Nanomedicine Laboratory, Center for Materials Science (CMS), Zewail City of Science and Technology, Giza 12578, Egypt.
Department of Chemistry, School of Sciences and Engineering, American University in Cairo, New Cairo 11835, Egypt.
ACS Appl Bio Mater. 2022 Aug 15;5(8):3678-3694. doi: 10.1021/acsabm.2c00147. Epub 2022 Jul 12.
We report the development and evaluation of a series of well-designed single-dose extracellular matrix (ECM)-mimicking nanofibers (NFs)-reinforced hydrogel (HG)-based skin substitute for wound healing. The HG matrix of the proposed skin substitute is composed of gelatin (GE) and sodium alginate (SA), and incorporates hyaluronic acid (HA) as a key component of the natural ECM, as well as the antimicrobial extract (PE). This HG nanocomposite was cross-linked by the biocompatible -(3-(dimethylamino)propyl)-'-ethylcarbodiimide hydrochloride (EDC) cross-linker, and was reinforced with fragmented -ferulic acid (FA)-loaded cellulose acetate/polycaprolactone (PCL/CA) NFs. The NFs were obtained via wet electrospinning into a poly(vinyl alcohol) (PVA) coagulating solution to closely resemble the porous structure of the ECM fibers, which facilitates cell migration, attachment, and proliferation. The proposed design of the skin substitute allows adjustable mechanical characteristics and outstanding physical properties (swelling and biodegradability), as well as an excellent porous microstructure. The developed skin substitutes were characterized using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and electron microscopy. In addition, the biodegradability, biocompatibility, bioactivity, mechanical, and in vitro drug release characteristics were investigated. Moreover, an in vivo excisional full-thickness defect model was conducted to assess skin regeneration and healing effectiveness. The average diameters of the plain and FA-loaded NFs are 210 ± 12 nm and 452 ± 25 nm, respectively. The developed ECM-mimicking skin substitutes demonstrated good antibacterial activity, free-radical scavenging activity, cytocompatibility, porosity, water absorption ability, and good biodegradability. In vivo application of the ECM-mimicking skin substitutes revealed their excellent wound-healing activity and their suitability for single-dose treatment of deep wounds with reducing the wound diameter to 0.95 mm after 15 days of treatment. Moreover, the histological investigation of the wound area demonstrated that the applied skin substitutes have not only enhanced the wound healing progress, but also can participate in improving the quality of the regenerated skin in the treated area via facilitating collagen fibers regeneration and deposition.
我们报告了一系列精心设计的基于细胞外基质（ECM）模拟纳米纤维（NF）增强水凝胶（HG）的单层皮肤替代物的开发和评估，用于伤口愈合。所提出的皮肤替代物的 HG 基质由明胶（GE）和海藻酸钠（SA）组成，并将透明质酸（HA）作为天然 ECM 的关键成分，以及抗菌提取物（PE）纳入其中。该 HG 纳米复合材料通过生物相容性的 -（3-（二甲基氨基）丙基）-'-乙基碳化二亚胺盐酸盐（EDC）交联剂交联，并通过碎片 -阿魏酸（FA）负载的醋酸纤维素/聚己内酯（PCL/CA）NF 增强。NF 通过湿静电纺丝到聚乙烯醇（PVA）凝固溶液中获得，以紧密模仿 ECM 纤维的多孔结构，从而促进细胞迁移、附着和增殖。所提出的皮肤替代物设计允许可调的机械特性和出色的物理特性（膨胀和生物降解性）以及出色的多孔微观结构。使用傅里叶变换红外（FTIR）光谱、差示扫描量热法（DSC）和电子显微镜对所开发的皮肤替代物进行了表征。此外，还研究了生物降解性、生物相容性、生物活性、机械性能和体外药物释放特性。此外，还进行了体内切除全厚度缺陷模型以评估皮肤再生和愈合效果。普通和 FA 负载 NF 的平均直径分别为 210 ± 12nm 和 452 ± 25nm。开发的 ECM 模拟皮肤替代物表现出良好的抗菌活性、自由基清除活性、细胞相容性、多孔性、吸水性和良好的生物降解性。ECM 模拟皮肤替代物的体内应用显示出其出色的伤口愈合活性，并且适合于单次剂量治疗深度伤口，在治疗 15 天后将伤口直径缩小至 0.95mm。此外，对伤口区域的组织学研究表明，应用的皮肤替代物不仅增强了伤口愈合的进展，而且还可以通过促进胶原蛋白纤维的再生和沉积，参与改善治疗区域再生皮肤的质量。
