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Giannoni P.,Centro Biotecnologie Avanzate CBA | Lazzarini E.,Centro Biotecnologie Avanzate CBA | Lazzarini E.,University of Genoa | Ceseracciu L.,Italian Institute of Technology | And 5 more authors.
Journal of Tissue Engineering and Regenerative Medicine | Year: 2015

Treatment of full-thickness cartilage defects relies on osteochondral bilayer grafts, which mimic the microenvironment and structure of the two affected tissues: articular cartilage and subchondral bone. However, the integrity and stability of the grafts are hampered by the presence of a weak interphase, generated by the layering processes of scaffold manufacturing. We describe here the design and development of a bilayer monolithic osteochondral graft, avoiding delamination of the two distinct layers but preserving the cues for selective generation of cartilage and bone. A highly porous polycaprolactone-based graft was obtained by combining solvent casting/particulate leaching techniques. Pore structure and interconnections were designed to favour in vivo vascularization only at the bony layer. Hydroxyapatite granules were added as bioactive signals at the site of bone regeneration. Unconfined compressive tests displayed optimal elastic properties and low residual deformation of the graft after unloading (< 3%). The structural integrity of the graft was successfully validated by tension fracture tests, revealing high resistance to delamination, since fractures were never displayed at the interface of the layers (n=8). Ectopic implantation of grafts in nude mice, after seeding with bovine trabecular bone-derived mesenchymal stem cells and bovine articular chondrocytes, resulted in thick areas of mature bone surrounding ceramic granules within the bony layer, and a cartilaginous alcianophilic matrix in the chondral layer. Vascularization was mostly observed in the bony layer, with a statistically significant higher blood vessel density and mean area. Thus, the easily generated osteochondral scaffolds, since they are mechanically and biologically functional, are suitable for tissue-engineering applications for cartilage repair. © 2015 John Wiley & Sons, Ltd.

Pennesi G.,MultiMedica IRCCS | Scaglione S.,Centro Biotecnologie Avanzate CBA | Scaglione S.,University of Genoa | Giannoni P.,Centro Biotecnologie Avanzate CBA | Quarto R.,University of Genoa
Current Pharmaceutical Biotechnology | Year: 2011

A stem cell is defined as a cell able to self-renew and at the same time to generate one or more specialized progenies. In the adult organism, stem cells need a specific microenvironment where to reside. This tissue-specific instructive microenvironment, hosting stem cells and governing their fate, is composed of extracellular matrix and soluble molecules. Cell-matrix and cell-cell interactions also contribute to the specifications of this milieu, regarded as a whole unitary system and referred to as "niche". For many stem cell systems a niche has been identified, but only partially defined. In regenerative medicine and tissue engineering, biomaterials are used to deliver stem cells in specific anatomical sites where a regenerative process is needed. In this context, biomaterials have to provide informative microenvironments mimicking a physiological niche. Stem cells may read and decode any biomaterial and modify their behavior and fate accordingly. Any material is therefore informative in the sense that its intrinsic nature and structure will anyway transmit a signal that will have to be decoded by colonizing cells. We still know very little of how to create local microenvironments, or artificial niches, that will govern stem cells behavior and their terminal fate. Here we will review some characteristics identifying specific niches and some of the requirements allowing stem cells differentiation processes. We will discuss on those biomaterials that are being projected/engineered/manufactured to gain the informative status necessary to drive proper molecular cross-talk and cell differentiation; specific examples will be proposed for bone and cartilage substitutes. © 2011 Bentham Science Publishers Ltd.

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