The rational design of bone-substituting biomaterials is relatively complex because they should meet a long list of requirements for optimal performance. Meta-biomaterials are micro-architected materials that hold great promise for meeting those requirements as they offer a unique combination of mechanical, mass-transport, and biological properties. There are, however, inherent couplings between the different types of properties of many such materials that make it impossible to simultaneously achieve all the design criteria. An example of such a coupling exists between the mechanical properties and the surface area. Strut-based, metallic meta-biomaterials are known to offer bone-mimicking mechanical properties, but they have limited surface area for cell adherence. Increasing the surface generally results in an undesirable increase in the mechanical properties that could lead to stress shielding. Here, we combine strut-based lattices with minimal surfaces to decouple these two properties. We added minimal surface patches to the designs of both auxetic and non-auxetic meta-biomaterials while minimizing their contribution to the mechanical properties of the resulting meta-biomaterials through the rational application of cuts or “slits”. All designs were additively manufactured using selective laser melting and mechanically tested to obtain their quasi-static mechanical properties, including their Poisson's ratio, in two configurations. A finite element-based computational homogenization code was used to compute the elastic moduli and anisotropy of the structures. The results show that the minimal surface patches substantially increase the available surface area without significantly affecting the mechanical properties. Without the slits, the surfaces significantly affected the elastic modulus and deformation behavior of the meta-biomaterials. A similar strategy could be used to tune the biodegradation rate of biodegradable metals and the permeability of meta-biomaterials in general.@en

Orthopedic plates are commonly used after osteotomies for temporary fixation of bones. Patient-specific plates have recently emerged as a promising fixation device. However, it is unclear how various strategies used for the design of such plates perform in comparison with each other. Here, we compare the biomechanical performance of 3D printed patient-specific bone plates designed using conventional computer-aided design (CAD) techniques with those designed with the help of topology optimization (TO) algorithms, focusing on cases involving slipped capital femoral epiphysis (SCFE). We established a biomechanical testing protocol to experimentally assess the performance of the designed plates while measuring the full-field strain using digital image correlation. We also created an experimentally validated finite element model to analyze the performance of the plates under physiologically relevant loading conditions. The results indicated that the TO construct exhibited higher ultimate load and biomechanical performance as compared to the CAD construct, suggesting that TO is a viable approach for the design of such patient-specific bone plates. The TO plate also distributed stress more evenly over the screws, likely resulting in more durable constructs and improved anatomical conformity while reducing the risk of screw and plate failure during cyclic loading. Although differences existed between finite element analysis and experimental testing, this study demonstrated that finite element modelling can be used as a reliable method for evaluating and optimizing plates for SCFE patients. In addition to enhancing the mechanical performance of patient-specific fixation plates, the utilization of TO in plate design may also improve the surgical outcome and decrease the recovery time by reducing the plate and incision sizes.@en

Objective: Mandibular reconstruction using patient-specific cage implants is a promising alternative to the vascularized free flap reconstruction for nonirradiated patients with adequate soft tissues, or for patients whose clinical condition is not conducive to microsurgical reconstruction. This study aimed to assess the biomechanical performance of 3D printed patient-specific cage implants designed with a semi-automated workflow in a combined cadaveric and retrospective case series study. Methods: We designed cage implants for two human cadaveric mandibles using our previously developed design workflow. The biomechanical performance of the implants was assessed with the finite element analysis (FEA) and quasi-static biomechanical testing. Digital image correlation (DIC) was used to measure the full-field strains and validate the FE models by comparing the distribution of maximum principal strains within the bone. The retrospective study of a case series involved three patients, each of whom was treated with a cage implant of similar design. The biomechanical performance of these implants was evaluated using the experimentally validated FEA under the scenarios of both mandibular union and nonunion. Results: No implant or screw failure was observed prior to contralateral bone fracture during the quasi-static testing of both cadaveric mandibles. The FEA and DIC strain contour plots indicated a strong linear correlation (r = 0.92) and a low standard error (SE=29.32με), with computational models yielding higher strain values by a factor of 2.7. The overall stresses acting on the case series’ implants stayed well below the yield strength of additively manufactured (AM) commercially pure titanium, when simulated under highly strenuous chewing conditions. Simulating a full union between the graft and remnant mandible yielded a substantial reduction (72.7±1.5%) in local peak stresses within the implants as compared to a non-bonded graft. Conclusions: This study shows the suitability of the developed semi-automated workflow in designing patient-specific cage implants with satisfactory mechanical functioning under demanding chewing conditions. The proposed workflow can aid clinical engineers in creating reconstruction systems and streamlining pre-surgical planning. Nevertheless, more research is still needed to evaluate the osteogenic potential of bone graft insertions.@en

