Ti-6Al-4V is the most common alloy used for orthopaedic implants. Its popularity is due to low density, superior corrosion resistance, good osseointegration and lower elastic modulus when compared to other commonly used alloys such as CoCrMo and stainless steel. In fact, the use of Ti64 has even further increased lately since recent controversy around adverse local tissue reactions and implant failure related to taper corrosion of CoCrMo alloy. However, implants made from Ti64 can fail in some cases due to fatigue fracture, sometimes related to oxide induced stress corrosion cracking or hydrogen embrittlement, or preferential corrosion of the beta phase. Studies performed with Ti-6Al-4V do often not consider that the alloy itself may have a range of characteristics that can vary and could significantly impact the implant properties. These variations are related to the material microstructure which depends not only on chemical composition, but also the manufacturing process and subsequent heat treatments. Different microstructures can occur in implants made form wrought alloys, cast alloys, and more recently, additive manufactured (AM) alloys. Implant alloy microstructure drives mechanical and electrochemical properties. Therefore, this study aims to analyse the microstructure of Ti-6Al-4V alloy of additive manufactured and conventional retrieved orthopaedic implants such as acetabular cups, tibial trays, femoral stem and modular neck by means of electron backscatter diffraction (EBSD). Microstructural features of interest include grains shape and size, phase content and distribution, preferred grain orientation (texture), alloying elements distribution (homogenization) and presence of impurities. Additionally, we demonstrate the direct impact of different microstructural features on hardness. We analysed 17 conventional devices from 6 different manufacturers, 3 additive manufactured devices from 2 different manufactures and 1 control alloy (bar stock). The preliminary results showed that even though all implants have the same chemical composition, their microstructural characteristics vary broadly. Ti64 microstructure of conventional alloys could be categorized in 3 groups: equiaxed grains alloys (Fine and Coarse), bimodal alloys and dendritic alloys. The additive manufactured implants were classified in an additional group on its own which consists of a needle-like microstructures - similar to Widmanstätten patterns, Fig. 1, with a network of β phase along α phase grains. Furthermore, AM alloys exhibited residual grain boundaries from the original β grains from the early stage of the solidification process, Fig. 2. These characteristics may have implication on the fatigue and corrosion behaviour. In addition, it we observed inhomogeneous alloying element distribution in some cases, Fig. 3, especially for the additive manufactured alloys, which also may have consequences on corrosion behaviour. Finally, the hardness testing revealed that the implants with large grain size, such as AM alloys, exhibit low hardness values, as expected, but also the amount of beta phase correlated positively with lower hardness. Grain aspect ratio and beta phase grain size correlated positively with higher hardness. In summary, we found that common Ti64 implants can exhibit a broad variety of different alloy microstructures and the advent of AM alloys introduces an entirely new category. It is imperative to determine the ideal microstructure for specific applications

Background. Additive manufacturing (AM) has created many new avenues for material and manufacturing innovation. In orthopaedics, metal additive manufacturing is now widely used for production of joint replacements, spinal fusion devices, and cranial maxillofacial reconstruction. Plastic additive manufacturing on the other hand, has mostly been utilized for pre-surgical planning models and surgical cutting guides. The addition of pharmaceuticals to additively manufactured plastics is novel, particularly when done at the raw material level. The purpose of this study was to prove the concept of antibiotic elution from additively manufactured polymeric articles and demonstrate feasibility of application in orthopaedics. Methods. Using patented processes, three heat-stable antibiotics commonly used in orthopaedics were combined with six biocompatible polymers (2 bioresorbable) into filament and powder base materials for fused deposition modeling (FDM) and selective laser sintering (SLS) AM processes. Raw materials of 1%, 2%, and 5% antibiotic concentrations (by mass) were produced as well as a blend of all three antibiotics each at 1% concentration. Thin disks of 25 mm diameter were manufactured of each polymer with each antibiotic at all concentrations. Disks were applied to the center of circular petri dishes inoculated with a bacterium as per a standard zone of inhibition, or Kirby-Bauer disk diffusion tests. After 72 hours incubation, the zone of inhibited bacterial growth was measured. Periprosthetic joint infection (PJI) of the knee was selected as the proof-of-concept application in orthopaedics. A series of tibial inserts mimicking those of a common TKR system were manufactured via SLS using a bioresorbable base material (Figure 1). Three prototype inserts were tested on a knee wear simulator for 333,000 cycles following ISO 14242–1:2014 to approximate 2–4 months of in vivo use between surgeries of a 2-stage procedure for PJI. Gravimetric measurement and visual damage assessment was performed. Results. Bacterial growth was inhibited to a mean diameter of 32.3 mm (FDM) and 42.2 mm (SLS) for nearly all combinations of polymers and concentrations of antibiotics. Prototype tibial inserts experienced an average of 200 mg of wear during testing and demonstrated no evidence of cracking, delamination or significant deformation (Figure 2). Conclusion. Bench-level testing of these novel antibiotic-eluting polymers demonstrates feasibility for their application in orthopaedic medicine. In particular, treatment of stubborn PJI with potential for increased and sustained antibiotic elution, patient-specific cocktailing, and maintenance of knee joint structure and function compared to existing PJI products and practices. Subsequent testing for these novel polymers will determine static and dynamic (wear-induced) antibiotic elution rates. For any figures or tables, please contact the authors directly

