The interaction of phosphate species with cerium oxide: The known, the ambiguous and the unexplained.

Cerium oxide based nanozymes are intensively studied due to their catalytic activity and structural flexibility. Such nanozymes have a great future potential in human therapeutics and antimicrobial activity. The structural complexity of their surfaces enables a great variety of enzyme mimetic activities. However, selection of a specific activity remains challenging, as such activities are sensitive to morphological and compositional changes as well as the physicochemical and biological environments. When delivered into biological systems, many processes occur at the surface, redefining the biological identity and activity of the nanozyme. Inorganic phosphates and phosphate-bearing molecules are some critical examples of items that can interact with cerium oxide nanozymes. Inorganic phosphates can interact directly with cerium oxide and even have a scavenging activity converting the material into cerium phosphate. Phosphate-bearing molecules can absorb on the surface of the nanozyme where phosphatase activity may occur. Given the abundance of phosphates in biological environments, cerium oxide nanozymes are strongly affected by their local concentration. Here, we discuss the interaction of cerium oxide with phosphates and phosphate-bearing molecules, providing a focussed review of the computational and experimental literature, with a focus on the surface morphology and chemistry of the nanozyme and their impact on the phosphate adsorption and phosphatase activity.

Emerging Medical Technologies and Their Use in Bionic Repair and Human Augmentation.

As both the proportion of older people and the length of life increases globally, a rise in age-related degenerative diseases, disability, and prolonged dependency is projected. However, more sophisticated biomedical materials, as well as an improved understanding of human disease, is forecast to revolutionize the diagnosis and treatment of conditions ranging from osteoarthritis to Alzheimer's disease as well as impact disease prevention. Another, albeit quieter, revolution is also taking place within society: human augmentation. In this context, humans seek to improve themselves, metamorphosing through self-discipline or more recently, through use of emerging medical technologies, with the goal of transcending aging and mortality. In this review, and in the pursuit of improved medical care following aging, disease, disability, or injury, we first highlight cutting-edge and emerging materials-based neuroprosthetic technologies designed to restore limb or organ function. We highlight the potential for these technologies to be utilized to augment human performance beyond the range of natural performance. We discuss and explore the growing social movement of human augmentation and the idea that it is possible and desirable to use emerging technologies to push the boundaries of what it means to be a healthy human into the realm of superhuman performance and intelligence. This potential future capability is contrasted with limitations in the right-to-repair legislation, which may create challenges for patients. Now is the time for continued discussion of the ethical strategies for research, implementation, and long-term device sustainability or repair.

Multifunctional scaffolds for bone repair following age-related biological decline: Promising prospects for smart biomaterial-driven technologies.

The repair of large bone defects due to trauma, disease, and infection can be exceptionally challenging in the elderly. Despite best clinical practice, bone regeneration within contemporary, surgically implanted synthetic scaffolds is often problematic, inconsistent, and insufficient where additional osteobiological support is required to restore bone. Emergent smart multifunctional biomaterials may drive important and dynamic cellular crosstalk that directly targets, signals, stimulates, and promotes an innate bone repair response following age-related biological decline and when in the presence of disease or infection. However, their role remains largely undetermined. By highlighting their mechanism/s and mode/s of action, this review spotlights smart technologies that favorably align in their conceivable ability to directly target and enhance bone repair and thus are highly promising for future discovery for use in the elderly. The four degrees of interactive scaffold smartness are presented, with a focus on bioactive, bioresponsive, and the yet-to-be-developed autonomous scaffold activity. Further, cell- and biomolecular-assisted approaches were excluded, allowing for contemporary examination of the capabilities, demands, vision, and future requisites of next-generation biomaterial-induced technologies only. Data strongly supports that smart scaffolds hold significant promise in the promotion of bone repair in patients with a reduced osteobiological response. Importantly, many techniques have yet to be tested in preclinical models of aging. Thus, greater clarity on their proficiency to counteract the many unresolved challenges within the scope of aging bone is highly warranted and is arguably the next frontier in the field. This review demonstrates that the use of multifunctional smart synthetic scaffolds with an engineered strategy to circumvent the biological insufficiencies associated with aging bone is a viable route for achieving next-generation therapeutic success in the elderly population.

