Investigations into Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Surface Properties Causing Delayed Osteoblast Growth

Osteoblast proliferation is sensitive to the topography of material surfaces. In this study, the proliferation of MC3T3 E1-S14 osteoblast cells on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) films with different surface characteristics was investigated. The solvent cast films were prepared using three different solvents/solvent mixtures; chloroform, DCM and a mixture of chloroform and acetone which produced PHBV films with both a rough (at the air interface) and smooth (at the glass interface) surface. Investigation of the surface characteristics by scanning electron and scanning probe microscopies revealed different surface topographies and degrees of surface roughness ranging from 20 to 200 nm. Mapping of the surface crystallinity index by micro-attenuated total reflectance Fourier transform infrared (ATR-FTIR) showed distinct variations in surface crystallinity between the different film surfaces. Water contact angles were significantly higher on the rough surface compared the smooth surface for a particular substrate, however, all surfaces were hydrophobic in nature (θA was in the range 69 - 80 degrees). MC3T3 E1-S14 osteoblast cells were cultured on the six different surfaces and proliferation was determined. After 2 days cell proliferation on all surfaces was significantly less than on the control substrate, however, after 4 days cell proliferation was optimal on the three surfaces that displayed the highest contact angle and the smallest crystallinity heterogeneity. In addition, the surface roughness and more specifically the surface topography influenced the proliferation of osteoblast cells on the PHBV film surface

Treatment with a long-acting chimeric CSF1 molecule enhances fracture healing of healthy and osteoporotic bones

Macrophage-targeted therapies, including macrophage colony-stimulating factor 1 (CSF1), have been shown to have pro-repair impacts post-fracture. Preclinical/clinical applications of CSF1 have been expedited by development of chimeric CSF1-Fc which has extended circulating half-life. Here, we used mouse models to investigate the bone regenerative potential of CSF1-Fc in healthy and osteoporotic fracture. We also explored whether combination of CSF1-Fc with interleukin (IL)-4 provided additional fracture healing benefit in osteopenic bone. Micro-computed tomography, in situ histomorphometry, and bone mechanical parameters were used to assess systemic impacts of CSF1-Fc therapy in naive mice (male and female young, adult and geriatric). An intermittent CSF1-Fc regimen was optimized to mitigate undesirable impacts on bone resorption and hepatosplenomegaly, irrespective of age or gender. The intermittent CSF1-Fc regimen was tested in a mid-diaphyseal femoral fracture model in healthy bones with treatment initiated 1-day post-fracture. Weekly CSF1-Fc did not impact osteoclasts but increased osteal macrophages and improved fracture strength. Importantly, this treatment regimen also improved fracture union and strength in an ovariectomy-model of delayed fracture repair. Combining CSF1-Fc with IL-4 initiated 1-week post-fracture reduced the efficacy of CSF1-Fc. This study describes a novel strategy to specifically achieve bone regenerative actions of CSF1-Fc that has the potential to alleviate fragility fracture morbidity and mortality.</p