Harnessing Nanotopography to Enhance Osseointegration of Clinical Orthopedic Titanium Implants-An and Analysis.

Despite technological advancements, further innovations in the field of orthopedics and bone regeneration are essential to meet the rising demands of an increasing aging population and associated issues of disease, injury and trauma. Nanotopography provides new opportunities for novel implant surface modifications and promises to deliver further improvements in implant performance. However, the technical complexities of nanotopography fabrication and surface analysis have precluded identification of the optimal surface features to trigger osteogenesis.

Gelatin freeze casting of biomimetic titanium alloy with anisotropic and gradient pore structure.

Titanium is a material commonly used for dental and orthopaedic implants. However, due to large differences in properties between the titanium metal and the natural bone, stress shielding has been observed in the surrounding area, resulting in bone atrophy, and thus has raised concerns of the use of this material. Ideally implant materials should possess similar properties to the surrounding tissues in order to distribute the load as the joint would naturally, while also possessing a similar porous structure to the bone to enable interaction with the surrounding material.

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.

Cicada-inspired cell-instructive nanopatterned arrays.

Biocompatible surfaces hold key to a variety of biomedical problems that are directly related to the competition between host-tissue cell integration and bacterial colonisation. A saving solution to this is seen in the ability of cells to uniquely respond to physical cues on such surfaces thus prompting the search for cell-instructive nanoscale patterns. Here we introduce a generic rationale engineered into biocompatible, titanium, substrates to differentiate cell responses.

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.

Investigation of the limits of nanoscale filopodial interactions.

Mesenchymal stem cells are sensitive to changes in feature height, order and spacing. We had previously noted that there was an inverse relationship between osteoinductive potential and feature height on 15-, 55- and 90 nm-high titania nanopillars, with 15 nm-high pillars being the most effective substrate at inducing osteogenesis of human mesenchymal stem cells. The osteoinductive effect was somewhat diminished by decreasing the feature height to 8 nm, however, which suggested that there was a cut-off point, potentially associated with a change in cell-nanofeature interactions.

Embossing of micropatterned ceramics and their cellular response.

The aim of this work is to investigate the use of microtopographies in providing physical cues to modulate the cellular response of human mesenchymal stem cells on ceramics. Two microgrooved patterns (100 μm/50 μm, 10 μm/10 μm groove/pitch) were transcribed reversely onto alumina green ceramic tapes via an embossing technique followed by sintering. Characterization of the micropatterned alumina surfaces and their cellular response was carried out.

2D and 3D nanopatterning of titanium for enhancing osteoinduction of stem cells at implant surfaces.

The potential for the use of well-defined nanopatterns to control stem cell behaviour on surfaces has been well documented on polymeric substrates. In terms of translation to orthopaedic applications, there is a need to develop nanopatterning techniques for clinically relevant surfaces, such as the load-bearing material titanium (Ti). In this work, a novel nanopatterning method for Ti surfaces is demonstrated, using anodisation in combination with PS-b-P4VP block copolymer templates.

Titanium nanofeaturing for enhanced bioactivity of implanted orthopedic and dental devices.

Titanium (Ti) is used as a load-bearing material in the production of orthopedic devices. The clinical efficacy of these implants could be greatly enhanced by the addition of nanofeatures that would improve the bioactivity of the implants, in order to promote in situ osteo-induction and -conduction of the patient's stem and osteoprogenitor cells, and to enhance osseointegration between the implant and the surrounding bone. Nanofeaturing of Ti is also currently being applied as a tool for the biofunctionalization of commercially available dental implants.

Novel anodization technique using a block copolymer template for nanopatterning of titanium implant surfaces.

Precise surface nanopatterning is a promising route for predictable control of cellular behavior on biomedical materials. There is currently a gap in taking such precision engineered surfaces from the laboratory to clinically relevant implant materials such as titanium (Ti). In this work, anodization of Ti surfaces was performed in combination with block copolymer templates to create highly ordered and tunable oxide nanopatterns.

Metabolomics: a valuable tool for stem cell monitoring in regenerative medicine.

Metabolomics is a method for investigation of changes in the global metabolite profile of cells. This paper discusses the technical application of the approach, considering metabolite extraction, separation, mass spectrometry and data interpretation. A particular focus is on the application of metabolomics to the study of stem cell physiology in the context of biomaterials and regenerative medicine.

Skeletal stem cell physiology on functionally distinct titania nanotopographies.

Functionalisation of the surface of orthopaedic implants with nanotopographies that could stimulate in situ osteogenic differentiation of the patient's stem or osteoprogenitor cells would have significant therapeutic potential. Mesenchymal stem cell (MSC) responses to titanium substrates patterned with nanopillar structures were investigated in this study. Focal adhesions were quantified in S-phase cells, the bone-related transcription factor Runx2 was examined, osteocalcin production was noted, and Haralick computational analysis was used to assess the relatedness of the cell responses to each of the titanium substrata based on cytoskeletal textural features.

The synergistic effects of lysophosphatidic acid receptor agonists and calcitriol on MG63 osteoblast maturation at titanium and hydroxyapatite surfaces.

Successful osseointegration stems from the provision of a mechanically competent mineralised matrix at the implant site. Mature osteoblasts are the cells responsible for achieving this and a key factor for ensuring healthy bone tissue is associated with prosthetic materials will be 1 alpha,25 dihydroxy vitamin D3 (calcitriol). However it is known that calcitriol per se does not promote osteoblast maturation, rather the osteoblasts need to be in receipt of calcitriol in combination with selected growth factors in order to undergo a robust maturation response.

Through-mask anodization of titania dot- and pillar-like nanostructures on bulk Ti substrates using a nanoporous anodic alumina mask.

Nanosized surface topography on an implant material has the capability of stimulating the acceptance of the material in its host surrounding. Fine-tuning of nanotopography feature size has been shown to trigger differentiation of mesenchymal stem cells into bone cells in vitro. For this purpose we have created well defined nanosized titania dot- and pillar-like structures on mechanically polished Ti substrates using a through-mask anodization technique with an anodic porous alumina template.

Fabrication of pillar-like titania nanostructures on titanium and their interactions with human skeletal stem cells.

Surface nanotopography is known to influence the interaction of human skeletal (mesenchymal) stem cells (hMSC) with a material surface. While most surface nanopatterning has been performed on polymer-based surfaces there is a need for techniques to produce well-defined topography features with tuneable sizes on relevant load-bearing implant materials such as titanium (Ti). In this study titania nanopillar structures with heights of either 15, 55 or 100 nm were produced on Ti surfaces using anodization through a porous alumina mask.