A neoteric antibacterial ceria-silver nanozyme for abiotic surfaces.

Community-associated and hospital-acquired infections caused by bacteria continue to yield major global challenges to human health. Bacterial contamination on abiotic surfaces is largely spread via high-touch surfaces and contemporary standard disinfection practices show limited efficacy, resulting in unsatisfactory therapeutic outcomes. New strategies that offer non-specific and broad protection are urgently needed. Herein, we report our novel ceria-silver nanozyme engineered at a molar ratio of 5:1 and with a higher trivalent (Ce3+) surface fraction. Our results reveal potent levels of surface catalytic activity on both wet and dry surfaces, with rapid, and complete eradication of Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin resistant S. aureus, in both planktonic and biofilm form. Preferential electrostatic adherence of anionic bacteria to the cationic nanozyme surface leads to a catastrophic loss in both aerobic and anaerobic respiration, DNA damage, osmodysregulation, and finally, programmed bacterial lysis. Our data reveal several unique mechanistic avenues of synergistic ceria-Ag efficacy. Ag potentially increases the presence of Ce3+ sites at the ceria-Ag interface, thereby facilitating the formation of harmful H2O2, followed by likely permeation across the cell wall. Further, a weakened Ag-induced Ce-O bond may drive electron transfer from the Ec band to O2, thereby further facilitating the selective reduction of O2 toward H2O2 formation. Ag destabilizes the surface adsorption of molecular H2O2, potentially leading to higher concentrations of free H2O2 adjacent to bacteria. To this end, our results show that H2O2 and/or NO/NO2-/NO3- are the key liberators of antibacterial activity, with a limited immediate role being offered by nanozyme-induced ROS including O2•- and OH•, and likely other light-activated radicals. A mini-pilot proof-of-concept study performed in a pediatric dental clinic setting confirms residual, and continual nanozyme antibacterial efficacy over a 28-day period. These findings open a new approach to alleviate infections caused by bacteria for use on high-touch hard surfaces.

Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection.

The human skeleton is a metabolically active system that is constantly regenerating via the tightly regulated and highly coordinated processes of bone resorption and formation. Emerging evidence reveals fascinating new insights into the role of sphingolipids, including sphingomyelin, sphingosine, ceramide, and sphingosine-1-phosphate, in bone homeostasis. Sphingolipids are a major class of highly bioactive lipids able to activate distinct protein targets including, lipases, phosphatases, and kinases, thereby conferring distinct cellular functions beyond energy metabolism. Lipids are known to contribute to the progression of chronic inflammation, and notably, an increase in bone marrow adiposity parallel to elevated bone loss is observed in most pathological bone conditions, including aging, rheumatoid arthritis, osteoarthritis, and osteomyelitis. Of the numerous classes of lipids that form, sphingolipids are considered among the most deleterious. This review highlights the important primary role of sphingolipids in bone homeostasis and how dysregulation of these bioactive metabolites appears central to many chronic bone-related diseases. Further, their contribution to the invasion, virulence, and colonization of both viral and bacterial host cell infections is also discussed. Many unmet clinical needs remain, and data to date suggest the future use of sphingolipid-targeted therapy to regulate bone dysfunction due to a variety of diseases or infection are highly promising. However, deciphering the biochemical and molecular mechanisms of this diverse and extremely complex sphingolipidome, both in terms of bone health and disease, is considered the next frontier in the field.

3D printed bioabsorbable composite scaffolds of poly (lactic acid)-tricalcium phosphate-ceria with osteogenic property for bone regeneration.

The fabrication of customized implants by additive manufacturing has allowed continued development of the personalized medicine field. Herein, a 3D-printed bioabsorbable poly (lactic acid) (PLA)- ß-tricalcium phosphate (TCP) (10 wt %) composite has been modified with CeO2 nanoparticles (CeNPs) (1, 5 and 10 wt %) for bone repair. The filaments were prepared by melt extrusion and used to print porous scaffolds. The nanocomposite scaffolds possessed precise structure with fine print resolution, a homogenous distribution of TCP and CeNP components, and mechanical properties appropriate for bone tissue engineering applications. Cell proliferation assays using osteoblast cultures confirmed the cytocompatibility of the composites. In addition, the presence of CeNPs enhanced the proliferation and differentiation of mesenchymal stem cells; thereby, increasing alkaline phosphatase (ALP) activity, calcium deposition and bone-related gene expression. Results from this study have shown that the 3D printed PLA-TCP-10%CeO2 composite scaffold could be used as an alternative polymeric implant for bone tissue engineering applications: avoiding additional/revision surgeries and accelerating the regenerative process.

