Tissue Engineering Based on Cell Sheet Technology

Recently, cell-based therapies, regenerative medicine, and tissue engineering have been progressing rapidly. With the injection of single cell suspensions, the injected cells are expected to remain around the damaged host tissues for the maintenance and recovery of native functions. Injections of bone marrow cells have been applied in many ways, and achieved some good clinical results. However, in most cases, the injected cells cannot be retained around the target tissue, causing difficulties to control the size, shape and location of the injected cells. To overcome these problems, biodegradable polymer scaffolds have been seeded with cells to be used to fabricate three-dimensional tissue-like grafts. Tissue engineering has been applied to epidermis, bone, cartilage, blood vessels, and heart valves. Various carrier materials such as collagen gels, fibrin gels, and amniotic membrane have been used to create epithelial grafts for the regeneration of epidermis, oral mucosal epithelium, and corneal epithelium. Upon polymer degradation, cells are believed to proliferate and migrate to replace the polymer scaffold. However, the places previously occupied by the polymer scaffolds are filled with large amount of extracellular matrix (ECM). Thus, cell-sparse tissues like cartilage or bone can be fabricated successfully. On the other hand, fabricated structures with biodegradable scaffolds cannot resemble cell-dense tissues such as heart and liver, and also cause pathological cases of fibrosis. For larger constructs, cells in the center of the constructs become necrotic though the cells on the periphery are unimpaired. This is due to the limits on passive diffusion, that is, insufficient delivery of oxygen and nutrients and removal of metabolic waste. Furthermore, strong inflammatory responses are often observed upon biodegradation of the scaffolds. Macrophages and neutrophils with collagenase and elastase activities migrate to the implant site during the early wound healing response. This host inflammatory response can damage the seeded cells even though the biodegradable scaffolds are non-toxic and mechanically non-invasive, resulting the failure of the engineered tissues. Therefore, a new method to avoid the use of bioP R O G R ES S R EP O R T