title: Thick soft tissue reconstruction on highly perfusive biodegradable scaffolds.
abstract: The lack of a vascular network and poor perfusion is what mostly prevents three-dimensional (3D) scaffolds from being used in organ repair when reconstruction of thick tissues is needed. Highly-porous scaffolds made of poly(L-lactic acid) (PLLA) are prepared by directional thermally induced phase separation (dTIPS) starting from 1,4-dioxane/PLLA solutions. The influence of polymer concentration and temperature gradient, in terms of imposed intensity and direction, on pore size and distribution is studied by comparison with scaffolds prepared by isotropic TIPS. The processing parameters are optimized to achieve an overall porosity for the 3D scaffolds of about 93% with a degree of interconnectivity of 91%. The resulting pore network is characterized by the ordered repetition of closely packed dendrite-like cavities, each one showing stacks of 20 microm large side lamellar branches departing from 70 microm diameter vertical backbones, strongly resembling the vascular patterns. The in vitro biological responses after 1 and 2 weeks are evaluated from mesenchymal (bone marrow stromal) cells (MSC) static culturing. A novel vacuum-based deep-seeding method is set up to improve uniform cell penetration down to scaffold thicknesses of over 1 mm. Biological screenings show significant 3D scaffold colonization even after 18 h, while cellular retention is observed up to 14 d in vitro (DIV). Pore architecture-driven cellular growth is accompanied by cell tendency to preserve their multi-potency towards differentiation. Confluent tissues as thick as 1 mm were reconstructed taking advantage of the large perfusion enhanced by the highly porous microstructure of the engineered scaffolds, which could successfully serve for applications aimed at vascular nets and angiogenesis.
authors.affiliation: NAST Center & Dipartimento di Scienze e Tecnologie Chimiche, University of Rome Tor Vergata, 00133 Roma, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Mandoli
authors.forename: Barbara
authors.initials: B
authors.lastname: Mecheri
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Forte
authors.forename: Francesca
authors.initials: F
authors.lastname: Pagliari
authors.forename: Stefania
authors.initials: S
authors.lastname: Pagliari
authors.forename: Felicia
authors.initials: F
authors.lastname: Carotenuto
authors.forename: Roberta
authors.initials: R
authors.lastname: Fiaccavento
authors.forename: Antonio
authors.initials: A
authors.lastname: Rinaldi
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Nardo
authors.forename: Silvia
authors.initials: S
authors.lastname: Licoccia
authors.forename: Enrico
authors.initials: E
authors.lastname: Traversa
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D010477:Perfusion; D016062:Porosity / Q000187:drug effects; D015203:Reproducibility of Results; D013696:Temperature; D013718:Tensile Strength / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials