ABSTRACT
In order to control and direct cell behavior, a well-defined biomimetic environment, which surrounds the cells and promotes specific cell interactions, is necessary. Scaffold properties depend primarily on the nature of the biomaterial and the fabrication process. The nature of the biomaterial has been the subject of extensive studies including different materials such as natural, synthetic materials, ceramics, or composite of these compounds.Natural materials provide a more physiological environment for celladhesion and proliferation and may be further divided intoprotein-based matrices such as collagen and fibrin, and carbohydrate-basedmatrices such as alginate, agarose, chitosan, and hyaluronan [24-26]. Natural materials are biocompatible, biodegradable and they have the ability to mimic certain aspects of native ECM, thus facilitating cell adhesion, migration, differentiation, and ECM deposition. However, natural materials have several disadvantages such as immunogenecity, difficulty in processing, and a potential risk of transmitting animal-originated pathogens. Moreover, despite the biocompatibility, these materials
are mechanically weak and undergo rapid degradation upon implantation if not cross-linked with appropriate chemical reagents [27]. 11.3 View within Article Synthetic materials have been used extensively both in vitroand in vivo due to their easy moldingcharacteristics, relatively easy production, and the abilityto control dissolution and degradation they are fully employed in tissue engineering [28]. The most popular biodegradable synthetic polymers include poly(a-hydroxy acids), especially poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and their co-polymers (PLGA), poly(e-caprolactone), poly(propylene fumarate), poly(dioxanone) [29].Although synthetic materials are biocompatible, they do not have natural sites for cell adhesion,and these often need to be added. Further, their in vivo degradation by a hydrolyticreaction causes a local reduction inpH and possible inflammation response [30].Ceramics, such as hydroxyapatite (HA) or other calcium phosphate (Ca-P) ceramics (including tricalcium phosphate, TCP) or bioactive glasses are known to promote, when implanted, the formation of a bone-like apatite layer on their surfaces [31, 32]. They have been investigated extensively during the last decades and are widely used for bone replacement, due to their osteoconductivity and high biocompatibility, also associated with stem cells therapy [19].The main purpose for osteochondral TE is to recreate a more biomimetic scaffold combining synthetic materials with cell-recognition sites of naturally derived materials [31, 33, 34]. In addition, looking to the architectures of native tissues, novel graded scaffolds represent the challenge for osteochondral defect treatment. In fact bone and cartilage have complete different properties. For bone, mechanically stiff biomaterials with options for medium perfusion and vascularization are required to support cell expansion, as well as the production of bone matrix rich in type I collagen and hydroxyapatite. By contrast, native cartilage matrix consists of an avascular highly hydrated proteoglycan hydrogel embedded into a type II collagen network.