Extracellular Proteins Isolated from L. acidophilus as an Osteomicrobiological Therapeutic Agent to Reduce Pathogenic Biofilm Formation, Regulate Chronic Inflammation, and Augment Bone Formation In Vitro.

Periprosthetic joint infection (PJI) is a challenging complication that can occur following joint replacement surgery. Efficacious strategies to prevent and treat PJI and its recurrence remain elusive. Commensal bacteria within the gut convey beneficial effects through a defense strategy named "colonization resistance" thereby preventing pathogenic infection along the intestinal surface. This blueprint may be applicable to PJI. The aim is to investigate Lactobacillus acidophilus spp. and their isolated extracellular-derived proteins (LaEPs) on PJI-relevant Staphylococcus aureus, methicillin-resistant S. aureus, and Escherichia coli planktonic growth and biofilm formation in vitro. The effect of LaEPs on cultured macrophages and osteogenic, and adipogenic human bone marrow-derived mesenchymal stem cell differentiation is analyzed. Data show electrostatically-induced probiotic-pathogen species co-aggregation and pathogenic growth inhibition together with LaEP-induced biofilm prevention. LaEPs prime macrophages for enhanced microbial phagocytosis via cathepsin K, reduce lipopolysaccharide-induced DNA damage and receptor activator nuclear factor-kappa B ligand expression, and promote a reparative M2 macrophage morphology under chronic inflammatory conditions. LaEPs also significantly augment bone deposition while abating adipogenesis thus holding promise as a potential multimodal therapeutic strategy. Proteomic analyses highlight high abundance of lysyl endopeptidase, and urocanate reductase. Further, in vivo analyses are warranted to elucidate their role in the prevention and treatment of PJIs.

Promising applications of D-amino acids in periprosthetic joint infection.

Due to the rise in our aging population, a disproportionate demand for total joint arthroplasty (TJA) in the elderly is forecast. Periprosthetic joint infection (PJI) represents one of the most challenging complications that can occur following TJA, and as the number of primary and revision TJAs continues to rise, an increasing PJI burden is projected. Despite advances in operating room sterility, antiseptic protocols, and surgical techniques, approaches to prevent and treat PJI remain difficult, primarily due to the formation of microbial biofilms. This difficulty motivates researchers to continue searching for an effective antimicrobial strategy. The dextrorotatory-isoforms of amino acids (D-AAs) are essential components of peptidoglycan within the bacterial cell wall, providing strength and structural integrity in a diverse range of species. Among many tasks, D-AAs regulate cell morphology, spore germination, and bacterial survival, evasion, subversion, and adhesion in the host immune system. When administered exogenously, accumulating data have demonstrated that D-AAs play a pivotal role against bacterial adhesion to abiotic surfaces and subsequent biofilm formation; furthermore, D-AAs have substantial efficacy in promoting biofilm disassembly. This presents D-AAs as promising and novel targets for future therapeutic approaches. Despite their emerging antibacterial efficacy, their role in disrupting PJI biofilm formation, the disassembly of established TJA biofilm, and the host bone tissue response remains largely unexplored. This review aims to examine the role of D-AAs in the context of TJAs. Data to date suggest that D-AA bioengineering may serve as a promising future strategy in the prevention and treatment of PJI.

Improving disease prevention, diagnosis, and treatment using novel bionic technologies.

