Biomaterials For Genitourinary Tissue Engineering

Biomaterials should provide a three-dimensional space for cells to form into new tissues; they should allow for delivery of the desired cells for tissue replacement and appropriate bioactive factors (cell adhesion peptides, growth factors) to desired sites in the body, and guide the development of new tissues with appropriate function (6).

In tissue engineering, a scaffold that allows cell adherence and regeneration is essential. The materials that are used as scaffolding should replicate the biologic and mechanical function of the native extracellular matrix.

The majority of mammalian cell types are anchorage-dependent and must have a cell-adhesion substrate for survival; biomaterials provide a cell-adhesion substrate that can deliver cells to specific sites in the body with high loading efficiency. The scaffolding also provides mechanical support against in vivo forces, thereby maintaining the integrity of the predefined structure until the cells have matured into the desired three-dimensional structure.

A foreign body response should be avoided as it leads to rejection and/or necrosis and ultimately failure of the graft. As the scaffolding is metabolized by the host, its degradation products should be nontoxic, nonimmunogenic, and removed from the host at the appropriate rate such that the concentrations of these products remain at a tolerable level. Furthermore, the biomaterial should provide an environment in which cell behavior is not altered. Cell adhesion, proliferation, migration, and differentiation should promote functional tissue formation.

The ideal biomaterial should also be biocompatible. The biomaterial should persist for an appropriate amount of time to allow for adequate replacement of normal tissue, but it should be absorbed by the host without inflammation.

The naturally derived materials have the potential advantage of cellular recognition and biologic response. However, synthetic polymers can be reproduced on a large scale with controlled properties of strength, degradation rate, and microstructure.

Collagen, the most abundant structural protein in the body, is readily purified from both animal and human tissues with an enzyme treatment and salt/acid extraction. Collagen generates minimal inflammatory response, and it has been approved by the U.S. Food and Drug Administration for many types of medical applications, including wound dressings and artificial skin. Collagen implantation is limited by its relatively rapid degradation from sequential attacks by lysosomal enzymes. Acellular tissue matrices are collagen-rich matrices prepared by mechanical and/or chemical removal of the cellular components from tissues leaving only the supportive scaffolding behind. This artificial extracellular membrane slowly degrades after implantation and is replaced by true extracellular matrix proteins synthesized and secreted by transplanted or ingrowing cells.

Three basic classes of biomaterials have been utilized in the engineering of genitourinary organs: naturally-derived materials (e.g., collagen and alginate), acellular tissue matrices (e.g., bladder submucosa and small intestinal submucosa), and synthetic polymers [e.g., polyglycolic acid, polylactic acid, and poly(lactic-co-glycolic acid)].

Alginate, a polysaccharide isolated from seaweed, has been used as an injectable cell delivery vehicle and a cell immobilization matrix owing to its gentle gelling properties in the presence of divalent ions such as calcium. Alginate is limited by its lack of a biologic recognition domain and limited range of mechanical properties.

Polyesters of naturally occurring alpha-hydroxy acids, including polyglycolic acid, polylactic acid, and polylactic glycolic acid, are used widely in tissue engineering. The Food and Drug Administration has approved the use of these polymers for a multitude of clinical applications including sutures. These polymers contain ester bonds, which are hydrolytically labile, allowing their degradation by nonenzymatic hydrolysis. Their degradation byproducts are nontoxic—natural metabolites that are eliminated from the

The success of using cell transplantation strategies for bladder reconstruction depends on the ability to use donor tissue efficiently and to provide the right conditions for long-term survival, differentiation, and growth.

The augmented bladders demonstrated cellular organization consisting of a trilayer of urothelium, submucosa, and muscle.

Laparoscopic bladder augmentation is being done in humans; however, laparoscopic bladder augmentation with engineered tissue has only recently been described in animal models.

host in the form of water and carbon dioxide. These materials can be constructed such that they degrade in several weeks to several years by altering the crystallinity, initial molecular weight, and the copolymer ratio of lactic to glycolic acid. Also, these polymers are thermoplasts, which allows them to be formed into the appropriate three dimensional scaffolds with a desired microstructure, gross shape, and dimension by various techniques, including molding, extrusion, solvent casting, phase separation techniques, and gas foaming techniques. These techniques can be used to process biomaterials into porous sponges and fiber meshes, which have high porosity and a high surface area-to-volume ratio; these properties enhance the effectiveness of the scaffold. Other biodegradable synthetic polymers including poly(anhydrides) and poly(ortho-esters) also can be used to fabricate scaffolds for genitourinary tissue engineering with controlled properties.

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