scaffold; the insert shows a SEM micrograph of PLGA microspheres (round spheres) before incorporation into the alginate scaffold. (D) A hematoxylin and eosin-stained section through the alginate composite scaffold center, demonstrating the survival and hepatic-like organization of the seeded hepatocytes 3 days after implantation.

Macroscopic scaffolds (Fig. 1.4A) were generated by controlled lyophilization; the porous nature of these scaffolds is shown in Figure 1.4B. PLGA microspheres containing angiogenic growth factors such as bFGF [77] or VEGF [78, 79] (Fig. 1.4C, insert) were incorporated into alginate scaffolds during the lyophilization process, without interfering with the porosity of the scaffold; in this way they became an integral part ofthe alginate matrix (Fig. 1.4C). These scaffolds were then implanted on one of the liver lobes of Lewis rats, enabling a short initial angiogenic process. After one week ofprevascularization, primary hepatocytes [80] were seeded into the implanted VEGF-releasing scaffolds. The hepatocytes in these constructs survived for up to two weeks, and organized in a histiotypic fashion in vivo (Fig. 1.4D) [76]. These proof-of-concept studies attest to the feasibility of liver tissue engineering.

However, the long-term goal of extending hepatocyte survival and function in the implanted constructs requires further investigation. Furthermore, the results of these studies suggest that engineered liver constructs could also provide a suitable model for discovery and in-vitro testing of liver-specific drugs and therapeutic modalities.

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