Increased human life expectancy, due in part to improvements in infant and childhood survival, more active lifestyles, in combination with higher patient expectations for better health outcomes, is leading to an extensive change in the number, type and manner in which health conditions are treated. Over the next decades as the global population rapidly progresses toward a super-aging society, meeting the long-term quality of care needs is forecast to present a major healthcare challenge. The goal is to ensure longer periods of good health, a sustained sense of well-being, with extended periods of activity, social engagement, and productivity. To accomplish these goals, multifunctionalized interfaces are an indispensable component of next generation medical technologies. The development of more sophisticated materials and devices as well as an improved understanding of human disease is forecast to revolutionize the diagnosis and treatment of conditions ranging from osteoarthritis to Alzheimer's disease and will impact disease prevention. This review examines emerging cutting-edge bionic materials, devices and technologies developed to advance disease prevention, and medical care and treatment in our elderly population including developments in smart bandages, cochlear implants, and the increasing role of artificial intelligence and nanorobotics in medicine.

Changes in interstitial fluid flow, mass transport and the bone cell response in microgravity and normogravity.

In recent years, our scientific interest in spaceflight has grown exponentially and resulted in a thriving area of research, with hundreds of astronauts spending months of their time in space. A recent shift toward pursuing territories farther afield, aiming at near-Earth asteroids, the Moon, and Mars combined with the anticipated availability of commercial flights to space in the near future, warrants continued understanding of the human physiological processes and response mechanisms when in this extreme environment. Acute skeletal loss, more severe than any bone loss seen on Earth, has significant implications for deep space exploration, and it remains elusive as to why there is such a magnitude of difference between bone loss on Earth and loss in microgravity. The removal of gravity eliminates a critical primary mechano-stimulus, and when combined with exposure to both galactic and solar cosmic radiation, healthy human tissue function can be negatively affected. An additional effect found in microgravity, and one with limited insight, involves changes in dynamic fluid flow. Fluids provide the most fundamental way to transport chemical and biochemical elements within our bodies and apply an essential mechano-stimulus to cells. Furthermore, the cell cytoplasm is not a simple liquid, and fluid transport phenomena together with viscoelastic deformation of the cytoskeleton play key roles in cell function. In microgravity, flow behavior changes drastically, and the impact on cells within the porous system of bone and the influence of an expanding level of adiposity are not well understood. This review explores the role of interstitial fluid motion and solute transport in porous bone under two different conditions: normogravity and microgravity.

Multi-functional cerium oxide nanoparticles regulate inflammation and enhance osteogenesis.

Oxidative stress increases bone loss and limits repair, in part, through immunoregulation and the formation and maintenance of low-grade chronic inflammation. The aim of this study was to investigate the effect of cerium oxide nanoparticles (CeONPs) on (i) macrophage phenotype and cytokine expression under normal and simulated acute and chronic inflammatory conditions and, (ii) human mesenchymal stem cell (hBMSCs) proliferation, osteoinduction and osteogenic differentiation. Spherical particles composed of 60% Ce3+ with a hydrodynamic size of ~35 nm and surface charge of 25.4 mV were internalized within cells. Under both acute and chronic conditions, inducible nitric oxide synthase (iNOS) activity decreased with a significant reduction seen in the 1 and 10 µg/mL groups (p < 0.001). A dose dependent and significant increase in anti-inflammatory cytokine gene expression was observed in all CeONP groups under chronic inflammatory condition. No increase in alkaline phosphatase (ALP) activity or mineral deposits were measured following hBMSCs cultured without osteogenic media in any of the CeONP groups, however, a significant increase in osteogenic-related gene expression, ALP activity and bone mineral deposits was measured when supplemented with both CeONPs and osteogenic media. CeONP activity was multifaceted and exhibited low toxicity. A therapeutic dose of 1 µg/mL delivered a disparate but protective effect when under both acute and chronic inflammatory conditions while at the same dose, potentiated osteogenesis.

Lactobacillus cell-free supernatant as a novel bioagent and biosurfactant against Pseudomonas aeruginosa in the prevention and treatment of orthopedic implant infection.

