Porous PLGA scaffolds for controlled release of naked and polyethyleneimine-complexed DNA

The ability to precisely control delivery of single or multiple bioactive molecules is critical in tissue engineering, and controlled release of plasmid coding for growth factors and their regulators can give cell-regulated, short-term expression of these therapeutic biomolecules. In this work, porous poly(lactic-co-glycolic acid) (PLGA) scaffolds comprising acid-terminated chains of either low (LMW; 10 kDa) or high molecular weight (HMW; 30 kDa) were developed for controlled release of naked or polyethyleneimine (PEI)-complexed DNA. The compressive strength of blank HMW and LMW scaffolds was 6 and 2 MPa, respectively, while the strength of PEI:DNA-containing HMW and LMW scaffolds was 7 and 1 MPa, respectively. LMW scaffolds degraded more quickly than HMW scaffolds, with 80–100% and 15–30% mass loss at 30 days, respectively. Encapsulation of plasmid, particularly PEI-complexed DNA, only modestly affected degradation. Release profiles showed bi- or triphasic patterns, with early burst release of surface-associated DNA, slower diffusion-mediated release, and degradation-related release at later time points. Complexation with PEI tended to a slow release of plasmids, likely because of interaction with the carboxyl groups of PLGA. Culturing rat bone marrow cells on blank PLGA scaffolds in the presence of IGF-I resulted in growth and chondrogenic differentiation of these cells. Porous scaffolds made of PLGA with the appropriate selection of hydrophobicity and molecular weight will allow controlled delivery of naked and condensed plasmid DNA for different tissue engineering applications. (paper)