Furqan A. Shah

Commercially pure titanium (cp-Ti) versus titanium alloy (Ti6Al4V) materials as bone anchored implants - Is one truly better than the other?

Commercially pure titanium (cp-Ti) and titanium alloys (typically Ti6Al4V) display excellent corrosion resistance and biocompatibility. Although the chemical composition and topography are considered important, the mechanical properties of the material and the loading conditions in the host have, conventionally, influenced material selection for different clinical applications: predominantly Ti6Al4V in orthopaedics while cp-Ti in dentistry. This paper attempts to address three important questions: (i) To what extent do the surface properties differ when cp-Ti and Ti6Al4V materials are manufactured with the same processing technique?, (ii) Does bone tissue respond differently to the two materials, and (iii) Do bacteria responsible for causing biomaterial-associated infections respond differently to the two materials? It is concluded that: (i) Machined cp-Ti and Ti6Al4V exhibit similar surface morphology, topography, phase composition and chemistry, (ii) Under experimental conditions, cp-Ti and Ti6Al4V demonstrate similar osseointegration and biomechanical anchorage, and (iii) Experiments in vitro fail to disclose differences between cp-Ti and Ti6Al4V to harbour Staphylococcus epidermidis growth. No clinical comparative studies exist which could determine if long-term, clinical differences exist between the two types of bulk materials. It is debatable whether cp-Ti or Ti6Al4V exhibit superiority over the other, and further comparative studies, particularly in a clinical setting, are required.

Long-term osseointegration of 3D printed CoCr constructs with an interconnected open-pore architecture prepared by electron beam melting

UNLABELLED In orthopaedic surgery, cobalt chromium (CoCr) based alloys are used extensively for their high strength and wear properties, but with concerns over stress shielding and bone resorption due to the high stiffness of CoCr. The structural stiffness, principally related to the bulk and the elastic modulus of the material, may be lowered by appropriate design modifications, to reduce the stiffness mismatch between metal/alloy implants and the adjacent bone. Here, 3D printed CoCr and Ti6Al4V implants of similar macro-geometry and interconnected open-pore architecture prepared by electron beam melting (EBM) were evaluated following 26week implantation in adult sheep femora. Despite higher total bone-implant contact for Ti6Al4V (39±4%) than CoCr (27±4%), bone formation patterns were similar, e.g., densification around the implant, and gradual ingrowth into the porous network, with more bone in the outer half (periphery) than the inner half (centre). Raman spectroscopy revealed no major differences in mineral crystallinity, the apatite-to-collagen ratio, or the carbonate-to-phosphate ratio. Energy dispersive X-ray spectroscopy showed similar Ca/P ratio of the interfacial tissue adjacent to both materials. Osteocytes made direct contact with CoCr and Ti6Al4V. While osteocyte density and distribution in the new-formed bone were largely similar for the two alloys, higher osteocyte density was observed at the periphery of the porous network for CoCr, attributable to slower remodelling and a different biomechanical environment. The results demonstrate the possibility to achieve bone ingrowth into open-pore CoCr constructs, and attest to the potential for fabricating customised osseointegrated CoCr implants for load-bearing applications. STATEMENT OF SIGNIFICANCE Although cobalt chromium (CoCr) based alloys are used extensively in orthopaedic surgery, stress shielding due to the high stiffness of CoCr is of concern. To reduce the stiffness mismatch between CoCr and bone, CoCr and Ti6Al4V implants having an interconnected open-pore architecture were prepared by electron beam melting (EBM). After six months of submerged healing in sheep, both alloys showed similar patterns of bone formation, with densification around the implant and gradual ingrowth into the porous network. The molecular and elemental composition of the interfacial tissue was similar for both alloys. Osteocytes made direct contact with both alloys, with similar overall osteocyte density and distribution. The work attests to the potential for achieving osseointegration of EBM manufactured porous CoCr implants.

