Tissue engineering is an emerging multidisciplinary and interdisciplinary field involving the development of bioartificial implants and/or the fostering of tissue remodeling with the purpose of repairing or enhancing tissue or organ function. Bioartificial constructs generally consist of cells and biomaterials, so tissue engineering draws from both cell and biomaterials science and technology. Successful applications require a thorough understanding of the environment experienced by cells in normal tissues and by cells in bioartificial devices before and after implantation. This paper reviews these topics, as well as the current status and future possibilities in the development of different bioartificial constructs, including bioartificial skin, cardiovascular implants, bioartificial pancreas, and encapsulated secretory cells. Issues that need to be addressed in the future are also discussed. These include, but are not limited to, the development of new cell lines and biomaterials, the evaluation of the optimal construct architecture, and the reproducible manufacture and preservation of bioartificial devices until ready for use.

The implantation of laboratory-grown tissue offers a valuable alternative approach to the treatment of cartilage defects. Procuring sufficient cell numbers for such tissue-engineered cartilage is a major problem since amplification of chondrocytes in culture typically leads to loss of normal cell phenotype yielding cartilage of inferior quality. In an effort to overcome this problem, we endeavored to regain the differentiated phenotype of chondrocytes after extensive proliferation in monolayer culture by modulating cell morphology and oxygen tension towards the in vivo state. Passaged cells were encapsulated in alginate hydrogel in an effort to regain the more rounded shape characteristic of differentiated chondrocytes. These cultures were exposed to reduced (5%-i.e., physiological), or control (20%) oxygen tensions. Both alginate encapsulation and reduced oxygen tension significantly upregulated collagen II and aggrecan core protein expression (differentiation markers). In fact, after 4 weeks in alginate at 5% oxygen, differentiated gene expression was comparable to primary chondrocytes. Collagen I expression (dedifferentiation marker) decreased dramatically after alginate entrapment, while reduced oxygen tension had no effect. It is concluded that alginate encapsulation and reduced oxygen tension help restore key differentiated phenotypic markers of passaged chondrocytes. These findings have important implications for cartilage tissue engineering, since they enable the increase in differentiated cell numbers needed for the in vitro development of functional cartilaginous tissue suitable for implantation.

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