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The scaffold, earlier called a matrix, is a three-dimensional material composed of either chemically fabricated materials or native molecules. In tissue engineering, it provides a framework on which cells organize so that they can execute the repairing or replacing function. The scaffold is one of the three essential components necessary to construct a biological substitute; others are cells and a bioreactor in which the cells and scaffold become integrated. A wide range of permanent or biodegradable materials has been used to scaffold biological components. Since the ideal scaffolds used in tissue engineering must be able to actively interact with biological components that house the seeded cells, they should possess certain surface properties, sufficient space, and mechanical strength that favor cell adhesion, promote cell growth, and facilitate differentiated functions.

Several types of scaffolding materials are used for different tissue-engineering approaches. Metals and ceramics are useful scaffolds for orthopedic tissue replacement. To execute regenerative functions under most circumstances, their sole role is to provide mechanical support without the involvement of biological materials.

The dominant scaffolds in tissue-engineering research and development are polymer materials because they are close in composition to native structures as well as being able to degrade and form the shapes desired for a particular application. In regard to their chemical natures, they can be synthetized in laboratories or exist as naturally derived products or biopolymers. Synthetic polymers, such as polyglycolic acid, polylactic acid, copolymer polylactic-co-glycolic acid, and polyurethane, have been the primary choice for many tissue-engineering applications. Under most environments in which the cells or tissue grow, synthetic scaffolds can be hydrolyzed into monomers that can be easily metabolized into end products and then eliminated. During this process, cells or tissues of interest are able to organize themselves and form a new biological body.

The significant advantage of the synthetic polymers is that they possess reasonable mechanical strength, they have controllable degradation timeframe, and most importantly, they can be easily formed into desired shapes for a variety of organ replacements. They can also be made into micro- or macroporous forms ranging from 15 to 200 m in diameter or into fiber meshes. Recently, three-dimensional printing has been introduced into scaffold fabrication; this process relies on an ink-jet printing repeat process to form a porous scaffold objective for tissue-engineering application. These characteristics make them capable of accommodating functional cells.

However, most synthetic polymers lack biocompatibility and do not coordinate well with surrounding biological components since, sooner or later, they elicit inflammation and immunogenicity. Efforts have been made to improve these issues by cross-linking other molecules in favor of their targeted functional aspects. For example, if negative charges of the carboxyl groups on synthetic polymers are added on the surface of vascular prosthesis, the antithrombogenicity and durability will be increased.

Researchers expect that natural materials, or biopolymers, such as polypeptide derivatives like collagen, fibrin, laminin, fibronectin, silk, and polysaccharide chitosan, can have the complex composition close to native molecules and recapitulate in vivo microenvironments, thus improve functional performance. The drawbacks of biopolymers are their inability to be degraded in a controllable manner and their lack of strong mechanical properties. Consequently, cells or tissues do not easily reorganize to become a viable organ with a predefined shape for transplantation.

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