Implant loosening is one of the primary mechanisms of failure for hip, knee, ankle and shoulder arthroplasty. Many established implant fixation surfaces exist to achieve implant stability and fixation. More recently, additive manufacturing technology has offered exciting new possibilities for implant design such as large, open, porous structures that could encourage bony ingrowth into the implant and improve long-term implant fixation. Indeed, many implant manufacturers are exploiting this technology for their latest hip or knee arthroplasty implants. The purpose of this research is to investigate if the design freedoms offered by additive manufacturing could also be used to improve initial implant stability – a precursor to successful long-term fixation. This would enable fixation equivalent to current technology, but with lower profile fixation features, thus being less invasive, bone conserving and easier to revise. 250 cylindrical specimens with different fixation features were built in Ti6Al4V alloy using a Renishaw AM250 additive manufacturing machine, along with 14 specimens with a surface roughness similar to a conventional titanium fixation surface. Pegs were then pushed into interference fit holes in a synthetic bone material using a dual-axis materials testing machine equipped with a load/torque-cell (figure 1). Specimens were then either pulled-out of the bone, or rotated about their cylindrical axis before being pulled out to quantify their ability to influence initial implant stability. It was found that additively manufactured fixation features could favourably influence push-in/pull-out stability in one of two-ways: firstly the fixation features could be used to increase the amount pull-out force required to remove the peg from the bone. It was found that the optimum fixation feature for maximising pull-out load required a pull-out load of 320 N which was 6× greater than the least optimum design (54 N) and nearly 3× the maximum achieved with the conventional surface (120 N). Secondly, fixation features could also be used to decrease the amount of force required to insert the implant into bone whilst improving fixation (figure 2). Indeed, for some designs the ratio of push-in to pull-out was as high as 2.5, which is a dramatic improvement on current fixation surface technology, which typically achieved a ratio between 0.3–0.6 depending on the level of interference fit. It was also found that the additively manufactured fixation features could influence the level of rotational stability with the optimum design resisting 3× more rotational torque compared to the least optimum design. It is concluded that additive manufacturing technology could be used to improve initial implant stability either by increasing the anchoring force in bone, or by reducing the force required to insert an implant whilst maintaining a fixed level of fixation. This defines a new set of rules for implant fixation using smaller low profile features, which are required for minimally invasive device design

Introduction. The number of total hip arthroplasties has been increasing worldwide, and it is expected that revision surgeries will increase significantly in the near future. Although reconstructing normal hip biomechanics with extensive bone loss in the revision surgery remains challenging. The custom−made acetabular component produced by additive manufacturing, which can be fitted to a patient's anatomy and bone defect, is expected to be a predominant reconstruction material. However, there have been few reports on the setting precision and molding precision of this type of material. The purpose of this study was to validate the custom−made acetabular component regarding postoperative three−dimensional positioning and alignment. Methods. Severe bone defects (Paprosky type 3A and 3B) were made in both four fresh cadaveric hip joints using an acetabular reamer mimicking clinical cases of acetabular component loosening or osteolysis in total hip arthroplasty. On the basis of computed tomography (CT) after making the bone defect, two types of custom−made acetabular components (augmented type and tri−flanged type) that adapted to the bone defect substantially were produced by an additive manufacturing machine. A confirmative CT scan was taken after implantation of the component, and then the data were installed in an analysis workstation to compare the postoperative component position and angle to those in the preoperative planning. Results. The mean absolute deviations of the center of the hip joint between preoperative planning and the actual component position in the augmented type were 0.7 ± 0.4 mm for the horizontal position, 0.2 ± 0.1 mm for the vertical position, and 0.5 ± 0.3 mm for the antero−posterior position. The mean absolute deviations of the center of the hip joint in the tri−flanged type in the horizontal, vertical, and antero−posterior positions were 1.0 ± 0.4 mm, 0.4 ± 0.2 mm, 0.3 ± 0.1 mm, respectively. The mean absolute deviations of the component angle were 3.5° ± 0.9° at inclination and 2.0° ± 1.7° at anteversion in the augmented type and 0.6° ± 0.5° at inclination and 0.9° ± 0.3° at anteversion in the tri−flanged type. Conclusion. Since custom−made orthopaedic implants produced by additive manufacturing can support individual anatomy and bone defect, this type of implant is expected to be applied to revision surgery and bone tumor surgery for severe bone defects. The present study demonstrated that preoperative planning of the center of the hip joint was successfully reproduced after the implantation of both types of custom−made acetabular components. In the tri−flanged type, better satisfactory results were provided in the component position and angle by comparing the past CAOS tools such as a surgical navigation system and a patient−specific guide. There is scope for further improvement, but the custom−made acetabular component produced by additive manufacturing may become very useful reconstruction material in hip revision surgeries. Problems to be addressed in the future include the improvement of the reproducibility of the preoperative planning and investigation of long−term clinical results

Surface coatings have been introduced to total joint orthopaedics over the past decades to enhance osseointegration between metal implants and bone. However, complications such as aseptic loosening and infection persist. Inadequate osseointegration remains a complication associated with implants that rely on osseointegration for proper function. This is particularly challenging with implants having relatively flat and small surface areas that have high shear loading, such as noncemented uni and total condylar knee tibial trays. Faster osseointegration can enhance recovery as a result of improved load distribution and a more stable bone-implant interface. Traditionally noncemented porous bone ingrowth coatings on knee, hip and shoulder implants are typically texturised by thermal plasma spray coating, sintered metal bead coatings, or 3-D additive manufactured structures that provide porous surface features having the rough texture with pore sizes on the order of 150 to 300 micrometers. These surfaces are often further chemically enhanced with hydroxyapatite (HA) deposition. This provides macro-mechanical (millimeter scale) and micro-mechanical (micrometer scale) bone remodeling into the implant surface. However, at the nanoscale and cellular level, these surfaces appear relatively smooth. More recent studies are showing the importance of controlling the macro, micro, and the nano (nanometer scale) surface topographies to enhance cell interaction. In vitro and in vivo research shows surfaces with nanoscale features in the metal substrate result in enhanced osseointegration, greater bone-implant contact area and pullout force, and potentially bactericidal. One surface modification treatment technique of particular promise is nano-texturing via electrochemical anodization to bio-mimicking TiO2 nanotube arrays that are superimposed onto existing porous surface microstructures to further enhance the already known bone ingrowth properties of these porous structures by superimposing onto the existing microstructure arrays of nanotubes approximately 100 nanometers in outside diameter and 300–500 nanometers in height. In an ovine model, 3-D printed Direct Metal Laser Deposition (DMLS) additive manufactured porous Ti-6Al-4V implant with and without TiO2 nanotube array nano-texturing were compared to similar sized implants with commercially available sintered beads with HA coating and additive manufactured cobalt chrome implants. The average bond strength was significantly higher (42%) when the implants were nano-texturised and similarly stronger (53%) compared to HA coated sintered bead implants. Histology confirms over 420% more direct bonded growth of new bone from 0.5mm to 1.0mm deep into the porosity on the implants when the same implants are nano-texturised. Nano-texturing also changes the surface of the implant to repel methicillin-resistant staphylococcus aureus (MRSA) in an in vivo rabbit model limiting biofilm formation on the porous surface compared with non-treated porous surfaces. Since nano-texturizing only modifies the nano-morphology of the surface and does not add antibiotics or other materials to the implant, these animal studies shows great promise that nano-texturizing the TiO2 coating may not only enhance osseointegration, but also repels bacteria from porous implant surfaces. As such, we believe nano-texturing of porous implants will be the next advancement in surface coating technology

