were evaluated. In addition, the therapeutic efficiency of the developed hydrogels was then assessed in an in vitro wound healing model and with a gene expression. The results revealed that the hydrogel produced was very porous (porosity of 47.37 ± 3.76 µm) with interconnected pores and biodegradable (weight loss percentage of 60.93 ± 4.51% over 14 days). All hydrogel formulations have stability under various conditions. The use of CaCl2 as a cross-linker led to an increase in the viscosity of alginate hydrogels. An in vitro cell growth study revealed that no cytotoxicity was observed at the suggested dosage of the hydrogel. Increases in Losartan dosage, however, caused hemolysis. In vivo study in adult male rats with a full-thickness model showed greater than 80% improvement of the primary wound region after 2 weeks of treatment with alginate hydrogel containing 0.1 mg/mL Losartan. RT-PCR and immunohistochemistry analysis showed a decrease in expression level of TGF-β1 and VEGF in treatment groups. Histological analysis demonstrated that the alginate hydrogel containing Losartan can be effective in wound repair by decreasing the size of the scar and tissue remodeling, as evidenced by future in vivo studies. [ABSTRACT FROM AUTHOR]

Hydrogels are biomolecules made of artificial and natural polymers. Their quasi-three-dimensional structure has created unique features. They are very hydrophilic, and in addition to the high inflation rate, they also have excellent water maintenance capacity, biodegradability, biocompatibility, and strong mechanical properties. These properties are used in many tissue engineering applications. All these features have made these scaffolds widely used as attractive structures in the world of tissue engineering and regeneration medicine. In addition to research, scaffolds entered the field of medicine and are expected to play a significant role in the repair of many tissues in the future. This study aims to review the various polymers involved in hydrogel fabrication and their application in the repair of diverse tissues and clinical trials., Competing Interests: The authors declare no conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 The Author(s).)