Abstract This work deals with the design and manufacturing of porous gelatin-based hybrid materials with tuneable supramolecular structure and morphology for potential application as scaffolds in tissue engineering and drug delivery. The material manufacturing involves the following two steps: 1) sol–gel synthesis of hybrid gels by combining gelatin (either type A or type B) with 3-glycidoxypropyltrimethoxysilane (GOTMS) to promote the crosslinking of protein macromolecules through the formation of silsesquioxanes domains; 2) supercritical CO2 processing of hybrid gels to obtain porous materials. The obtained porous materials were characterized by means of NMR and FTIR spectroscopies to assess their chemical structure; SEM microscopy, low temperature N2 adsorption-desorption analysis and DSC/TGA characterizations were also used to evaluate morphology, textural properties and thermal behaviour, respectively. In vitro murine fibroblasts culture tests were carried out to assess the materials cytotoxicity. Finally, we reported herein a solution impregnation process combined with supercritical CO2 drying suitable to load the porous materials with 5-fluorouracil, a molecule widely used for cancer therapy. The release of 5-fluorouracil from the porous materials was evaluated in vitro in both gastric and plasmatic conditions. The chemico-physical results confirm the crosslinking of gelatin-based structure due to the reaction between the amino-groups of gelatins with epoxy groups of GOTMS and the formation of silsesquioxanes nano-domains. Most interesting, the chemical structure and porosity at both nano- and micro-scale were strongly dependent on gelatin source and GOMTS concentration used. The porous materials are not cytotoxic and may be loaded with 5-fluorouracil, in presence of two different solvents, for biomedical purposes. In particular, drug loading, in the 5-15 wt% range, and drug delivery depended on protein source and solvent used during the drug loading.

中文翻译：

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具有可调多尺度形态的混合明胶多孔材料，用于组织工程和药物递送

摘要 这项工作涉及具有可调超分子结构和形态的多孔明胶基杂化材料的设计和制造，以作为组织工程和药物递送中的支架的潜在应用。材料制造包括以下两个步骤：1）通过将明胶（A 型或 B 型）与 3-缩水甘油氧基丙基三甲氧基硅烷 (GOTMS) 结合以通过形成倍半硅氧烷结构域促进蛋白质大分子的交联，溶胶-凝胶合成混合凝胶；2) 混合凝胶的超临界 CO2 处理以获得多孔材料。通过NMR和FTIR光谱对所得多孔材料进行表征以评估其化学结构；扫描电镜，低温 N2 吸附-解吸分析和 DSC/TGA 表征也分别用于评估形态、结构特性和热行为。进行体外鼠成纤维细胞培养试验以评估材料的细胞毒性。最后，我们在本文中报道了一种溶液浸渍工艺与超临界 CO2 干燥相结合，适合将 5-氟尿嘧啶（一种广泛用于癌症治疗的分子）加载到多孔材料中。在体外胃和血浆条件下评估了多孔材料中 5-氟尿嘧啶的释放。化学物理结果证实了明胶基结构的交联，这是由于明胶的氨基与 GOTMS 的环氧基之间的反应以及倍半硅氧烷纳米域的形成。最有趣的，纳米级和微米级的化学结构和孔隙率强烈依赖于明胶来源和所使用的 GOMTS 浓度。多孔材料没有细胞毒性，可以在两种不同溶剂的存在下装载 5-氟尿嘧啶，用于生物医学目的。特别是，在 5-15 wt% 范围内的载药量和药物递送取决于载药过程中使用的蛋白质来源和溶剂。