Porous surfaces on orthopaedic implants have been shown to promote tissue ingrowth. This study evaluated biological fixation of novel additively manufactured porous implants with and without hydroxyapatite coatings in a canine transcortical model. Laser rapid manufacturing (LRM) Ti6Al4V cylindrical implants were built with a random interconnected architecture mimicking cancellous bone (5.2 mm diameter, 10mm length, 50–60% porous, mean pore size 450μm). Three groups were investigated in this study: as-built with no coating (LRM), as-built coated with solution precipitated hydroxyapatite (LRM-PA), and as-built coated with a plasma sprayed hydroxyapatite (LRM-PSHA). Implants were press-fit into a 5mm unicortical, perpendicular drill hole in the femoral diaphysis of the left and right femurs in 12 canines. Right femora were harvested for histology (SEM, bone ingrowth into implant within cortical region) and left femora for mechanical push-out testing (shear strength of bone-implant interface) at 4 and 12 weeks (N=6, un-paired Student's t-test, p=0.05). For mean bone ingrowth, there was no significant difference between groups at 4 weeks (LRM, LRM-PA, LRM-PSHA: 41.5+8.6%, 51+5.5% and 53.2+11%, respectively) or 12 weeks (LRM, LRM-PA, LRM-PSHA: 64.4+2.8%, 59.9+7.6%, 64.9+6.4%, respectively). LRM and LRM-PA implants had more bone ingrowth at 12 weeks than 4 weeks (p < 0 .05). Mean shear strength of all implants at 12 weeks (LRM, LRM-PA, LRM-PSHA: 39.9+3.6MPa, 33.7+4.6MPa, 36+4.1MPa respectively) were greater than at 4 weeks (LRM, LRM-PA, LRM-PSHA: 21.6+2.8MPa, 20.7+1.1MPa, 20.2+2.5MPa respectively) (p < 0 .05). No significant difference was observed between all groups at 4 or 12 weeks. Overall, this canine study confirmed the suitability of this novel additive manufacturing porous material for biological fixation by bone ingrowth. All implants exhibited high bone ingrowth and mechanical shear strength in this canine model. No difference was observed between uncoated and hydroxyapatite coated implants

We present the indications and outcomes of a series of custom 3D printed titanium acetabular implants used over a 9 year period at our institution (Sydney, Australia), in the setting of revision total hip arthroplasty. Individualised image-based case planning with additive manufacturing of pelvic components was combined with screw fixation and off-the-shelf femoral components to treat patients presenting with failed hip arthroplasty involving acetabular bone loss. Retrospective chart review was performed on the practices of three contributing surgeons, with an initial search by item number of the Medicare Benefits Scheme linked to a case list maintained by the manufacturer. An analysis of indications, patient demographics and clinical outcome was performed. The cohort comprised 65.2% female with a median age of 70 years (interquartile range 61–77) and a median follow up of 32.9 months (IQR 13.1 - 49.7). The indications for surgery were infection (12.5%); aseptic loosening (78.1%) and fracture (9.4%), with 65.7% of cases undergoing previous revision hip arthroplasty. A tumour prosthesis was implanted into the proximal femur in 21.9% of cases. Complications were observed in 31.3% of cases, with four cases requiring revision procedures and no deaths reported in this series. Kaplan-Meier analysis of all-cause revision revealed an overall procedure survival of 88.7% at two years (95%confidence interval 69 - 96.2) and 83.8% (95%CI 62 - 93.7) at five years, with pelvic implant-specific survival of 98% (95%CI 86.6 - 99.7) at two and five year follow up. We conclude that an individualised planning approach for custom 3D printed titanium acetabular implants can provide high overall and implant-specific survival at up to five years follow up in complex cases of failed hip arthroplasty and acetabular bone loss

Background. It is known that severe cases of intervertebral disc (IVD) disease may lead to the loss of natural intervertebral height, which can cause radiating pain throughout the lower back and legs. To this point, surgeons perform lumbar fusion using interbody cages, posterior instrumentation and bone graft to fuse adjacent vertebrae together, thus restoring the intervertebral height and alleviating the pain. However, this surgical procedure greatly decreases the range of motion (ROM) of the treated segment, mainly caused by high cage stiffness. Additive manufacturing can be an interesting tool to reduce the cage's elastic modulus (E), by adding porosity (P) in its design. A porous cage may lead to an improved osteointegration since there is more volume in which bone can grow. This work aims to develop a finite element model (FEM) of the L4-L5 functional spinal unit (FSU) and investigate the loss of ROM induced by solid and porous cages. Materials and Methods. The Intact-FEM of L4-L5 was created, which considered the vertebrae, IVD and ligaments with their respective material properties. 1. The model was validated by comparing its ROM with that of other studies. Moments of 10 Nm were applied on top of L4 while the bottom of L5 was fixed to simulate flexion, extension, lateral bending and axial rotation. 2. The lumbar cages, posterior instrumentation and bone graft were then modelled to create the Cage-FEMs. Titanium was chosen for the instrumentation and cages. Cages with different stiffness were considered to represent porous structures. The solid cage had the highest modulus (E. 0. =110 GPa, P. 0. =0%) whereas the porous cages were simulated by lowering the modulus (E. 1. =32.8 GPa, P. 1. =55%; E. 2. =13.9 GPa, P. 2. =76%; E. 3. =5.52 GPa, P. 3. =89%; E. 4. =0.604 GPa, P. 4. =98%), following the literature. 3. The IVD was removed in Cage-FEMs to allow the implant's insertion [Fig. 1] and the previous loading scenarios were simulated to assess the effects of cage porosity on ROM. Results. The Intact-FEM presents acceptable ROM according to experimental and numerical studies, as shown by the red line in Figure 2. After insertion, lower ROM values in Cage-FEMs are measured for each physiological movement [Fig. 3]. In addition, highly porous cages have greater ROM, especially in axial rotation. Discussion. Significant reduction of ROM is expected after cage insertion because the main goal of interbody fusion is to allow bone growth. As such, the procedure's success is highly dependent on segmental stability, which is achieved by using cages in combination with bone graft and posterior instrumentation. Furthermore, higher cage porosities seem to affect the FSU. In fact, ROM increases more as the cage modulus approaches that of the cancellous bone (E. canc-bone. =0.2 GPa. 1. ). Next step will be to assess the effects of cage design on the L4-L5 FSU mechanical behavior and stress distribution. To conclude, additive manufacturing offers promising possibilities regarding implant optimization, being able to create porous cages, thus reducing their stiffness. For any figures or tables, please contact the authors directly

