Peter S Young

Analysis of Osteoclastogenesis/Osteoblastogenesis on Nanotopographical Titania Surfaces

A focus of orthopedic research is to improve osteointegration and outcomes of joint replacement. Material surface topography has been shown to alter cell adhesion, proliferation, and growth. The use of nanotopographical features to promote cell adhesion and bone formation is hoped to improve osteointegration and clinical outcomes. Use of block-copolymer self-assembled nanopatterns allows nanopillars to form via templated anodization with control over height and order, which has been shown to be of cellular importance. This project assesses the outcome of a human bone marrow-derived co-culture of adherent osteoprogenitors and osteoclast progenitors on polished titania and titania patterned with 15 nm nanopillars, fabricated by a block-copolymer templated anodization technique. Substrate implantation in rabbit femurs is performed to confirm the in vivo bone/implant integration. Quantitative and qualitative results demonstrate increased osteogenesis on the nanopillar substrate with scanning electron microscopy, histochemical staining, and real-time quantitative reverse-transcription polymerase chain reaction analysis performed. Osteoblast/osteoclast co-culture analysis shows an increase in osteoblastogenesis-related gene expression and reduction in osteoclastogenesis. Supporting this in vitro finding, in vivo implantation of substrates in rabbit femora indicates increased implant/bone contact by ≈20%. These favorable osteogenic characteristics demonstrate the potential of 15 nm titania nanopillars fabricated by the block-copolymer templated anodization technique.

Osteoclastogenesis/osteoblastogenesis using human bone marrow-derived cocultures on nanotopographical polymer surfaces.

BACKGROUND Optimised nanotopography with controlled disorder (NSQ50) has been shown to stimulate osteogenesis and new bone formation in vitro. Following osteointegration the implant interface must undergo constant remodeling without inducing immune response. AIM We aimed to assess the effect of nanotopography on bone remodelling using osteoclast and osteoblast cocultures. MATERIALS & METHODS We developed a novel osteoblast/osteoclast coculture using solely human bone marrow derived mesenchymal and hematopeotic progenitor cells without extraneous supplementation. The coculture was been applied to NSQ50 or flat control polycarbonate substrates and assessed using immunohistochemical and immunofluorescent microscopy, scanning electron microscopy and quantitative reverse-transcription PCR methods. RESULTS These confirm the presence of mature osteoclasts, osteoblasts and bone formation in coculture. Osteoblast differentiation increased on NSQ50, with no significant difference in osteoclast differentiation. CONCLUSION Controlled disorder nanotopography appears to be selectively bioactive. We recommend this coculture method to be a better in vitro approximation of the osseous environment encountered by implants.

Scanning electron microscopical observation of an osteoblast/osteoclast co-culture on micropatterned orthopaedic ceramics

In biomaterial engineering, the surface of an implant can influence cell differentiation, adhesion and affinity towards the implant. On contact with an implant, bone marrow–derived mesenchymal stromal cells demonstrate differentiation towards bone forming osteoblasts, which 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 bone marrow–derived mesenchymal stromal cells with osteoclast progenitor cells and to observe the response to micropatterned zirconia toughened alumina ceramics with 30 µm diameter pits. The aim was to establish whether 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 micropatterns towards osteogenesis, with more nodule formation and less osteoclastogenesis compared to planar controls. In addition, we found that that macrophage and osteoclast-like cells did not interact with the pits and formed fewer full-size osteoclast-like cells on the pitted surfaces. This may have a role when designing ceramic orthopaedic implants.

Antibacterial surface modification of titanium implants in orthopaedics

The use of biomaterials in orthopaedics for joint replacement, fracture healing and bone regeneration is a rapidly expanding field. Infection of these biomaterials is a major healthcare burden, leading to significant morbidity and mortality. Furthermore, the cost to healthcare systems is increasing dramatically. With advances in implant design and production, research has predominately focussed on osseointegration; however, modification of implant material, surface topography and chemistry can also provide antibacterial activity. With the increasing burden of infection, it is vitally important that we consider the bacterial interaction with the biomaterial and the host when designing and manufacturing future implants. During this review, we will elucidate the interaction between patient, biomaterial surface and bacteria. We aim to review current and developing surface modifications with a view towards antibacterial orthopaedic implants for clinical applications.