In vitro and in vivo response to nanotopographically-modified surfaces of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and polycaprolactone

Colloidal lithography and embossing master are new techniques of producing nanotopography, which have been recently applied to improve tissue response to biomaterials by modifying the surface topography on a nano-scale dimension. A natural polyester (Biopol™), 8% 3-hydroxyvalerate-component (D400G) and a conventional biodegradable polycaprolactone (PCL) were studied, both nanostructured and native forms, in vitro and in vivo. Nanopits (100-nm deep, 120-nm diameter) on the D400G surface were produced by the embossing master technique (Nano-D400G), while nanocylinders (160-nm height, 100-nm diameter) on the PCL surface were made by the colloidal lithography technique (Nano-PCL). L929 fibroblasts were seeded on polyesters, and cell proliferation, cytotoxic effect, synthetic and cytokine production were assessed after 72 h and 7 days. Then, under general anesthesia, 3 Sprague-Dawley rats received dorsal subcutaneous implants of nanostructured and native polyesters. At 1, 4 and 12 weeks the animals were pharmacologically euthanized and implants with surrounding tissue studied histologically and histomorphometrically. In vitro results showed significant differences between D400G and PCL in Interleukin-6 production at 72 h. At 7 days, significant (P < 0.05) differences were found in Interleukin-1 β and tumor necrosis factor-α release for Nano-PCL when compared to Nano-D400G, and for PCL in comparison with D400G. In vivo results indicated that Nano-D400G implants produced a greater extent of inflammatory tissue than Nano-PCL at 4 weeks. The highest vascular densities were observed for Nano-PCL at 4 and 12 weeks. Chemical and topographical factors seem to be responsible for the different behaviour, and from the obtained results a prevalence of chemistry on in vitro data and nanotopography on soft tissue response in vivo are hypothesized, although more detailed investigations are necessary in this field.