Introduction. Integrating additively manufactured structures, such as porous lattices into implants has numerous potential benefits, such as custom mechanical properties, porosity for osseointegration/fluid flow as well as improved fixation features. Component anisotropic stiffness can be controlled through varying density and lattice orientation. This is useful due to the influence of load on bone remodelling. Matching implant and bone anisotropy/stiffness may help reduce problems such as stress shielding and prevent implant loosening. It is therefore beneficial to be able to design AM parts with a desired anisotropic stiffness. In this study we present a method that predicts the anisotropic stiffness of an additively manufactured lattice structure from its CAD data, and validate this model with experimental testing. The model predicts anisotropic stiffness in terms of density (ρ), fabric (M) and fabric eigen values (m) and is matched to stiffness data of the structure in 3 principal directions, based on an orthotropic assumption. This model was described in terms of 10 constants and had the form shown in Equation 1. Eq.1. S. =. ∑. i. ,. j. =. 1.  .  .  .  . i. ,. j. =. 3. λ. (. i. ,. j. ). ρ. k. m. (. i. ). 1. (. i. ). m. (. j. ). 1. (. i. ). |. M. i. M. j. '. |. 2. Methods. A stochastic line structure was formed in CAD by joining pseudo-random points generated using the Poisson-disk method Lines at an angle lower than 30° to the x-y plane removed to allow for AM manufacturing. Lines were converted to struts with 330 µm diameter. Second order fabric tensors were determined from CAD files of the AM specimens using the mean intercept length (MIL), the gold standard for determining a measure of the ‘average orientation’ of material within trabecular bone structures. 10 × 10 × 12 mm specimens of the CAD model were manufactured on a Renishaw AM250 powder bed fusion machine. The structure was built in 10 different orientations to enable stiffness measurement in 10 different directions (n=5 for each direction). Compression testing in a servohydraulic materials testing machine was performed according to ISO13314 with LVDTs used to measure displacement to remove compliance effects. Stress-strain curves were obtained and elastic moduli were estimated from a hysteresis loop in the load application, from 70% to 20% of the plateau stress. Specimen density and fabric data were fit to the observed stiffnesses using least squares linear regression. Experimental stiffnesses of the structure in 10 directions were compared to the model to evaluate the accuracy of model predictions. Results & Discussion. The model predicted the stiffness of the structure across all 10 orientations to within 13% absolute error compared to the observed stiffness data, with an R. 2. value of 0.969. The three dimensional stiffness plot formed by the model was similar to the experimental data, displaying an hourglass shape. Our model is the first to predict the anisotropic stiffness of stochastic structures and will be highly useful in predicting stiffness of lattice structures and could also be applied to bone to measure anisotropic stiffness. For any figures or tables, please contact authors directly

Aseptic loosening is the most common cause of failure in load bearing orthopaedic implants. This is most often attributed to stress shielding, which is caused by a mismatch in mechanical properties between the implant and bone, predominantly stiffness. The implant causes a redistribution of the forces through the bone leading to localised tissue resorption in low stress areas and over time loosening of the implant. To address this, the implant design may be modified to introduce porous structures that reduced overall stiffness. Conventional methods of creating porous structures include the space holder method and gas foaming, although these allow control of the pore size and volume fraction, the position of the voids is random and potentially non-uniform, creating unpredictable mechanical properties. Using additive manufacture predictable porous lattice structures can be built. Two methods for creating lattice structure are explored here: controlled stochastic lattices, and layers of repeating unit cells. Due to the predictable nature of these design methods the mechanical properties can be tailored to suit the needs of the implants. In addition to mechanical optimisation the porous lattice structures can be optimised for osseointegration properties. The ability of the tissue to grow into the implant are affected by; the size of the pores, how interconnected the pores are, the overall void fraction (porosity), the shape and roughness of the pores, and whether the structure is coated. Although additive manufacture allows great design freedoms, there are also some manufacturing constraints to consider including resolution which is determined by powder and laser spot size, and strut angle since these cannot be too close to horizontal or they will collapse during the build unless supported. This preliminary work uses Finite Element Analysis to model the compressive properties of lattice structures with different design parameters, with the intention to optimise for mechanical, osseointegration and manufacturability properties. Cylinders of the lattice structures were generated in Simpleware ScanIP (Synopsys, Exeter, UK) and their compression was modelled in Ansys Workbench 18.2 (Canonsburg, PA, USA) in accordance with ISO 13314. Stress distributions for each lattice structure were produced which showed the stochastic lattice did not undergo banded deformation unlike the repeating unit cell based lattices. Future work will physically test the lattices and feed that data back into the model for further optimisation. Other relevant mechanical testing will be modelled and performed in order to choose the optimal lattice design for future implants

