Nanoenhanced hydrogel system with sustained release capabilities

An alginate/halloysite nanotube (HNT) nanocomposite was developed with sustained release of bone morphogenetic proteins (BMPs) at picogram low levels. BMP-2, 4, and 6 and osteoblasts were chosen as our model growth factor and cell type as the interaction of BMPs with osteoblasts is well known and thoroughly investigated. Alginate hydrogels with HNTs doped with BMP-2, 4, or 6 only or BMP-4 and 6 in combination. Osteoblasts were seeded within the hydrogels and studied for changes in cell proliferation, phenotypic expression, and mineralization over a 28-day experimental period. Osteoblast behavior was enhanced in BMP doped hydrogel/HNTs nanocomposites as compared with control groups. Release profiles showed that BMP-2 was released in a sustained fashion over a 7-day period and at picogram levels. Mineralization, as showed by Von Kossa staining, and protein synthesis peaked at 28 days, for all three growth factor combinations. BMP-4 provided a marked stimulus for osteoblast functionality base and was comparable to BMP-6 in terms of osteoblast differentiation and mineralization. BMP-4 and 6, in combination, showed a marked enhancement in osteoblast differentiation and functionality; however, the response seemed to be delayed when compared with BMP-4 and 6 release. Hydrogel surfaces had a complex surface topography and greater structural integrity with increased halloysite addition. The data suggest that these nanocomposites may provide a mechanism to enhance repair and regeneration in damaged or diseased tissues, reducing the need for more invasive treatment modalities. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103: 2416-2426, 2015.