The bone-implant interface – nanoscale analysis of clinically retrieved dental implants

UNLABELLED Evaluation of the fine structure of the bone-implant interface in humans is a prerequisite for a deepened understanding of structure-function relationships with nano-modified biomaterials. In this study, three clinically stable, yet retrieved, laser-modified dental implants were evaluated using histological and interface ultrastructural analyses. The cumulative results for all threads containing intact tissue showed remodeled Haversian bone with bone area and bone-implant contact in excess of 85% and 80%, respectively. Collagen fibrils, laid down parallel to the surface oxide layer, were mineralized by plate-like crystallites of stoichiometrically relevant (Ca/P ratios 1.30-1.67) bone-apatite. An overlap of titanium, oxygen, calcium and phosphorus signals indicated the gradual intermixing of bone-apatite and the nano-rough surface oxide. These results suggest that bone bonding to nano-textured titanium implant surfaces is promoted in human jaw-bone after functional loading. FROM THE CLINICAL EDITOR In this study, newly developed and laser-modified titanium dental implants demonstrate strong evidence for implant-osseo integration basen on the surface and chemical analysis of three clinically stable dental implants.

Laser-Modified Surface Enhances Osseointegration and Biomechanical Anchorage of Commercially Pure Titanium Implants for Bone-Anchored Hearing Systems

Osseointegrated implants inserted in the temporal bone are a vital component of bone-anchored hearing systems (BAHS). Despite low implant failure levels, early loading protocols and simplified procedures necessitate the application of implants which promote bone formation, bone bonding and biomechanical stability. Here, screw-shaped, commercially pure titanium implants were selectively laser ablated within the thread valley using an Nd:YAG laser to produce a microtopography with a superimposed nanotexture and a thickened surface oxide layer. State-of-the-art machined implants served as controls. After eight weeks’ implantation in rabbit tibiae, resonance frequency analysis (RFA) values increased from insertion to retrieval for both implant types, while removal torque (RTQ) measurements showed 153% higher biomechanical anchorage of the laser-modified implants. Comparably high bone area (BA) and bone-implant contact (BIC) were recorded for both implant types but with distinctly different failure patterns following biomechanical testing. Fracture lines appeared within the bone ~30–50 μm from the laser-modified surface, while separation occurred at the bone-implant interface for the machined surface. Strong correlations were found between RTQ and BIC and between RFA at retrieval and BA. In the endosteal threads, where all the bone had formed de novo, the extracellular matrix composition, the mineralised bone area and osteocyte densities were comparable for the two types of implant. Using resin cast etching, osteocyte canaliculi were observed directly approaching the laser-modified implant surface. Transmission electron microscopy showed canaliculi in close proximity to the laser-modified surface, in addition to a highly ordered arrangement of collagen fibrils aligned parallel to the implant surface contour. It is concluded that the physico-chemical surface properties of laser-modified surfaces (thicker oxide, micro- and nanoscale texture) promote bone bonding which may be of benefit in situations where large demands are imposed on biomechanically stable interfaces, such as in early loading and in compromised conditions.

Ultrastructural evaluation of shrinkage artefacts induced by fixatives and embedding resins on osteocyte processes and pericellular space dimensions

The integrity of the interface between the osteocyte (Ot) process and the canalicular wall was investigated in terms of change in the lateral dimensions of the Ot process in relation to the canalicular width, i.e., widening of the pericellular space. This has been interpreted as shrinkage of the Ot process relative to the canalicular wall during sample preparation stages of fixation, dehydration, and resin embedding. Sprague-Dawley rat tibial cross-sections were prepared for transmission electron microscopy (TEM). Four different fixative preparations: paraformaldehyde (PF), modified Karnovskys (MK), glutaraldehyde (GRR) with ruthenium red (GRR), and zinc formalin (ZF); and two different embedding resins: LR Gold (LRG) and Epon812 (Epon) were evaluated. It was found that for LRG embedding, formalin-only fixatives (PF and ZF) induced lower shrinkage than GRR-containing fixatives (MK and GRR). In contrast, for Epon embedding, MK showed the highest shrinkage, while no differences were found between the remaining fixatives (PF, ZF, and GRR). All formalin-containing fixatives (MK, PF, and ZF) induced similar shrinkage in both embedding media. The most dramatic difference was for GRR fixation, which in combination with LRG embedding showed ∼ 62% more shrinkage than with Epon embedding, suggesting that the combination of GRR fixation and LRG embedding synergistically amplifies Ot shrinkage. These differences likely suggest a role of the resin in secondarily influencing the tissue structure following fixation. Further, the work confirms LRG as a poor embedding medium for bone specimens, as it causes large variations in shrinkage depending on fixation.

