Chapter 069. Tissue Engineering (Part 2)

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Scaffolds A scaffold provides a three-dimensional framework to support the tissue or organ-specific cells. The scaffold not only provides mechanical support, but it must also supply critical nutrients and transport metabolites to and from the developing tissue. Important scaffold properties vary depending on the tissue but typically include specific biomechanical properties, porosity, biocompatibility, and appropriate surface characteristics for cell adhesion and differentiation. Scaffolds can be natural materials or synthetic polymers and are typically biodegradable. Natural materials such as collagen and alginates are biocompatible. However, it is difficult to control their mechanical properties, and they may generate an immune reaction. ...

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Chapter 069. Tissue Engineering (Part 2) Scaffolds A scaffold provides a three-dimensional framework to support the tissue or organ-specific cells. The scaffold not only provides mechanical support, but it must also supply critical nutrients and transport metabolites to and from the developing tissue. Important scaffold properties vary depending on the tissue but typically include specific biomechanical properties, porosity, biocompatibility, and appropriate surface characteristics for cell adhesion and differentiation. Scaffolds can be natural materials or synthetic polymers and are typically biodegradable. Natural materials such as collagen and alginates are biocompatible. However, it is difficult to control their mechanical properties, and they may generate an immune reaction. Synthetic polymers such as polyglycolic acid and polyethylene, on the other hand, can be tailored to provide more acceptable
mechanical properties but are associated with a strong inflammatory response. Nonbiodegradable synthetic polymers such as polytetrafluoroethylene and polyethylene provide well-defined mechanical and structural properties. However, their long-term presence in the body can lead to a chronic inflammatory response, which results in poor tissue quality. Polylactic acid and polyglycolic acid are examples of biodegradable polymers. Although the degradation of these materials can be partially controlled, nonuniform degradation and varying degradation rates in different anatomic locations represent challenges. The surface properties of the materials used for the scaffold are important for adhesion, migration, and cell differentiation. Ongoing research is focused on tethering growth factors or peptide sequences to the surface of the scaffold to improve adhesion and migration. Bioreactors Initially, cells used in tissue engineering were cultured in static conditions. Improvements in bioreactor technology more closely approximate physiologic parameters for tissue growth. By modulating rates of flow and mixing, the transfer of nutrients, gases, metabolites, and regulatory molecules can be maximized. Mechanical stimuli can also impact the newly forming tissue. For example, tissue- engineered blood vessels exposed to shear stress in a pulsatile flow bioreactor
have greater burst strength and collagen content than those not exposed to shear stress. Tissue Engineering Successes Several tissue-engineered skin substitutes have been approved by the U.S. Food and Drug Administration (FDA) and in use for >10 years (Table 69-1). One of these products uses neonatal dermal fibroblasts isolated from human foreskins cultured on a scaffold of polylactide coglycolide. The polymer scaffold gradually degrades in the presence of water. A bilayer skin substitute has also been developed: dermal fibroblasts are cultured in a collagen solution and then coated with several layers of keratinocytes. Cartilage tissue engineering is also showing promise; autologous chondrocytes from a healthy portion of the patient's joint are expanded in culture and then implanted into the site of injury. Other scaffold- based products are based on processed animal submucosa or dura. In addition to these FDA-approved products, numerous tissue-engineered products are currently in clinical trials (Table 69-2). Engineered tissues being actively investigated include bone, mandible, teeth, cartilage, skin, cornea, bladder, urethra, small- diameter blood vessels, and the pulmonary artery. Table 69-1 FDA-Approved Tissue-Engineered Products
Name of Product Brief Description Alloderm (LifeCell) Acellular dermal matrix for tissue repair Apligraf Living skin equivalent approved for the (Organogenesis) treatment of venous leg ulcers and diabetic foot ulcers Carticel (Genzyme Autologous chondrocytes approved for Biosurgery) cartilage repair Dermagraft (Smith Living skin equivalent approved for full- and Nephew) thickness diabetic foot ulcers Durasis (Cook Porcine small-intestine submucosa for Surgical Products) replacement of dura mater Epicel (Genzyme Living skin equivalent approved for burn Biosurgery) patients OrCel (Ortec) Living skin equivalent approved for burn
patients Surgisis (Cook Porcine small-intestine submucosa for dermal Surgical Products) wounds and reinforcement of weakened tissue