Highly Porous Gelatin Reinforced 3D Scaffolds for Articular Cartilage Regeneration Sofia Amadori, Paola Torricelli, Silvia Panzavolta,* Annapaola Parrilli, Milena Fini, Adriana Bigi 3D highly porous (93% total porosity) gelatin scaffolds were prepared according to a novel, simple method, which implies gelatin foaming, gelification, soaking into ethanol and successive freeze- drying. Reinforcement of the as-prepared scaffolds (GEL) was performed through immersion in aqueous solutions at different gelatin concentrations. Reinforcement solutions with and without genipin addition allowed to prepare two series of samples:cross-linked and uncross-linked samples, respectively. The amount of gelatin adsorbed onto the reinforced samples increases as a function of gelatin concentration in solution and provokes a drastic improvement of the compressive modulus and collapse strength up to values of about 30 and 4 MPa, respectively. The open and interconnected porosity, although slightly reduced, is still of the order of 80% in the samples reinforced with the highest concentration of gelatin. Water uptake ability evaluated after immer- sion in PBS for 20 s decreases with gelatin reinforce- ment. The presence of genipin in cross-linked samples reduces gelatin release and stabilizes the scaffolds in solution. Chondrocytes from human articular carti- lage adhere, proliferate, and penetrate into the scaffolds. The evaluation of differentiation markers both on the supernatants of cell culture and by means of quantitative polymerase chain reaction (qPCR) indicates a dose-dependent promotion of cell differ- entiation. 1. Introduction Regenerative medicine needs advanced materials with hierarchical 3D architectures, able to provide a friendly interaction with biological tissues and promote tissue repair. The scaffolds should be designed properly in order to offer a suitable surface chemistry for cell attachment, proliferation, and differentiation, and, once implanted, they must support the tissue regeneration process. To this aim, key parameters are porosity, pore size, and inter- connectivity, which must allow cellular migration, as well as nutrient and waste exchange. [1] S. Amadori, S. Panzavolta, A. Bigi Department of Chemistry ‘‘G. Ciamician’’, University of Bologna, via Selmi 2, 40126 Bologna, Italy E-mail: silvia.panzavolta@unibo.it Fax: þ39 051 2099456 P. Torricelli, A. Parrilli, M. Fini Laboratory of Preclinical and Surgical Studies, Research Institute Codivilla Putti – Rizzoli Orthopaedic Institute, via di Barbiano, 40126 Bologna, Italy Full Paper ß 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Macromol. Biosci. 2015, DOI: 10.1002/mabi.201500014 1 wileyonlinelibrary.com Early View Publication; these are NOT the final page numbers, use DOI for citation !! R