Fabrication of Scaffolds for Tissue Engineering

As discussed above, an ideal scaffold for tissue engineering must provide the necessary mechanical/structural support and contain the appropriate instructive/ differentiative cues, such as the capability of inducing neovascularization, to allow the tissue-engineered construct to be integrated into the host surroundings [47]. Most scaffolds presently being investigated in animal research promote some cellular ingrowth, and may hence be quite useful for in-vitro applications. Overall, however, most of these scaffolds pose significant limitations to host integration in situ, including a host-versus-graft immunological response, and do not offer a very effective basis for organ replacement. Therefore, there is a need to develop novel scaffolds and approaches.

In addition to using hydrogel-based scaffolds made of collagen or fibrin, several novel techniques have been developed for engineering 3D "solid" scaffolds with enhanced mechanical properties. The microscopic/nanoscale structure and function of biological macromolecules constituting conventional hydrogels are important for cell physiology. However, the relatively weak mechanical properties of hydrogel scaffolds pose a major drawback, especially in vivo. Thus, diverse "solid" scaffolds, made of water-soluble polymers (collagen, fibrin, and alginate) with improved mechanical properties have been engineered using controlled freezing and thawing procedures, followed by crosslinking. Such scaffolds have shown excellent biocompatibility and facilitated excellent cellular ingrowth both in vitro and in vivo. More recently, solid nano/microfibrous scaffolds have been generated by electrospinning or acellularization (see Section 1.3.1). These fibrous scaffolds more realistically emulate salient structural and biological features of the natural ECM, and seem to be very well suited as substrates for 3D tissue engineering purposes, both in in vitro and in vivo. One of advantages of 3D nanofibrous scaffolds is the small diameter of the fibers, which is similar to the diameters of ECM proteins in situ. Such small fiber diameters provide a relatively large surface-to-volume ratio, enabling the absorption of liquids and facilitating cellular attachment and cell-cell interaction. These scaffolds also exhibit unique mechanical properties which permit better cell penetration and proliferation within the scaffolds as compared to 3D hydrogels. Recent data have suggested the possibility of generating hybrid scaffolds for cardiac tissue engineering by combining hydrogel and solid scaffolds comprised of both synthetic and natural biopolymers such as PLGA, collagen, or elastin [13].

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