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Preclinical efficacy study of a porous biopolymeric scaffold based on gelatin-hyaluronic acid-chondroitin sulfate in a porcine burn injury model: role of critical molecular markers (VEGFA, N-cadherin, COX-2), gamma sterilization efficacy and a comparison of healing potential to Integra™
Biomedical Materials ( IF 4 ) Pub Date : 2021-09-01 , DOI: 10.1088/1748-605x/ac1d3e
Amit Khurana 1, 2, 3 , Anil Kumar Banothu 2, 4 , A V Thanusha 1 , Aradhana Nayal 1 , Amit Kumar Dinda 5 , Maneesh Singhal 6 , Kala Kumar Bharani 2, 3, 4 , Veena Koul 1
Affiliation  

Development of scaffold from biopolymers can ease the requirements for donor skin autograft and plays an effective role in the treatment of burn wounds. In the current study, a porous foam based, bilayered hydrogel scaffold was developed using gelatin, hyaluronic acid and chondroitin sulfate (G-HA-CS). The fabricated scaffold was characterized physicochemically for pre- and post-sterilization efficacy by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). In-vitro studies proved that the scaffold promoted cellular proliferation. The efficacy of G-HA-CS scaffold was compared with Integra™ at different time points (7, 14, 21 and 42 days), in a swine second degree burn wound model. Remarkable healing potential of the scaffold was evident from the wound contraction rate, reduction of IL-6, TNF-α and C3. The expression of healing markers TGF-β1 and collagen 1 revealed significant skin regeneration with regulated fibroblast activation towards the late phase of healing (p < 0.001 at day 21 and 42 vs. control). Expression of Vascular Endothelial Growth Factor A (VEGFA), vimentin and N-cadherin were found to favor angiogenesis and skin regeneration. Mechanistically, scaffold promoted wound healing by modulation of CD-45, cyclooxygenase-2 and MMP-2. Thus, the promising results with foam based scaffold, comparable to Integra™ in swine burn injury model offer an innovative lead for clinical translation for effective management of burn wound.



中文翻译:

基于明胶-透明质酸-硫酸软骨素的多孔生物聚合物支架在猪烧伤模型中的临床前功效研究:关键分子标志物(VEGFA、N-钙粘蛋白、COX-2)的作用、伽马灭菌功效和愈合潜力的比较到 Integra™

用生物聚合物开发支架可以缓解供体皮肤自体移植的需求,并在烧伤创面的治疗中发挥有效作用。在目前的研究中,使用明胶、透明质酸和硫酸软骨素 (G-HA-CS) 开发了一种基于多孔泡沫的双层水凝胶支架。通过扫描电子显微镜 (SEM)、傅里叶变换红外 (FTIR) 光谱、差示扫描量热法 (DSC) 和热重分析 (TGA) 对制造的支架进行物理化学表征,以了解灭菌前和灭菌后的功效。体外研究证明,支架促进细胞增殖。在猪二级烧伤创面模型中,在不同时间点(7、14、21 和 42 天)比较了 G-HA-CS 支架与 Integra™ 的功效。从伤口收缩率、IL-6、TNF- α和C3的减少可以看出支架具有显着的愈合潜力。愈合标志物 TGF- β1和胶原蛋白 1 的表达揭示了显着的皮肤再生,并在愈合后期调节成纤维细胞活化(p在第 21 天和第 42 天与对照相比 < 0.001)。发现血管内皮生长因子 A (VEGFA)、波形蛋白和 N-钙粘蛋白的表达有利于血管生成和皮肤再生。从机制上讲,支架通过调节 CD-45、环氧合酶 2 和 MMP-2 促进伤口愈合。因此,与猪烧伤模型中的 Integra™ 相媲美的基于泡沫的支架的有希望的结果为临床转化以有效管理烧伤伤口提供了创新的先导。

更新日期:2021-09-01
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