Highly porous bioresorbable scaffolds with controlled release of bioactive agents for tissue-regeneration applications.

Abstract

Highly porous poly(DL-lactic-co-glycolic acid) films with controlled release of horseradish peroxidase (HRP) as a model protein have been successfully developed and studied. These films, which are prepared by freeze-drying inverted emulsions, are designed for use in tissue-regeneration applications. The effects of the emulsion's formulation and host polymer's characteristics on the film's microstructure and HRP release profile over 4 weeks were investigated. A dual pore size population is characteristic for most films, with large 12-18 microm pores and small 1.5-7 microm pores, and porosity in the range of 76-92%. An increase in the polymer content and its initial molecular weight, organic/aqueous (O:A) phase ratio and lactic acid content, or a decrease in the HRP content, all resulted in a decreased burst effect and a more moderate release profile. A simultaneous change in two or three of these formulation parameters (compared to a reference formulation) resulted in a synergistic effect on the HRP release profile. A constant HRP release rate was achieved when a composite film was used. Human gingival fibroblast adhesion to the films indicated good biocompatibility. Appropriate selection of the emulsion's parameters can therefore yield highly porous films with the desired protein-release behavior which can serve as scaffolds for bioactive agents in tissue-regeneration applications.