# Poly(vinyl alcohol)/Gelatin Scaffolds Allow Regeneration of Nasal Tissues
###### Abstract
Some studies have proposed biocompatible scaffolds based on decellularized cartilage, collagen, polycaprolactone (PCL), poly(L-lactic) acid (PLLA), poly (lactic-co-glycol) acid (PLGA) [19, 20, 21, 22], and stem cells, such as mesenchymal stromal cells (MSCs), easy to isolate and already used in clinical procedures, or septal chondrocytes [23, 24, 25]. Injectable fibrin scaffolds containing septal chondrocytes have been applied directly into the damaged site [26], and constructs fabricated by 3D printing, with the desired shapes, have also been developed [27]. Although these studies gave rise to interesting results in vitro, in animals and recently also in humans, currently no TE construct has been proposed that is able to regenerate all the anatomical structures of the nose [28]. With the aim of further investigating in this field, several materials different from those tested so far could be tested. In this regard, polyvinyl alcohol (PVA) represents a valuable candidate due to its compatibility with many cells and tissues, non-toxicity and non-tumorigenicity, along with its hydrogel-forming capability, which leads to high water contents, similar to that of natural cartilage [29]. In our recent studies, we showed that PVA-based sponges retain some key features of PVA hydrogels, being also able to widely modulate pore size to accomplish different cells and tissue structures [30], thus becoming an interesting scaffold also in the otolaryngological field. By virtue of its hydrophilic nature, PVA can be easily blended with several biomolecules [31]. PVA/gelatin (G) sponges, with highly interconnected pores, allow a good diffusion of nutrients and a high cell penetration. MSCs have demonstrated to differentiate into chondrocytes producing typical molecules of the cartilage extracellular matrix (ECM), both using traditional or scaffold-mediated culture methods [32,33]. These constructs subjected to mechanical stimulation in a bioreactor were also able to generate cartilage with elastic fibers, important for the reconstruction of the auric [34]. Finally, PVA/G sponges seeded with both bone marrow MSCs, differentiated into osteogenic lineage, and human umbilical vein endothelial cells (hUVECs), terminally differentiated towards endothelial lineage, showed first evidence of vascularized bone generation. This is important, in perspective, to improve implant viability during the regenerative process in vivo [35]. MSCs can differentiate into all mesodermal tissues; however, an efficient differentiation into the endothelial phenotype is still a subject of investigation [36]. The mesodermal (or mesangiogenic) progenitor cells (MPCs) are bone marrow precursors of the MSCs, which, being a step upstream in the mesengenic process, still have a strong potency for vasculogenesis [37; 38]. Having a single cellular source to generate the most important structural tissues of the nose, including, but not limited to cartilage, bone, and vasculature, could definitively offer improved therapeutic solutions. Fibrocartilage is a tissue rich in type I collagen fibers, containing few chondrocytes; the fibers are organized in very dense bundles that make the fabric highly resistant to compression. It is a transition tissue between hyal cartilage and dense connective tissue, typical of ligaments, also determinant for holding the nasal structures together and anchoring them to the face bones [39]. The aim of this study was to create a simple platform of three-dimensional (3D) cell/scaffold constructs for the regeneration of different nasal tissues by a single scaffold, the PVA/G sponge, and a single source of patient's cells, the MPCs, able to generate different cell progenies: chondrogenic, osteogenic, endothelial and fibrobl. We thus focused on the achievement of 3D constructs allowing the regeneration of hyaline cartilage, vascularized bone and fibrocartilage, which are the main connective tissues in the nose.