Recent clinical data suggest improvement in the fixation of tibia trays for total knee arthroplasty when the trays are additive manufactured with highly porous bone ingrowth structures. Currently, press-fit TKA is less common than press-fit THA. This is partly because the loads on the relatively flat, porous, bony apposition area of a tibial tray are more demanding than those same porous materials surrounding a hip stem. Even the most advanced additive manufactured (AM) highly porous structures have bone ingrowth limitations clinically as aseptic loosening still remains more common in press-fit TKA vs. THA implants. Osseointegration and antibacterial properties have been shown in vitro and in vivo to improve when implants have modified surfaces that have biomimetic nanostructures designed to mimic and interact with biological structures on the nano-scale. Pre-clinical evaluations show that TiO. 2. nanotubes (TNT), produced by anodization, on Ti6Al4V surfaces positively enhance the rate at which osseointegration occurs and TNT nano-texturization enhances the antibacterial properties of the implant surface. 2. In this in vivo sheep study, identical Direct Metal laser Sintered (DMLS) highly porous Ti6Al4V specimens with and without TNT surface treatment are compared to sintered bead specimens with plasma sprayed hydroxyapatite-coated surface treatment. Identical DMLS specimens made from CoCrMo were also implanted in sheep tibia bi-cortically (3 per tibia) and in the cancellous bone of the distal femur and proximal tibia (1 per site). Animals were injected with fluorochrome labels at weeks 1, 2 and 3 after surgery to assess the rate of bone integration. The cortical specimens were mechanically tested and processed for PMMA histology and histomorphometry after 4 or 12 weeks. The cancellous samples were also processed for PMMA histology and histomorphometry. The three types of bone labels were visualized under UV light to examine the rate of new bony integration. At 4 weeks, a 42% increase in average pull-out shear strength between nanotube treated specimens and non-nanotube treated specimens was shown. A 21% increase in average pull-out shear strength between nanotube treated specimens and hydroxyapatite-coated specimens was shown. At 12 weeks, all specimens had statistically similar pull-out values. Bone labels demonstrated new bone formation into the porous domains on the materials as early as 2 weeks. A separate in vivo study on 8 rabbits infected with methicillin-resistant Staphylococcus aureus showed bacterial colonization reduction on the surface of the implants treated with TNT. In vitro and in vivo evidence suggests that nanoscale surfaces have an antibacterial effect due to surface energy changes that reduce the ability of bacteria to adhere. These in vivo studies show that TNT on highly porous AM specimens made from Ti6Al4V enhances new bone integration and also reduce microbial attachment

Introduction. New challenges arise in total hip arthroplasty (THA) as patients are younger and perform higher levels of activity. Implants need to stand increased loads, last longer and improve bone stock conservation. [1]. for future revision. Additive manufacturing allows optimizing the implant shape and material properties imposing few restrictions. The mechanical properties of porous meta-materials can be adjusted by tailoring their meso-structure, allowing for a functional gradation of the material properties (i.e. elastic modulus) throughout the stem. The objective of this paper is to use finite element analysis for optimizing the shape and the functional gradation of material properties distribution of hip stems in order to reduce the bone loss and to obtain lower and more homogeneous interfacial stresses. Methods. The 2D stem geometry (initially Profemur. ®. TL) was parameterized with 8 variables. Limits were established to keep tapered stem shape, avoid intersecting the cortexes and assure proper cortical contact. A functional gradation of the stem's material properties was generated by prescribing the values of the elastic modulus (E) on a 53 points grid. Values for E were between 2 GPa (highly porous meta-material made of Ti6Al4V) and 110 GPa (solid Ti6Al4V). The stem neck and a 1.5 mm layer around the stem were kept solid. Two contradictory objective functions were considered: 1) a function of the total bone loss, accounting for the bone losses due to the resection for the implant insertion and due to stress shielding; 2) a function of the interfacial shear stresses, accounting for their uniformity and value. This multi-objective optimization problem was solved using genetic algorithms for stair climbing load case. [2]. , with 30090 stem design evaluations for a total of 50 generations (iterations). Two representative optimized stem designs were selected to undergo a second step of tailoring their porous meta-material for obtaining the desired material properties distribution. Simple-cubic unit cell was considered at the mesoscale of the porous meta-material, with a fixed unit-cell length of 1.5 mm. The strut diameter at each point of the grid was optimized to match the prescribed E using a previously developed model of porous meta-materials that includes the manufacturing irregularities. [3]. . Results. Fig.1 shows FBLFIS functions for the optimized stem designs at the last generation. For optimized stems FBL=21.5–26.6% and FIS=0.27–3.64; for the original stem design FBL=35.4% and FIS=10.20. Optimized stems are shorter, thinner and less stiff than the original stem design; and they show smaller extent of bone resorption and smaller and more homogeneous interfacial shear stresses (Fig.2). The E distribution is adequately reproduced by the porous material (Fig.2). Conclusion. Combining shape and material properties distribution optimization of hip stems can improve their mechanical compatibility with the bone, reducing the bone loss and interfacial shear stresses. The material properties distribution can be adequately obtained by tailoring additively manufactured porous meta-materials. This is expected to improve the THA long-term outcome and the conditions for future revision. For figures/tables, please contact authors directly.

Orthopaedic reconstruction procedures to combat osteoarthritis, inflammatory arthritis, metabolic bone disease and other musculoskeletal disorders have increased dramatically, resulting in high demand on the advancement of bone implant technology. In the past, joint replacement operations were commonly performed primarily on elderly patients, in view of the prosthesis survivorship. With the advances in surgical techniques and prosthesis technology, younger patients are undergoing surgeries for both local tissue defects and joint replacements. This patient group is now more active and functionally more demanding after surgery. Today, implanted prostheses need to be more durable (load-bearing), they need to better match the patient's original biomechanics and be able to survive longer. Additive manufacturing (AM) provides new possibilities to further combat the problem of stress-shielding and promote better bone remodelling/ingrowth and thus long term fixation. This can be accomplished by matching the varying strain response (stiffness) of trabecular or subchondral bone locally at joints. The purpose of this research is therefore to determine whether a porous structure can be produced that can match the required behaviour and properties of trabecular bone regardless of skeletal location and can it be incorporated into a long-term implant. A stochastic structure visually similar to trabecular bone was designed and optimised for AM (Figure 1) and produced over a range of porosities in multiple materials, Stainless Steel 316, Titanium (Grade 23 – Ti6Al4V ELI) and Commercially Pure Titanium (Grade 2) using a Renishaw AM250 metal additive manufacturing system. Over 150 cylindrical specimens were produced per material and subjected to a compression test to determine the specimens' Elastic Modulus (Stiffness) and Compressive Yield Strength. Micro-CT scans and gravimetric analysis were also performed to determine and validate the specimens' porosity. Results were then graphed on a Strength vs. Stiffness Ashby plot (Figure 2) comparing the values to those of trabecular bone in the tibia and femur. It was found that AM can produce porous structures with an elastic modulus as low as 100 MPa up to 2.7 GPa (the highest stiffness investigated in this study). Titanium structures with a stiffness <500MPa had compressive strengths towards the bottom range of similar stiffness trabecular bone. Between 500 MPa − 1 GPa Titanium AM porous structures match the compressive strength of equivalent stiffness trabecular bone and from 1 GPa − 2 GPa the Ti structures exceed the strength of equivalent stiffness trabecular bone up to ∼2.5 times and consequently increase by a power law. These results show that AM can produce structures with similar stiffness to trabecular bone over a range of skeletal locations whilst matching or exceeding the compressive strength of bone. The results have not yet taken into account fatigue life with the fatigue life of these types of structures tending to be between 0.1 – 0.4 of their compressive strength. This means that a titanium porous structure would need to be 2.5 – 10 times stiffer or stronger than the portion of trabecular bone it is replacing. This data is highly encouraging for AM manufactured, bone stiffness matched implant technology

