Bioinspired scaffolds for bone and neural tissue and interface engineering

Abstract During the last decade, significant progress has been made in scaffold design for bone and nerve regeneration. The manipulation of material chemistry and processing technologies allows for improvement of structural and functional properties of tailor-made devices by the assembly of various materials combination or the ex novo synthesis of new materials with new functionalities (i.e., optical, electrical, magnetic), thus opening new and interesting routes for their application in tissue engineering. For instance, the manipulation of different materials may actively contribute to the design of highly complex platforms able to reproduce interface tissues such as meniscus, cartilage, and intervertebral disc, which also requires the re-invention/adaptation of conventional processing techniques for the fabrication of multilayered systems with chemical/physical gradients and multiple functionalities. Hence, it is mandatory to begin with a base of solid knowledge about material properties to properly design tailored scaffolds in order to optimize, case by case, repair and regeneration strategies. Generally, an ideal biomaterial should be biocompatible and bio-adhesive, possess adequate mechanical properties to tolerate the applied physiological load, and finally, show good bioactivity to ensure sufficient bonding at the material/tissue interface. The criteria for selecting the materials as biomaterials may be based on their chemistry, molecular weight, solubility, shape and structure, hydrophilicity/hydrophobicity, lubricity, surface energy, water absorption, and degradation properties. A strongly considered criteria to select a biomaterial for the development of 3D scaffolds is to match the mechanical properties and the degradation rate; this functions as a great opportunity to gradually support regeneration mechanisms as well as to release bioactive molecules and drugs by time and space controlled routes. In general, biodegradable/resorbable properties mainly refer to the susceptibility of a polymer to be decomposed by living organisms or by environmental factors. According to the ASTM (American Society for Testing and Materials) standard definition, biodegradable means “capable of undergoing decomposition into CO 2 , CH 4 , H 2 O, inorganic compounds or biomass”. In the restriction of tissue engineering use, biodegradable polymers have to be decomposed into biologically acceptable molecules—without the formation of harmful intermediate products—that can be metabolized and removed from the body via natural pathways (metabolism or excretion). Their ease of manufacturability, low cost, and customizable mechanical and physical properties make them useful for the fabrication of scaffolds by different processing techniques and modalities. Among biodegradable/bioresorbable polymers, it is possible to distinguish two different groups: natural and synthetic. The former one mainly includes proteins (i.e., collagens, zein, gelatin, elastin, silk fibroin) amides (i.e., starch) and polysaccharides (i.e., chitin, chitosan, alginates, cellulose derivates), which are macromolecules totally recognized in the biological microenvironment fully suitable for the regeneration of different tissues (i.e., nerve, cartilage, bone). Despite many advantages offered by materials from natural sources, notably biological recognition, synthetic polymers have often been preferred for their higher versatility in terms of properties’ variability and workability. In particular, relevant drawbacks in mechanical properties of natural polymers have imposed the use of synthetic ones to reach an acceptable balance between chemical stability and in vivo durability. However, many years of experimental studies have underlined that non-optimal cell interaction may be often an impenetrable limitation for the in vitro and in vivo applicability of scaffolds. Indeed, it is usually mandatory to assess chemical (i.e., molecular grafting) or physical (i.e., blending with natural polymers) modifications to generate their semi-synthetic counterparts, better recognized, even if not completely accepted into the implant site.