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 μm to 92.5 μm. 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 CO2 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.
Bibliographical noteFunding Information:
We are grateful to Dan Pack for helpful discussions on the microsphere fabrication. Funding for this project was provided by The Whitaker Foundation and the American Cancer Society—Illinois Division. LDS is a member of the Robert H. Lurie Comprehensive Cancer Center.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science