Jang Jae-Hyung, Shea Lonnie D
Department of Chemical Engineering, Northwestern University, 2145 Sheridan Rd, E156, Evanston, IL 60208-3120, USA.
J Control Release. 2003 Jan 9;86(1):157-68. doi: 10.1016/s0168-3659(02)00369-3.
The inductive approach to tissue engineering combines three-dimensional porous scaffolds with drug delivery to direct the action of progenitor cells into a functional tissue. We present an approach to fabricate scaffolds capable of controlled, sustained delivery by the assembly and subsequent fusion of drug-loaded microspheres using a gas foaming/particulate leaching process. DNA-loaded microspheres were fabricated from the copolymers of lactide and glycolide (PLG) using a cryogenic double emulsion process. Microspheres were fabricated in four populations with mean diameters ranging from 12.3 microm to 92.5 microm. Scaffolds fabricated by fusion of these microspheres had an interconnected open pore structure, maintained DNA integrity, and exhibited sustained release for 21 days. Control over the release was obtained through manipulating the properties of the polymer, microspheres, and the foaming process. Decreasing the microsphere diameter or the molecular weight of the polymer used for microsphere fabrication led to increased rates of release from the porous scaffold. Additionally, increasing the pressure of CO(2) increased the DNA release rate. The ability to create porous polymer scaffolds capable of controlled release rates may provide a means to enhance and regulate gene transfer within a developing tissue, which will increase their utility in tissue engineering.
组织工程学的归纳法将三维多孔支架与药物递送相结合，以引导祖细胞的作用形成功能性组织。我们提出了一种通过使用气体发泡/颗粒沥滤工艺组装并随后融合载药微球来制造能够进行可控、持续递送的支架的方法。使用低温双乳液工艺由丙交酯和乙交酯的共聚物（PLG）制备载DNA微球。制备了四个群体的微球，平均直径范围为12.3微米至92.5微米。通过融合这些微球制备的支架具有相互连通的开孔结构，保持了DNA的完整性，并表现出持续21天的释放。通过操纵聚合物、微球和发泡工艺的性质来实现对释放的控制。减小微球直径或用于制备微球的聚合物的分子量会导致多孔支架的释放速率增加。此外，增加CO₂的压力会提高DNA释放速率。创建能够控制释放速率的多孔聚合物支架的能力可能提供一种增强和调节发育中组织内基因转移的手段，这将增加它们在组织工程学中的实用性。
