*Article* **Biomimetic and Bioactive Small Diameter Tubular Scaffolds for Vascular Tissue Engineering**

**Elisabetta Rosellini \* , Niccoletta Barbani, Luigi Lazzeri and Maria Grazia Cascone**

Department of Civil and Industrial Engineering, University of Pisa, Largo Lucio Lazzarino, 56122 Pisa, Italy

**\*** Correspondence: elisabetta.rosellini@unipi.it; Tel.: +39-050-2217908

**Abstract:** The present work aimed at the production and characterization of small caliber biomimetic and bioactive tubular scaffolds, which are able to favor the endothelialization process, and therefore potentially be suitable for vascular tissue engineering. The tubular scaffolds were produced using a specially designed mold, starting from a gelatin/gellan/elastin (GGE) blend, selected to mimic the composition of the extracellular matrix of native blood vessels. GGE scaffolds were obtained through freeze-drying and subsequent cross-linking. To obtain systems capable of promoting endothelization, the scaffolds were functionalized using two different bioactive peptides, Gly-Arg-Gly-Asp-Ser-Pro (GRGSDP) and Arg-Glu-Asp-Val (REDV). A complete physicochemical, mechanical, functional, and biological characterization of the developed scaffolds was performed. GGE scaffolds showed a good porosity, which could promote cell infiltration and proliferation and a dense external surface, which could avoid bleeding. Moreover, developed scaffolds showed good hydrophilicity, an elastic behavior similar to natural vessels, suitability for sterilization by an ISO accepted treatment, and an adequate suture retention strength. In vitro cell culture tests showed no cytotoxic activity against 3T3 fibroblasts. The functionalization with the REDV peptide favored the adhesion and growth of endothelial cells, while GRGDSP-modified scaffolds represented a better substrate for fibroblasts.

**Keywords:** gelatin; gellan; elastin; endothelialization; functionalization; peptide