Fluoride-containing bioactive glasses: Glass design, structure, bioactivity, cellular interactions, and recent developments.

Bioactive glasses (BGs) are known to bond to both hard and soft tissues. Upon exposure to an aqueous environment, BG undergoes ion exchange, hydrolysis, selective dissolution and precipitation of an apatite layer on their surface, which elicits an interfacial biological response resulting in bioactive fixation, inhibiting further dissolution of the glass, and preventing complete resorption of the material. Fluorine is considered one of the most effective in-vivo bone anabolic factors. In low concentrations, fluoride ions (F(-)) increase bone mass and mineral density, improve the resistance of the apatite structure to acid attack, and have well documented antibacterial properties. F(-) ions may be incorporated into the glass in the form of calcium fluoride (CaF2) either by part-substitution of network modifier oxides, or by maintaining the ratios of the other constituents relatively constant. Fluoride-containing bioactive glasses (FBGs) enhance and control osteoblast proliferation, differentiation and mineralisation. And with their ability to release fluoride locally, FBGs make interesting candidates for various clinical applications, dentinal tubule occlusion in the treatment of dentin hypersensitivity. This paper reviews the chemistry of FBGs and the influence of F(-) incorporation on the thermal properties, bioactivity, and cytotoxicity; and novel glass compositions for improved mechanical properties, processing, and bioactive potential.

A technique for evaluating bone ingrowth into 3D printed, porous Ti6Al4V implants accurately using X-ray micro-computed tomography and histomorphometry

This paper investigates the application of X-ray micro-computed tomography (micro-CT) to accurately evaluate bone formation within 3D printed, porous Ti6Al4V implants manufactured using Electron Beam Melting (EBM), retrieved after six months of healing in sheep femur and tibia. All samples were scanned twice (i.e., before and after resin embedding), using fast, low-resolution scans (Skyscan 1172; Bruker micro-CT, Kontich, Belgium), and were analysed by 2D and 3D morphometry. The main questions posed were: (i) Can low resolution, fast scans provide morphometric data of bone formed inside (and around) metal implants with a complex, open-pore architecture?, (ii) Can micro-CT be used to accurately quantify both the bone area (BA) and bone-implant contact (BIC)?, (iii) What degree of error is introduced in the quantitative data by varying the threshold values?, and (iv) Does resin embedding influence the accuracy of the analysis? To validate the accuracy of micro-CT measurements, each data set was correlated with a corresponding centrally cut histological section. The results show that quantitative histomorphometry corresponds strongly with 3D measurements made by micro-CT, where a high correlation exists between the two techniques for bone area/volume measurements around and inside the porous network. On the contrary, the direct bone-implant contact is challenging to estimate accurately or reproducibly. Large errors may be introduced in micro-CT measurements when segmentation is performed without calibrating the data set against a corresponding histological section. Generally, the bone area measurement is strongly influenced by the lower threshold limit, while the upper threshold limit has little or no effect. Resin embedding does not compromise the accuracy of micro-CT measurements, although there is a change in the contrast distributions and optimisation of the threshold ranges is required.

