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enhancement or defect correction in an existing model. Many tools also support the ability to compare different versions of the lower-level models, when they are regenerated from the same high-level model. For example, suppose we use a CDM to generate an LDM and then later modify the CDM and regenerate our LDM (based on this modi ed CDM). Many tools will provide a merge facility to compare the newly generated LDM with the previously generated version. Such a facility would allow us to identify differences between versions in order to avoid overwriting any additional details added to the rst LDM after it was generated. This is important, since there are always additional details needed for the lower-level DMs that are not speci ed in the higher-level DMs these details are often manually added after the LDM is generated. Therefore, both automatic forward generation and interactive merge facilities are very useful facilities to have in a modeling tool. Even when manual techniques are used for FE, the ability to generate multiple LDMs and PDMs from the same CDM is a terri c advantage, when compared to generating multiple database models completely from scratch. If the models are intended to be used as different implementations of the same system, then they should capture and represent the same semantic details (even if the implementation and enforcement is different across the different deployed systems). Using a single, consistent CDM as a source provides an easy mechanism for tracing the requirements through the analysis, design, and implementation phases for these environments.

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regenerative environment, which would be dif cult to control in a clinical setting Furthermore, survival and engraftment of transplanted hepatocytes has been reported to be quite low, only 20 30% [Gupta et al, 1999b] Several studies have demonstrated methods to improve engraftment and enhance the selective proliferation of transplanted hepatocytes [Guha et al, 1999; Joseph et al, 2002; Laconi et al, 1998; Malhi et al, 2002; Mignon et al, 1998; Slehria et al, 2002], although the clinical utility of these approaches remains to be determined As an alternative to mature hepatocytes, numerous stem cell populations are currently being investigated as potential cell sources, including pluripotent embryonic stem cells and various adult stem cell types One adult stem cell of interest is the hepatic oval cell, which mediates liver regeneration in certain cases of severe and chronic liver injury [Oh et al.

, 2002; Sell, 2001] Oval cells exhibit bipotential differentiation, de ned by the ability to differentiate into both hepatocytes and bile duct epithelial cells Oval cells can be isolated and signi cantly expanded in culture [Petersen et al, 1998; Yang et al, 2002], and, furthermore, recent experiments in mice illustrate the oval cell-mediated therapeutic repopulation of the liver [Wang et al, 2003] Elucidation of the mechanisms regulating the proliferation and hepatic differentiation of oval cells, as well as other stem cell populations, could lay the groundwork for the development of robust cell-based liver transplantation therapies Another cell-based strategy for liver treatment is the implantation of hepatocellular constructs Similar to various tissue engineering schemes in other organ systems, for this approach in the liver, hepatocytes are cultured within or immobilized on synthetic or biological scaffolds and surgically implanted [Allen and Bhatia, 2002].

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Substantial current research is focused on the development of scaffolds that promote proper hepatic function It is clear that several hepatocyte processes, such as survival and morphogenesis, can be in uenced by the scaffold characteristics [Demetriou et al, 1986a; Dixit et al, 1992; Dvir-Ginzberg et al, 2003; Elcin et al, 1998; Glicklis et al, 2000; Hasirci et al, 2001; Kim et al, 1998; Li et al, 2003; Pollok et al, 1998; Powers and Grif th, 1998; Ranucci et al, 2000; Risbud et al, 2003] Consequently, one signi cant challenge for the future is the design of platforms that enable the highly speci ed regulation of cellular orientations in three dimensions, as well as the controlled incorporation into the host environment.

A recent study utilizing a focused laser to activate locally a photolabile hydrogel structure demonstrated the patterned immobilization of an adhesive peptide, GRGDS, which subsequently exhibited a guidance effect on neurite growth [Luo and Shoichet, 2004] Several other techniques have also been used to pattern hydrogel networks, including micro uidics [Koh et al, 2003; Tan and Desai, 2003] and photolithography [Beebe et al, 2000; Koh et al, 2002; Ward et al, 2001; Yu and Ober, 2003] Our laboratory has developed an adaptation of standard photolithography techniques resulting in the photopatterning of hydrogel structures containing living cells [Liu and Bhatia, 2002] (See Section 7) In addition, our laboratory has recently demonstrated the dielectrophoretic positioning of cells within a hydrogel in the 10- m range [Albrecht et al, 2002] and the combination of this technique with the photopatterning procedure described here [Albrecht et al, 2005] Notably,.