OSSTEC is a pre-spin-out venture at Imperial College London seeking industry feedback on our orthopaedic implants which maintain bone quality in the long term. Existing orthopaedic implants provide successful treatment for knee osteoarthritis, however, they cause loss of bone quality over time, leading to more dangerous and expensive revision surgeries and high implant failure rates in young patients. OSSTEC tibial implants stimulate healthy bone growth allowing simple primary revision surgery which will provide value for all stakeholders. This could allow existing orthopaedics manufacturers to capture high growth in existing and emerging markets while offering hospitals and surgeons a safer revision treatment for patients and a 35% annual saving on lifetime costs. For patients, our implant technology could mean additional years of quality life by revising patients to a primary TKA before full revision surgery. Our implants use patent-filed additive manufacturing technology to restore a healthy mechanical environment in the proximal tibia; stimulating long term bone growth. Proven benefits of this technology include increased bone formation and osseointegration, shown in an animal model, and restoration of native load transfer, shown in a human cadaveric model. This technology could help capture the large annual growth (24%) currently seen in the cementless knee reconstruction market, worth $1.2B. Furthermore, analysis suggests an additional market of currently untreated younger patients exists, worth £0.8B and growing by 18% annually. Making revision surgery and therefore treatment of younger patients easier would enable access to this market. We aim to offer improved patient treatment via B2B sales of implants to existing orthopaedic manufacturer partners, who would then provide them with instrumentation to hospitals and surgeons. Existing implant materials provide good options for patient treatments, however OSSTEC's porous titanium structures offer unique competitive advantages; combining options for modular design, cementless fixation, initial bone fixation and crucially long term bone maintenance. Speaking to surgeons across global markets shows that many surgeons are keen to pursue bone preserving surgeries and the use of porous implants. Furthermore, there is a growing demand to treat young patients (with 25% growth in patients younger than 65 over the past 10 years) and to use cementless knee treatments, where patient volume has doubled in the past 4 years and is following trends in hip treatments. Our team includes engineers and consultant surgeons who have experience developing multiple orthopaedic implants which have treated over 200,000 patients. To date we have raised £175,000 for the research and development of these implants and we hope to gain insight from industry professionals before further development towards our aim to begin trials for regulatory approval in 2026. OSSTEC implants provide a way to stimulate bone growth after surgery to reduce revision risk. We hope this could allow orthopaedic manufactures to explore high growth markets while meaning surgeons can treat younger patients in a cost effective way and add quality years to patients' lives

The treatment of critical-sized bone defects still remains today a challenge, especially when the surrounding soft, vascularized and innervated tissues have been damaged - a lack of revascularization within the injured site leading to physiological disorders, from delayed healing to osteonecrosis. The axial insertion of a vascular bundle (e.g. arterio-venous loop, AVL) within a synthetic bone filler to initiate and promote its revascularization has been foreseen as a promising alternative to the current strategies (e.g., vascularized free flaps) for the regeneration of large bone defects. In a previous work, we showed that the insertion of a vein in a 3D-printed monetite scaffold induced its higher revascularization than AVL, thus a possible simplification of the surgical procedures (no microsurgery required). Going further, we investigate in this study whether or not the presence of a vein could stimulate the formation of mineralized tissue insides a synthetic scaffold filled with bone marrow and implanted in ectopic site. Monetite scaffolds were produced by additive manufacturing according to a reactive 3D-printing technique co-developed by the authors then thoroughly characterized. Animal study was performed on 14 male Wistar rats. After anesthesia and analgesia, a skin medial incision in rat thigh allowed the site on implantation to be exposed. Bone marrow was collected on the opposite femur through a minimally invasive procedure and the implant was soaked with it. For the control group (N=7), the implant was inserted in the incision and the wound was closed whereas the femoral bundle was dissected and the vein inserted in the implant for the experimental group (N=7). After 8 weeks animals were sacrificed, the implant collected and fixed in a 4% paraformaldehyde solution. Explants were characterized by µCT then embedded in poly-methyl methacrylate prior SEM, histology and immunohistochemistry. Images were analyzed with CT-Analyzer (Bruker) and ImageJ (NIH) and statistical analyses were carried out using SPSS (IBM). Implants were successfully 3D-printed with a +150 µm deviation from the initial CAD. As expected, implants were composed of 63%wt monetite and 37%wt unreacted TCP, with a total porosity of 44%. Data suggested that scaffold biodegradation was significantly higher when perfused by a vein. Moreover, the latter allowed for the development of a dense vascular network within the implant, which is far more advanced than for the control group. Finally, although mineralized tissues were observed both inside and outside the implant for both groups, bone formation appeared to be much more important in the experimental one. The ectopic formation of a new mineralized tissue within a monetite implant soaked with bone marrow seems to be highly stimulated by the simple presence of a vein alone. Although AVL have been studied extensively, little is known about the couple angiogenesis/osteogenesis which appears to be a key factor for the regeneration of critical-sized bone defects. Even less is known about the mechanisms that lead to the formation of a new bone tissue, induced by the presence of a vein only. With this in mind, this study could be considered as a proof of concept for further investigations

