![]() Table 1.1 Characterization of scaffolds commonly used for liver engineering.įig. This approach is exemplified by the results presented in Figure 1.4. Such "high-fidelity" biomimetic systems for liver tissue engineering include blends of different natural and/or synthetic polymers, heterotypic cell populations, and a variety of growth factors required both for growth and differentiation of the hepatocytes and promotion of blood vessels ingrowth from the host into the scaffold to ensure long-term survival and function of the constructs. It is increasingly recognized that in aspiring to fully mimic and recreate in vitro the tissue environment, scaffolds, besides providing structural support for cell growth, are an integral part of bioactive, complex systems. Recently, the requirements for the design of liver scaffolds have become more sophisticated. Other important factors to be considered in the design of liver scaffolds are mechanical properties, such as elasticity and stability (Table 1.1). Pores of100 to 500 ^m diameter are optimal for hepatocyte growth, as they increase the internal surface area ofthe liver scaffold for optimized cell attachment and increased penetration of blood vessels. Scaffold porosity (see Table 1.1) is crucial for nutrient and gas exchange, which are essential for hepatocyte survival. In the context of liver tissue engineering it is also important that the scaffolds will be biodegradable - that is, they will be degraded and eliminated from the body, and also be bioerodible - that is, their degradation products will lack toxicity or immunogenicity (Table 1.1). Depending on its biological provenance and type or way of preparation, collagen may also induce an inflammatory response. While natural proteins, such as alginate and chitosan possess relative good biocompatibility, the biocompatibility of PLGA is transient and biphasic: over a short time period, PLGA is well tolerated, but it may produce inflammatory responses in the long term. In this context, biocompatibility is defined as the ability of a given material to perform with an appropriate host response in a specific biological application Based on a more complete understanding of the importance of cell-selective adhesion motifs, some of the above polymers have been modified chemically to increase their biocompatibility The most frequently used scaffolds for liver tissue engineering are made of synthetic biodegradable polymers such as PGA, PLA and PLGA, natural polymers such as collagen, alginate and chitosan, as well as several combinations of synthetic and/or natural polymers. Some of the critical issues in designing a liver scaffold are listed in Table 1.1. Following attachment, the cells must proliferate and finally differentiate in order to perform their physiological function. To facilitate these processes the scaffolds must provide a biocompatible surface suitable for cell recognition and adherence. In order to generate a functional liver construct, the liver cells, once seeded onto the scaffolds, must migrate into the scaffold interior, expand, and populate the new tissue constructs. ![]() In general, either mixed cultures of primary isolated cells or freshly isolated purified primary hepatocytes are applied to the scaffold. ![]()
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