Tissue engineering scaffolds for controlled protein and plasmid delivery

Tissue engineering approaches employ polymer scaffolds to supports, promote, and direct tissue formation by progenitor cells, which are either present in the surrounding tissue or transplanted with the polymer. We hypothesize that scaffolds capable of delivering tissue-inductive factors, or genes encoding for these factors, at the correct time and location, and in the appropriate concentration could enhance the effectiveness of current regenerative approaches. Scaffolds have been developed that provide a controlled, sustained delivery of protein and non-viral DNA. Polymeric scaffolds capable of sustained drug release can be fabricated by the assembly of drug-loaded microspheres and subsequent fusion of the microspheres using a gas foaming process. This process has been developed to regulate the amount released and the release rates for protein, naked DNA, and DNA complexed with cationic lipid and polymers. Alternatively, we have developed a controlled DNA delivery system based on the tethering of DNA complexes to a biomaterial surfaces. Complexes can be immobilized at high densities and cells cultured on the substrates can internalize and express the DNA. These systems for the controlled delivery of proteins, or DNA-encoding for these proteins, are versatile and can be readily applied to the regeneration of various tissues.