Development of degradable polyesterurethanes for medical applications: in vitro and in vivo evaluations

To evaluate the biocompatibility of a newly developed degradable class of polyesterurethanes and their possible use as biomaterials, we investigated the cell and tissue interactions with these polymers using a small number of chemical base entities. The polymers were prepared by chain extension with diisocyanates of PHB/HV-diol and either PCL-diol or Diorez, another aliphatic polyester-diol. Regardless of the chemical composition of the four tested polyesterurethanes used as substrates, no morphological difference was observed either in the macrophages (macrophage cell line J774) or in the fibroblasts (fibroblast cell line 3T3) cultured on the polymers. In contrast, however, cell adhesion and growth of macrophages and fibroblasts were affected by the polymer properties. Compared to macrophages cultured on tissue culture polystyrene (TCPS), cells cultured on the test polymers exhibited levels of cell adhesion that varied from 65-100% of TCPS, and the doubling time was 25-43% higher on the polymers than on TCPS. Likewise, fibroblasts adhered to the polymers at lower rates (50-85% of TCPS) and grew at higher doubling times (125-140% of TCPS). Furthermore, cells cultured on the test polymers preserved their phenotypes: fibroblasts produced high amounts (up to 280% of control cells) of collagens Type I and Type IV and fibronectin; and macrophages produced nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) in the same concentrations as control cells and responded to lipopolysaccharide treatment by the elevation of the production of NO and TNF-alpha, indicating that the cell-to-polymer interactions allow fibroblasts and macrophages to maintain their phenotypes. In vivo investigations showed that all four test polymers exhibit favorable tissue compatibility. The formed capsule was 60-250 microns thick. In addition, the polymers are degradable. After one year's subcutaneous implantation in rats, the molecular weight of the test polymers were reduced to about 50%, depending on the composition. Taken collectively, the present data demonstrate that the newly developed polyesterurethanes are cell and tissue compatible and biodegradable.