Control of angiogenesis and host response by modulating the cell adhesion properties of an Elastin-Like Recombinamer-based hydrogel

• Published in: Biomaterials 2017-08, Vol.135, p.30-41
• Main Authors: Staubli, Sebastian, Cerino, Giulia, De Torre, Israel Gonzalez, Alonso, Matilde, Oertli, Daniel, Eckstein, Friedrich, Glatz, Katharina, Rodríguez Cabello, José Carlos, PhD, Marsano, Anna, PhD
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Angiogenesis; Animals; Cell Adhesion - physiology; Cell Culture Techniques; Dentistry; Elastin - chemistry; Elastin-Like Recombinamers; Flow Cytometry; Functionalization; Host reaction; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; In Situ Hybridization; Male; Mesenchymal Stromal Cells - cytology; Microscopy, Electron, Scanning; Neovascularization, Physiologic - physiology; Rats; Stromal Cells - cytology; Stromal vascular fraction
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2017.04.047

Abstract The control of the in vivo vascularization of engineered tissue substitutes is essential in order to obtain either a rapid induction or a complete inhibition of the process (e.g. in muscles and hyaline-cartilage, respectively). Among the several polymers available, Elastin-Like Recombinamers (ELRs)-based hydrogel stands out as a promising material for tissue engineering thanks to its viscoelastic properties, non-toxicity, and non-immunogenicity. In this study, we hypothesized that varying the cell adhesion properties of ELRs-hydrogels could modulate the high angiogenic potential of adipose tissue-derived stromal vascular fraction (SVF) cells, predominantly composed of endothelial/mural and mesenchymal cells. Human SVF cells, embedded in RGD-REDV-bioactivated or unmodified ELRs-hydrogels, were implanted in rat subcutaneous pockets either immediately or upon 5-day-culture in perfusion-bioreactors. Perfusion-based culture enhanced the endothelial cell cord-like-organization and the release of pro-angiogenic factors in functionalized constructs. While in vivo vascularization and host cell infiltration within the bioactivated gels were highly enhanced, the two processes were strongly inhibited in non-functionalized SVF-based hydrogels up to 28 days. ELRs-based hydrogels showed a great potential to determine the successful integration of engineered substitutes thanks to their capacity to finely control the angiogenic/inflammation process at the recipient site, even in presence of SVF cells.