The hypothesis was that probiotic Lactobacillus species (spp.) or their cell-free supernatant (CFS) are effective in inhibiting (a) planktonic growth of Pseudomonas aeruginosa (PA), (b) its adhesion to a Ti6Al4V-alloy surface, and (c) in dispersing biofilm once formed. (a) A planktonic co-culture containing PA(104 colony-forming unit [CFU]/ml) was combined with either Lactobacillus acidophilus, Lactobacillus plantarum (LP), or Lactobacillus fermentum (LF) at a suspension of 104 (1:1) or 108 CFU/ml (1:2). Lactobacillus and PA CFUs were then quantified. (b) Ti-6Al-4V discs were inoculated with PA followed by supplementation with CFS and adherent PA quantified. (c) Biofilm covered discs were supplemented with Lactobacillus CFS and remaining PA activity quantified. Results showed that whole-cell cultures were ineffective in preventing PA growth; however, the addition of CFS resulted in a 99.99 ± 0.003% reduction in adherent PA in all Lactobacillus groups (p < .05 in all groups) with no viable PA growth measured in the LF and LP groups. Following PA biofilm formation, CFS resulted in a significant reduction in PA activity in all Lactobacillus groups (p ≤ .05 in all groups) with a 29.75 ± 15.98% increase measured in control samples. Supplementation with CFS demonstrated antiadhesive, antibiofilm, and toxic properties to PA.

Do polyunsaturated fatty acids protect against bone loss in our aging and osteoporotic population?

Age-related bone loss is inevitable in both men and women and there will soon be more people of extreme old age than ever before. Osteoporosis is a common chronic disease and as the proportion of older people, rate of obesity and the length of life increases, a rise in age-related degenerating bone diseases, disability, and prolonged dependency is projected. Fragility fractures are one of the most severe complications associated with both primary and secondary osteoporosis and current treatment strategies target weight-bearing exercise and pharmacological intervention, both with limited long-term success. Obesity and osteoporosis are intimately interrelated, and diet is a variable that plays a significant role in bone regeneration and repair. The Western Diet is characterized by its unhealthy components, specifically excess amounts of saturated fat intake. This review examines the impact of saturated and polyunsaturated fatty acid consumption on chronic inflammation, osteogenesis, bone architecture, and strength and explores the hypothesis that dietary polyunsaturated fats have a beneficial effect on osteogenesis, reducing bone loss by decreasing chronic inflammation, and activating bone resorption through key cellular and molecular mechanisms in our aging population. We conclude that aging, obesity and a diet high in saturated fatty acids significantly impairs bone regeneration and repair and that consumption of ω-3 polyunsaturated fatty acids is associated with significantly increased bone regeneration, improved microarchitecture and structural strength. However, ω-6 polyunsaturated fatty acids were typically pro-inflammatory and have been associated with an increased fracture risk. This review suggests a potential role for ω-3 fatty acids as a non-pharmacological dietary method of reducing bone loss in our aging population. We also conclude that contemporary amendments to the formal nutritional recommendations made by the Food and Nutrition Board may be necessary such that our aging population is directly considered.

The effect of strontium and silicon substituted hydroxyapatite electrochemical coatings on bone ingrowth and osseointegration of selective laser sintered porous metal implants.

Additive manufactured, porous bone implants have the potential to improve osseointegration and reduce failure rates of orthopaedic devices. Substantially porous implants are increasingly used in a number of orthopaedic applications. HA plasma spraying-a line of sight process-cannot coat the inner surfaces of substantially porous structures, whereas electrochemical deposition of calcium phosphate can fully coat the inner surfaces of porous implants for improved bioactivity, but the osseous response of different types of hydroxyapatite (HA) coatings with ionic substitutions has not been evaluated for implants in the same in vivo model. In this study, laser sintered Ti6Al4V implants with pore sizes of Ø 700 µm and Ø 1500 µm were electrochemically coated with HA, silicon-substituted HA (SiHA), and strontium-substituted HA (SrHA), and implanted in ovine femoral condylar defects. Implants were retrieved after 6 weeks and histological and histomorphometric evaluation were compared to electrochemically coated implants with uncoated and HA plasma sprayed controls. The HA, SiHA and SrHA coatings had Ca:P, Ca:(P+Si) and (Ca+Sr):P ratios of 1.53, 1.14 and 1.32 respectively. Electrochemically coated implants significantly promoted bone attachment to the implant surfaces of the inner pores and displayed improved osseointegration compared to uncoated scaffolds for both pore sizes (p<0.001), whereas bone ingrowth was restricted to the surface for HA plasma coated or uncoated implants. Electrochemically coated HA implants achieved the highest osseointegration, followed by SrHA coated implants, and both coatings exhibited significantly more bone growth than plasma sprayed groups (p≤0.01 for all 4 cases). SiHA had significantly more osseointegration when compared against the uncoated control, but no significant difference compared with other coatings. There was no significant difference in ingrowth or osseointegration between pore sizes, and the bone-implant-contact was significantly higher in the electrochemical HA than in SiHA or SrHA. These results suggest that osseointegration is insensitive to pore size, whereas surface modification through the presence of an osteoconductive coating plays an important role in improving osseointegration, which may be critically important for extensively porous implants.

