title: Interactions between structural and chemical biomimetism in synthetic stem cell niches.
abstract: Advancements in understanding stem cell functions and differentiation are of key importance for the clinical success of stem-cell-based therapies. 3D structural niches fabricated by two-photon polymerization are a powerful platform for controlling stem cell growth and differentiation. In this paper, we investigate the possibility of further controlling stem cell fate by tuning the mechanical properties of such niches through coating with thin layers of biomimetic hyaluronan-based and gelatin-based hydrogels. We first assess the biocompatibility of chemical coatings and then study the interactions between structural and chemical biomimetism on the response of MSCs in terms of proliferation and differentiation. We observed a clear effect of the hydrogel coating on otherwise identical 3D scaffolds. In particular, in gelatin-coated niches we observed a stronger metabolic activity and commitment toward the osteo-chondral lineage with respect to hyaluronan-coated niches. Conversely, a reduction in the homing effect was observed in all the coated niches, especially in gelatin-coated niches. This study demonstrates the feasibility of controlling independently different mechanical cues, in bioengineered stem cell niches, i.e. the 3D scaffold geometry and the surface stiffness. This will allow, on the one hand, understanding their specific role in stem cell proliferation and differentiation and, on the other hand, finely tuning their synergistic effect.
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering 'Giulio Natta', Politecnico di Milano, 32, piazza Leonardo da Vinci, 20133, Milano, Italy.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Nava
authors.forename: Manuela T
authors.initials: MT
authors.lastname: Raimondi
authors.forename: Caterina
authors.initials: C
authors.lastname: Credi
authors.forename: Carmela
authors.initials: C
authors.lastname: De Marco
authors.forename: Stefano
authors.initials: S
authors.lastname: Turri
authors.forename: Giulio
authors.initials: G
authors.lastname: Cerullo
authors.forename: Roberto
authors.initials: R
authors.lastname: Osellame
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology; D004852:Epoxy Compounds / Q000737:chemistry; D005434:Flow Cytometry; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry; D021621:Imaging, Three-Dimensional; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008689:Methacrylates / Q000737:chemistry; D044085:Microfluidics; D010011:Osteocytes / Q000166:cytology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D055153:Stem Cell Niche / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D004852:Epoxy Compounds; D020100:Hydrogels; D008689:Methacrylates; D005780:Gelatin; D006820:Hyaluronic Acid; C007870:glycidyl methacrylate