Aims

Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro.

Nanotopographical cues on Ti surfaces have been shown to elicit different cell responses such as differentiation and selective growth. Bone remodelling is a continuous process requiring specific cues for optimal bone growth and implant fixation. In addition, the prevention of biofilm formation on surgical implants is a major challenge. We have identified nanopatterns on Ti surfaces that would be optimal for both bone remodelling and for reducing risk of bacterial infection. We used primary human osteoblast/osteoclast co-cultures and seeded them on flat Ti and three Ti nanosurfaces with increasing degrees of roughness, manufactured using anodisation under alkaline conditions (for 2, 2.5 and 3 hours). Cell growth and behaviour was assessed by scanning electron microscopy (SEM), immunofluorescence microscopy, histochemistry and quantitative RT-PCR methods. Bacterial growth on the nanowire surfaces was also assessed by confocal microscopy and SEM. From the three surfaces tested, the 2 h nanowire surface supported osteoblast and, to a lesser extent, osteoclast growth and differentiation. Bacterial viability was significantly reduced on the 2h surface. Hence the 2 h surface provided optimal bone remodelling conditions while reducing infection risk, making it a favourable candidate for future implant surfaces. This work was funded by EPSRC grant EP/K034898/1.

In biomaterial engineering the surface of an implant can influence cell differentiation, adhesion and affinity towards the implant. Increased bone marrow derived mesenchymal stromal cell (BMSC) differentiation towards bone forming osteoblasts, on contact with an implant, can improve osteointegration. The process of micropatterning has been shown to improve osteointegration in polymers, but there are few reports surrounding ceramics.

The purpose of this study was to establish a co-culture of BMSCs with osteoclast progenitor cells and to observe the response to micropatterned zirconia toughened alumina (ZTA) ceramics with 30 µm diameter pits. The aim was to establish if the pits were specifically bioactive towards osteogenesis or were generally bioactive and would also stimulate osteoclastogenesis that could potentially lead to osteolysis.

We demonstrate specific bioactivity of micropits towards osteogenesis with more nodule formation and less osteoclastogenesis. This may have a role when designing ceramic orthopaedic implants.

Background

Aseptic loosening remains the primary reason for failure of orthopaedic implants. Therefore a prime focus of Orthopaedic research is to improve osteointegration and outcomes of joint replacements. The topography of a material surface has been shown to alter cell adhesion, proliferation and growth. The use of nanotopography to promote cell adhesion and bone formation is hoped to improve osteointegration and outcomes of implants. We have previously shown that 15nm high features are bioactive. The arrangement of nanofeatures has been shown to be of importance and block-copolymer separation allows nanopillars to be anodised into the titania layer, providing a compromise of control of order and height of nanopillars. Osteoblast/osteoclast stem cell co-cultures are believed to give the most accurate representation of the in vivo environment, allowing assessment of bone remodelling related to biomaterials.