This paper describes how advances in three-dimensional printing may benefit the military trauma patient, both deployed on operations and in the firm base. Use of rapid prototype manufacturing to produce a 3D representation of complex fractures that can be held and rotated will aid surgical planning within multidisciplinary teams. Patient-clinician interaction can also be aided using these graspable models. The education of military surgeons could improve with the subsequent accurate, inexpensive models for anatomy and surgical technique instruction. The developing sphere of additive manufacturing (3D printing functional end-use components) lends itself to further advantages for the military orthopaedic surgeon. Military trauma patients could benefit from advances in direct metal laser sintering which enable the manufacture of complex surfaces and porous structures on bio-metallic implants not possible using conventional manufacturing. “Bio-printing” of tissues mimicking anatomical structures has potential for military trauma patients with bone defects. Deployed surgeons operating on less familiar fracture sites could benefit from three-dimensionally printing patient-specific medical devices. These can make operating technically easier, reducing radiation exposure and operating time. Further ahead, it may be possible to contemporaneously 3D print medical devices unavailable from the logistics chain whilst operating in the deployed environment

Biodegradable metals as orthopaedic implant materials receive substantial scientific and clinical interest. Marketed cardiovascular products confirm good biocompatibility of iron. Solid iron biodegrades slowly in vivo and has got supra-physiological mechanical properties as compared to bone and porous implants can be optimized for specific orthopaedic applications. We used Direct Metal Printing (DMP)3 to additively manufacture (AM) scaffolds of pure iron with fine-tuned bone-mimetic mechanical properties and improved degradation behavior to characterize their biocompatibility under static and dynamic 3D culture conditions using a spectrum of different cell types. Atomized iron powder was used to manufacture scaffolds with a repetitive diamond unit cell design on a ProX DMP 320 (Layerwise/3D Systems, Belgium). Mechanical characterization (Instron machine with a 10kN load cell, ISO 13314: 2011), degradation behavior under static and dynamic conditions (37ºC, 5% CO2 and 20% O2) for up of 28 days, with μCT as well as SEM/energy-dispersive X-ray spectroscopy (EDS) (SEM, JSM-IT100, JEOL) monitoring under in vivo-like conditions. Biocompatibility was comprehensively evaluated using a broader spectrum of human cells according to ISO 10993 guidelines, with topographically identical titanium (Ti-6Al-4V, Ti64) specimen as reference. Cytotoxicity was analyzed by two-way ANOVA and post-hoc Tukey's multiple comparisons test (α = 0.05). By μCT, as-built strut size (420 ± 4 μm) and porosity of 64% ± 0.2% were compared to design values (400 μm and 67%, respectively). After 28 days of biodegradation scaffolds showed a 3.1% weight reduction after cleaning, while pH-values of simulated body fluids (r-SBF) increased from 7.4 to 7.8. Mechanical properties of scaffolds (E = 1600–1800 MPa) were still within the range for trabecular bone, then. At all tested time points, close to 100% biocompatibility was shown with identically designed titanium (Ti64) controls (level 0 cytotoxicity). Iron scaffolds revealed a similar cytotoxicity with L929 cells throughout the study, but MG-63 or HUVEC cells revealed a reduced viability of 75% and 60%, respectively, already after 24h and a further decreased survival rate of 50% and 35% after 72h. Static and dynamic cultures revealed different and cell type-specific cytotoxicity profiles. Quantitative assays were confirmed by semi-quantitative cell staining in direct contact to iron and morphological differences were evident in comparison to Ti64 controls. This first report confirms that DMP allows accurate control of interconnectivity and topology of iron scaffold structures. While microstructure and chemical composition influence degradation behavior - so does topology and environmental in vitro conditions during degradation. While porous magnesium corrodes too fast to keep pace with bone remodeling rates, our porous and micro-structured design just holds tremendous potential to optimize the degradation speed of iron for application-specific orthopaedic implants. Surprisingly, the biological evaluation of pure iron scaffolds appears to largely depend on the culture model and cell type. Pure iron may not yet be an ideal surface for osteoblast- or endothelial-like cells in static cultures. We are currently studying appropriate coatings and in vivo-like dynamic culture systems to better predict in vivo biocompatibility

Introduction. Stress shielding of bone around the stem components of total shoulder replacement (TSR) implants can result in bone resorption, leading to loosening and failure. Titanium is an ideal biomaterial for implant stems; however, it is much stiffer than bone. Recent advances in additive manufacturing (AM) have enabled the production of parts with complex geometries from titanium alloys, such as hollow or porous stems. The objective of this computational study is to determine if hollow titanium stems can reduce stress shielding at the proximal humerus. We hypothesize that hollow TSR implant stems will reduce stress shielding in comparison with solid stems and the inner wall thickness of the hollow stem will be a design parameter with a direct effect on bone stresses. Methods. Using a previously developed statistical shape and density model (SSDM) of the humerus based on 75 cadaveric shoulders, a simulated average CT image was created. Using MITK-GEM, the cortical and trabecular bones were segmented from this CT image and meshed with quadratic tetrahedral elements. Trabecular bone was modeled as an isotropic and inhomogeneous material, with the Young's modulus defined element-by-element based on the corresponding CT densities. Cortical bone was assumed isotropic with a uniform Young's modulus of 20 GPa. The Poisson's ratio for all bone was 0.3. The distal humerus was fully constrained. Bone stresses were calculated by performing finite element analyses in ABAQUS with a 320 N force and 2 Nm frictional moment applied to the articular surface of the humeral head, based on an in vivo study during 45 degrees of shoulder abduction. Subsequently, the humeral head was resected and reamed to receive solid- and hollow-stemmed implants with identical external geometries but three different inner wall thicknesses (Figure 1). The identical surrounding bone meshes for the intact and reconstructed bones allowed element-by-element stress comparisons. The volume-weighted average changes in cortical and trabecular bone von Mises stresses were calculated, (wrt the intact humerus), as well as the percentage of bone volume experiencing a relative increase or decrease in stress greater than 10%. Results. Results for all four implant designs are summarized (Figure 2). The solid stem resulted in the biggest average change in von Mises stresses (4% decrease in cortical and 6% increase in cancellous bone stress). The solid stem also resulted in the largest volume of bone experiencing a decrease in stress. Comparing the hollow stems, the thinnest shell wall resulted in the smallest changes in cortical bone stress, and the lowest volumes of bone experiencing a decrease in stress. Interestingly, this design caused the most cancellous bone to experience an increase in stress. Discussion. These results suggest a marginal improvement in the bone-implant mechanics of hollow versus solid stems, and that thinner shell walls perform better. That said, the improvements over the solid stem design are minimal. Further increasing the compliance of these stems, e.g. by adding pores, may improve their performance. Future work will focus on optimizing hollow and porous stem designs, and the possibility of leveraging their hollow design for drug delivery. For any figures or tables, please contact the authors directly

