4.2. Tissue Engineering and Regenerative Medicine 4.2.1. Skin Establishing normal physiology and function in a traditional 2D in vitro cell culture of skin is almost impossible. The advent of organotypic culture systems does allow approximation of skin complexity. 3D culture of skin allows dermatological studies which would otherwise be unsafe for animals and humans such as validating the mechanisms of skin diseases and testing the therapeutic potential of experimental drugs [135]. Developing a 3D in vitro human skin co-culture model has shown promise for detecting skin irritants as an alternative to in vivo animal testing [136]. 4.2.2. Cartilage Specific signature gene cluster regulation was seen during in vitro chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells which were immobilized in a self-gelling alginate hydrogel. Upregulation of transcription factor genes as well as a signature cluster of extracellular matrix genes occurred during chondrogenesis while gene clusters involved in immune response, blood vessel development, and cell adhesion were downregulated [95]. Marker genes identified in this study show that stem cells can be directed to produce hyaline cartilage when immobilized in 3D alginate hydrogels. Immobilizing cells with chondrogenic potential in an alginate hydrogel has shown that neocartilage can be formed by mesenchymal stem cells [137]. Here, production of not only type II collagen but also assembled fibrils was dependent on cell seeding density. When cells were seeded at a high density, fibril assembly and procollagen processing occurred at a distance from the cell surface. 4.2.3. Cardiac Cardiac tissue engineering may involve the regeneration of myocardial tissue by first immobilizing stem cells in a scaffold or matrix in vitro and then placing such a scaffold on, or within, the damaged cardiac tissue. Immobilizing myocardial stem cells within a scaffold ensures that they will remain within the cardiac tissue after implantation. Ceccaldi et al. [138] has studied the influence of alginate composition on mesenchymal stem cells in alginate scaffolds. Their conclusion was the G-rich alginate hydrogels provided the most appropriate milieu for MSCs intended for cardiac therapy. Levit et al. [139] have shown similar results where alginate-encapsulated human mesenchymal stem cells were placed onto a rat heart as a hydrogel patch. The alginate hydrogel retained the MSCs and led to an improvement of cardiac function following induced myocardial infarct.