Partial Bone Formation in Additive Manufactured Porous Implants Reduces Predicted Stress and Danger of Fatigue Failure.

New porous implant designs made possible by additive manufacturing allow for increased osseointegration, potentially improving implant performance and longevity for patients that require massive bone implants. The aim of this study was to evaluate how implantation and the strain distribution in the implant affect the pattern of bone ingrowth and how changes in tissue density within the pores alter the stresses in implants. The hypothesis was that porous metal implants are susceptible to fatigue failure, and that this reduces as osteointegration occurs. A phenomenological, finite element analysis (FEA) bone remodelling model was used to predict partial bone formation for two porous (pore sizes of 700 µm and 1500 µm), laser sintered Ti6Al4V implants in an ovine condylar defect model, and was compared and verified against in vivo, histology results. The FEA models predicted partial bone formation within the porous implants, but over-estimated the amount of bone-surface area compared to histology results. The stress and strain in the implant and adjacent tissues were assessed before, during bone remodelling, and at equilibrium. Results showed that partial bone formation improves the stress distribution locally by reducing stress concentrations for both pore sizes, by at least 20%. This improves the long-term fatigue resistance for the larger pore implant, as excessively high stress is reduced to safer levels (86% of fatigue strength) as bone forms. The stress distribution only changed slightly in regions without bone growth. As the extent of bone formation into extensively porous bone implants depends on the level of stress shielding, the design of the implant and stiffness have significant influence on bone integration and need to be considered carefully to ensure the safety of implants with substantial porous regions. To our knowledge this is the first time that the effect of bone formation on stress distribution within a porous implant has been described and characterised.

A novel ceramic coating for reduced metal ion release in metal-on-metal hip surgery.

An ovine total hip arthroplasty model was developed to evaluate metal ion release, wear, the biological response and adverse tissue reaction to metal-on-metal (MoM) bearing materials. The performance of an advanced superlattice ceramic coating (SLC) was evaluated as a bearing surface and experimental groups divided into; (1) MoM articulating surfaces coated with a SLC coating (SLC-MoM), (2) uncoated MoM surfaces (MoM), and (3) metal on polyethylene (MoP) surfaces. Implants remained in vivo for 13 months and blood chromium (Cr) and cobalt (Co) metal ion levels were measured pre and postoperatively. Synovial tissue was graded using an ALVAL scoring system. When compared with the MoM group, sheep with SLC-MoM implants showed significantly lower levels of chromium and cobalt metal ions within blood over the 13-month period. Evidence of gray tissue staining was observed in the synovium of implants in the MOM group. A significantly lower ALVAL score was measured in the SLC-MoM group (3.88) when compared with MoM components (6.67) (p = 0.010). ALVAL results showed no significant difference when SLC-MOM components were compared to MoP (5.25). This model was able to distinguish wear and the effect of released debris between different bearing combinations and demonstrated the effect of a SLC coating when applied onto the bearing surface. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1760-1771, 2019.

Novel adaptive finite element algorithms to predict bone ingrowth in additive manufactured porous implants.

