Hybrid gelatin-based porous materials with a tunable multiscale morphology for tissue engineering and drug delivery

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 CO 2 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 N 2 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 CO 2 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 sour ce 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.