Introduction. Patient Specific Guides (PSGs) are used to increase the accuracy of arthroplasty. PSGs achieve this by incorporating geometry that fits in one unique position and orientation on a patient's bone. Sufficient docking rigidity ensures PSGs do not shift before being fixed by pins. Despite the importance of PSG docking rigidity, minimal research has been conducted on this issue. This study aims to determine whether commercially available PSGs, in their equilibrium position, provide sufficient stability for reliable surgical use. Materials and Methods. A commercially available PSG (Glenoid PSG, BLUEPRINT™, Wright Medical) was analyzed and tested in this study; the mechanical performance of this guide was assessed using a custom testing apparatus mounted to a universal testing machine (UTM) (MTI-10k, Materials Testing Inc), assembled with a high-precision load cell (MiniDyn Type 9256C, Kistler). The apparatus accepts an additively manufactured glenoid surrogate and was designed to transform vertical crosshead forces from the UTM into PSG-applied forces transverse to the glenoid plane along anterior-posterior and superior-inferior axes and PSG-applied torques about lateral, anterior, and superior axes. Three trials were recorded for each force and torque application. Prior to each test, the glenoid surrogate and PSG were articulated together with a constant 27N compressive force — equivalent to the normal force exerted by a surgeon using the guide — applied using springs. Forces were recorded when the guide was displaced 2mm by transverse loads or 5° by torque application; if the guide visibly dislodged from the glenoid surrogate before either criterion was met, force was recorded at the time of dislodgement. If no PSG movement occurred, testing ceased at 75N or 1.19N⋅m, depending on the test type. Results. The lowest and highest torques to displace the PSG by 5° were around the lateral (−0.08±0.02 N⋅m) and superior axes (0.87±0.23 N⋅m), respectively. The lowest and highest forces to displace the PSG by 2mm were along the inferior (31.77± 6.30N) and posterior axes (64.80±0.79N), respectively. Although it yielded at a higher torque than about the lateral axis, CCW rotation about the posterior axis produced the earliest PSG dislodgement at 3.76° while the PSG dislodged after only 1.05mm in the anterior direction. Discussion. The above results demonstrate that the tested PSG design produces similar docking rigidity for all tested rotations except rotations about the lateral axis, which provided 4 times less stability than the next lowest result. This indicates that the PSG may not provide sufficient resistance in this direction to prevent inadvertent mal-rotation. The relatively low rigidity in anterior and superior translation indicate that this PSG design may be prone to mal-positioning errors in these directions. With these data in mind, PSG docking rigidity is not equal in all loading directions which could play a role in the clinical accuracy. Furthermore, this indicates that a systematic, objective method for PSG design optimization may be warranted. For any figures or tables, please contact authors directly

Introduction. Long term data on the survivorship of cemented total knee arthroplasty (TKA) has demonstrated excellent outcomes; however, with younger, more active patients, surgeons have a renewed interest in improved biologic fixation obtained from highly porous, cementless implants. Early designs of cementless total knees systems were fraught with high rates of failure for aseptic loosening, particularly on the tibial component. Prior studies have assessed the bone ingrowth extent for tibial tray designs reporting near 30% extent of bone ingrowth . (1,2). While these analyses were performed on implants that demonstrated unacceptably high rates of clinical failure, a paucity of data exists on the extent on bone ingrowth in contemporary implant designs with newer methods for manufacturing the porous surfaces. We sought to evaluate the extent of attached bone on retrieved cementless tibial trays to determine if patient demographics, device factors, or radiographic results correlate to the extent of bone ingrowth in these contemporary designs. Methods. Using our IRB approved retrieval database, 17 porous tibial trays were identified and separated into groups based on manufacturer: Zimmer Natural Knee (1), Zimmer NexGen (10), Stryker Triathlon (4) and Biomet Vanguard Regenerex (2). Differences in manufacturing methods for porous material designs were recorded. Patient demographics and reason for revision are described in Table 1. Radiographs were used to measure tibiofemoral alignment and the tibial mechanical axis alignment. Components were assessed using visual light microscopy and Photoshop to map bone ingrowth extent across the porous surface. ImageJ was used to threshold and calculate values for bone, scratched metal, and available surface for bone ingrowth (Fig. 1). Percent extent was determined as the bone ingrowth compared to the surface area excluding any scratched regions from explantation. Statistics were performed among tray designs as well as between the lateral and medial pegs, if designs had pegs available for bony ingrowth. Results. Mean bone ingrowth extent was 51.4% for the tibial tray for the entire cohort. Bone ingrowth extent was statistically greater in the Zimmer NexGen design (63.8%; p=.027) compared to the other three designs (Table 2). Four sets of pegs were excluded from analysis due to lack of porous coatings or pegs having been removed at revision surgery. Across all designs, the medial peg had 45.2% ingrowth and the lateral peg had 66.1% ingrowth. The medial peg for the NexGen design had significantly less bone ingrowth compared to the lateral peg (58.7% vs. 75.4%; p=0.044). No significant differences were found in tibiofemoral alignment or tibial mechanical axis alignment between the implant groups. No significant differences were found among implants revised for aseptic loosening versus any other reason for revision (54% vs 30%; p=.18). Discussion. Our results demonstrate high rates of bone ingrowth extent in contemporary designs, further supporting porous design rationales and a role for additive manufacturing to form enhanced porosity. We plan on exploring staining techniques to confirm our visual inspection. Contemporary designs have shown successful rates for improved longevity for cementless total knee systems. For any figures or tables, please contact the authors directly