Bone loss caused by stress shielding of metallic implants is a concern, as it can potentially lead to long-term implant failure. Surface coating and reducing structural stiffness of implants are two ways to improve bone ingrowth and osteointegration. Additive manufacturing, through selective laser sintering (SLS) or electron beam melting (EBM) of metallic alloys, can produce porous implants with bone ingrowth regions that enhance osteointegration and improve clinical outcomes. Histology of porous Ti6Al4V plugs of two pore sizes with and without electrochemically deposited hydroxyapatite coating, implanted in ovine condyles, showed that bone formation did not penetrate deep into the porous structure, whilst significantly increased bone growth along coated pore surfaces (osteointegration) was observed. Finite Element simulations, combining new algorithms to model bone ingrowth and the effect of surface modification on osteoconduction, were verified with the histology results. The results showed stress shielding of porous implants made from conventional titanium alloy due to material stiffness and implant geometry, limiting ingrowth and osteointegration. Simulations for reduced implant material stiffness predicted increased bone ingrowth. For low modulus Titanium-tantalum alloy (Ti-70%Ta), reduced stress shielding and enhanced bone ingrowth into the porous implant was found, leading to improved mechanical interlock. Algorithms predicted osteoconductive coating to promote both osteointegration and bone ingrowth into the inner pores when they were coated. These new Finite Element algorithms show that using implant materials with lower elastic modulus, osteoconductive coatings or improved implant design could lead to increased bone remodelling that optimises tissue regeneration, fulfilling the potential of enhanced porosity and complex implant designs made possible by additive layer manufacturing techniques.

A novel adaptive algorithm for 3D finite element analysis to model extracortical bone growth.

Extracortical bone growth with osseointegration of bone onto the shaft of massive bone tumour implants is an important clinical outcome for long-term implant survival. A new computational algorithm combining geometrical shape changes and bone adaptation in 3D Finite Element simulations has been developed, using a soft tissue envelope mesh, a novel concept of osteoconnectivity, and bone remodelling theory. The effects of varying the initial tissue density, spatial influence function and time step were investigated. The methodology demonstrated good correspondence to radiological results for a segmental prosthesis.

The effect of bone growth onto massive prostheses collars in protecting the implant from fracture.

Limb-sparing distal femoral endoprotheses used in cancer patients have a high risk of aseptic loosening. It had been reported that young adolescent patients have a higher rate of loosening and fatigue fracture of intramedullary stems because the implant becomes undersized as patients grow. Extracortical bone growth into the grooved hydroxyapatite-coated collar had been shown to reduce failure rates. The stresses in the implant and femur have been calculated from Finite Element models for different stages of bone growth onto the collar. For a small diameter stem without any bone growth, a large stress concentration at the implant shoulder was found, leading to a significant fracture risk under normal walking loads. Bone growth and osseointergration onto the implant collar reduced the stress level in the implant to safe levels. For small bone bridges a risk of bone fracture was observed.

Controlled laser texturing of titanium results in reliable osteointegration.

We have developed a laser-textured superhydrophilic Ti-6Al-4V surface with unique surface chemistry and topography that substantially promotes osteoblast adhesion in culture. Here we investigate the osteointegration of laser-textured implants in an ovine model. Our hypothesis was that laser-textured implants, without any surface coating (LT), would encourage comparable amounts of bone-implant contact and interfacial strength when compared with widely accepted hydroxyapatite (HA) coated implants. Additionally, we hypothesized that LT would significantly increase bony integration compared with machine-finished (MF) and grit-blasted (GB) implants. Forty-eight tapered transcortical pins were implanted into six sheep. Four experimental groups (LT, HA, MF, and GB) were investigated (n = 12) and implants remained in vivo for 6 weeks. Bone apposition rates, interfacial shear strength, and bone-implant contact (BIC) were quantified. The interfacial strength of LT and HA implants were found to be significantly greater than GB (p = 0.032 and p = 0.004) and MF (p = 0.004 and p = 0.004, respectively), but no significant difference between LT and HA implants was observed. Significantly increased BIC was measured adjacent to HA implants when compared with both LT and GB implant surfaces (p = 0.022 and p = 0.006, respectively). No significant difference was found when LT and GB implants were compared. However, all surface finishes encouraged significantly increased BIC when compared with the MF surface. Maximizing implant fixation to host bone is vital for its long-term success. The production of an LT surface is a simple and cheap manufacturing process and this study demonstrated that laser-textured implants are a very promising technical development that warrants further research. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:820-828, 2017.