Electropolished Titanium Implants with a Mirror-Like Surface Support Osseointegration and Bone Remodelling

This work characterises the ultrastructural composition of the interfacial tissue adjacent to electropolished, commercially pure titanium implants with and without subsequent anodisation, and it investigates whether a smooth electropolished surface can support bone formation in a manner similar to surfaces with a considerably thicker surface oxide layer. Screw-shaped implants were electropolished to remove all topographical remnants of the machining process, resulting in a thin spontaneously formed surface oxide layer and a smooth surface. Half of the implants were subsequently anodically oxidised to develop a thickened surface oxide layer and increased surface roughness. Despite substantial differences in the surface physicochemical properties, the microarchitecture and the composition of the newly formed bone were similar for both implant surfaces after 12 weeks of healing in rabbit tibia. A close spatial relationship was observed between osteocyte canaliculi and both implant surfaces. On the ultrastructural level, the merely electropolished surface showed the various stages of bone formation, for example, matrix deposition and mineralisation, entrapment of osteoblasts within the mineralised matrix, and their morphological transformation into osteocytes. The results demonstrate that titanium implants with a mirror-like surface and a thin, spontaneously formed oxide layer are able to support bone formation and remodelling.

Osseointegration of 3D printed microalloyed CoCr implants-Addition of 0.04% Zr to CoCr does not alter bone material properties: OSSEOINTEGRATION OF 3D PRINTED MICROALLOYED COBALT CHROMIUM

Electron beam melting (EBM) is a three-dimensional (3D) printing technique for the production of metal structures where complex geometries with interconnected porosities can be built. Incorporation of as little as 0.04% Zr into the CoCr alloy can significantly improve the biomechanical anchorage of constructs fabricated by EBM. Here we investigate bone material properties, including microstructure and composition, adjacent to 3D printed CoCr implants with and without addition of 0.04% Zr, after 8 weeks of healing in the rabbit femur. In low amounts, zirconium addition does not alter the microstructure and extracellular matrix composition of bone formed adjacent to the surface of EBM manufactured implants. Bone ingrowth into surface irregularities of 3D printed CoCr and CoCr + Zr implants is seen. Extensive remodeling is also evident. Osteocytes attach directly on to the implant surface. The interfacial tissue at CoCr and CoCr + Zr has similar mineral crystallinity, apatite-to-collagen ratio, carbonate-to-phosphate ratio, Ca/P ratio, bone-implant contact, percentage porosity, and osteocyte density (N.Ot/B.Ar). Compared to the native bone, the mineral crystallinity of the interfacial tissue was lower while N.Ot/B.Ar was higher for both CoCr and CoCr + Zr. Overall, the results indicate that bone tissue adjacent to CoCr and CoCr + Zr implants is highly mature and exhibits comparable healing kinetics.

Multiscale characterization of cortical bone composition, microstructure, and nanomechanical properties in experimentally induced osteoporosis

Cortical bone plays a vital role in determining overall bone strength. We investigate the structural, compositional, and nanomechanical properties of cortical bone following ovariectomy (OVX) of 12-week-old Sprague Dawley rats, since this animal model is frequently employed to evaluate the performance of implantable biomaterials in compromised bone healing conditions. Morphological parameters and material properties of bone in the geometrical center of the femoral cortex were investigated four and eight weeks post-OVX and in unoperated controls (Ctrl), using X-ray micro-computed tomography, backscattered electron scanning electron microscopy, Raman spectroscopy, and nanoindentation. The OVX animals showed increase in body weight, diminished bone mineral density, increased intracortical porosity, but increased bone mass through periosteal apposition (e.g., increases in periosteal perimeter, cortical cross-sectional thickness, and cross-sectional area). However, osteocyte densities, osteocyte lacunar dimensions, and the nanomechanical behavior on the single mineralized collagen fibril level remained unaffected. Our correlative multiscale investigation provides structural, chemical, and nanomechanical evidence substantiating earlier reports suggesting that rats ovariectomized at 12 weeks undergo simultaneous bone loss and growth, resulting in the effects of OVX being less obvious. Periosteal apposition contradicts the conventional view of bone loss in osteoporosis but appears advantageous for the greater functional demand imposed on the skeleton by increased body weight and fragility induced by increased intracortical porosity. Through a variety of morphological changes, it is likely that 12-week-old rats are able to adapt to OVX-related microstructural and compositional alterations.