title: Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery.
abstract: Engineering new tissues utilizing cell transplantation on biodegradable polymer matrices is an attractive approach to treat patients suffering from the loss or dysfunction of a number of tissues and organs. The matrices must maintain structural integrity during the process of tissue formation, and promote the vascularization of the developing tissue. A number of molecules (angiogenic factors) have been identified that promote the formation of new vascular beds from endothelial cells present within tissues, and the localized, controlled delivery of these factors from a matrix may allow an enhanced vascularization of engineered tissues. We have developed a gas foaming polymer processing approach that allows the fabrication of three-dimensional porous matrices from bioabsorbable materials (e.g., copolymers of lactide and glycolide [PLG]) without the use of organic solvents or high temperatures. The effects of several processing parameters (e.g., gas type, polymer composition and molecular weight) on the process were studied. Several gases (CO(2), N(2), He) were utilized in the fabrication process, but only CO(2) resulted in the formation of highly porous, structurally intact matrices. Crystalline polymers (polylactide and polyglycolide) did not form porous matrices, while amorphous copolymers (50:50, 75:25, and 85:15 ratio of lactide:glycolide) foamed to yield matrices with porosity up to 95%. The mechanical properties of matrices were also regulated by the choice of PLG composition and molecular weight. Angiogenic factors (e.g., vascular endothelial growth factor) were subsequently incorporated into matrices during the fabrication process, and released in a controlled manner. Importantly, the released growth factor retains over 90% of its bioactivity. In summary, a promising system for the incorporation and delivery of angiogenic factors from three-dimensional, biodegradable polymer matrices has been developed, and the fabrication process allows incorporation under mild conditions.
authors.affiliation: Department of Biological & Materials Sciences, University of Michigan, Ann Arbor, MI 48109-1078, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Sheridan
authors.forename: L D
authors.initials: LD
authors.lastname: Shea
authors.forename: M C
authors.initials: MC
authors.lastname: Peters
authors.forename: D J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000042:Absorption; D001698:Biomedical Engineering; D002245:Carbon Dioxide / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D016228:Endothelial Growth Factors / Q000493:pharmacokinetics*; D006027:Glycosides / Q000737:chemistry; D006133:Growth Substances / Q000008:administration & dosage*; D006371:Helium / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D008222:Lymphokines / Q000493:pharmacokinetics*; D009584:Nitrogen / Q000737:chemistry; D011108:Polymers / Q000378:metabolism*; D016062:Porosity; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D003692:Delayed-Action Preparations; D016228:Endothelial Growth Factors; D006027:Glycosides; D006133:Growth Substances; D008222:Lymphokines; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D002245:Carbon Dioxide; D006371:Helium; D019344:Lactic Acid; D009584:Nitrogen