Implant-associated infections are highly challenging to treat, particularly with the emergence of multidrug-resistant microbials. Effective preventive action is desired to be at the implant site. Surface biofunctionalization of implants through Ag-doping has demonstrated potent antibacterial results. However, it may adversely affect bone regeneration at high doses. Benefiting from the potential synergistic effects, combining Ag with other antibacterial agents can substantially decrease the required Ag concentration. To date, no study has been performed on immobilizing both Ag and Fe nanoparticles (NPs) on the surface of additively manufactured porous titanium. We additively manufactured porous titanium and biofunctionalized its surface with plasma electrolytic oxidation using a Ca/P-based electrolyte containing Fe NPs, Ag NPs, and the combinations. The specimen’s surface morphology featured porous TiO2 bearing Ag and Fe NPs. During immersion, Ag and Fe ions were released for up to 28 days. Antibacterial assays against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa showed that the specimens containing Ag NPs and Ag/Fe NPs exhibit bactericidal activity. The Ag and Fe NPs worked synergistically, even when Ag was reduced by up to three times. The biofunctionalized scaffold reduced Ag and Fe NPs, improving preosteoblasts proliferation and Ca-sensing receptor activation. In conclusion, surface biofunctionalization of porous titanium with Ag and Fe NPs is a promising strategy to prevent implant-associated infections and allow bone regeneration and, therefore, should be developed for clinical application.@en

Additive manufacturing technologies in general and laser powder bed fusion (L-PBF) in particular have been on the rise in different applications, including biomedical implants. The effects of the various L-PBF process parameters on the microstructure and properties of Ti6Al4V lattice structures have been studied before. However, the relationship between the different modes of laser scanning and the resulting microstructure, internal imperfections, and surface morphology is still underexplored. In this study, the aforementioned parameters and their effect on the compressive mechanical properties and fatigue behaviour of lattice titanium have been studied for both continuous and pulsed laser scanning modes. Moreover, the influence of various combinations of post-processing treatments, such as hot isostatic pressing (HIP), sandblasting, and chemical etching, on the quasi-static mechanical properties and fatigue endurance of the resulting materials were investigated. It was found that continuous laser strategy results in fewer imperfections and higher fatigue resistance, while pulsed laser showed a more homogenous microstructure; likely leading to a more isotropic behaviour. Furthermore, the continuous mode showed larger prior β grains preferentially oriented in the building direction, while pulsed specimens exhibited finer equiaxed grains with no preferred orientations. The highest level of fatigue life was obtained by using an optimized combination of HIP, sandblasting, and chemical etching.@en

Additively manufactured (AM) porous structures are a new class of biomaterials with many advantages as compared to conventionally produced biomaterials. The goal of this study was to find out how the laser processing parameters including laser power and exposure time affect the mechanical properties, topology, and microstructure of porous biomaterials AM using a novel vector-based approach. Several cylindrical porous specimens were additively manufactured using a wide range of exposure time and laser power. The effects of those parameters on the surface roughness, strut diameter, relative density, hardness, elastic modulus, yield stress, first maximum stress, and plateau stress of the porous structures were studied. The results showed that the rate of change in mechanical and topological properties with respect to exposure time was non-linear while it was linear with respect to the laser power. The results also showed that the effects of laser power and exposure time on the mechanical properties and topology of AM porous structures could be decoupled from each other, enabling derivation of predictive emperical relationships. The emperical and experimental curves showed very good agreement, which further validates the validity of the separation method used for obtaining the emperical relationships. The analytical relationships for elastic modulus and yield stress that we had obtained in a previous study could predict the elastic modulus and yield stress of the porous strucutres when the energy input was high enough (i.e. exposure times ≥ 450 μs), because the local mechanical properties of the matrix material decreased for the lower levels of energy input. The change in the mechanical properties of the bulk material due to change in laser processing parameters should thus be taken into account.@en

Recently, lattice titanium manufactured by additive manufacturing (AM) techniques has been utilized in various applications, including biomedical. The effects of topological design and processing parameters on the fatigue behaviour of such meta-biomaterials have been studied before. Most studies show that the fatigue life of additively manufactured lattice structures is limited. Post-processing techniques could play a major role in improving the fatigue of these promising biomaterials. This study aims to provide an in-depth investigation into the effects of heat treatments, hot isostatic pressing (HIP), sand blasting, and chemical etching on the microstructure, surface morphology, strength and fatigue resistance of selective laser melted titanium meta-biomaterials. It was found that the combination of microstructural design and surface engineering, induced by HIP and sand blasting respectively, allows to increase the endurance limit of these lattice meta-biomaterials by a factor of two. HIP treatment substantially decreased the internal porosity and transformed the microstructure to a more ductile mixture of α + β phases. Sand blasting allowed to eliminate surface imperfections and induced favourable compressive stress in the surface layer of the struts. Statement of Significance: Additively manufactured metallic meta-biomaterials are progressively being used as bone replacement orthopedic implants. While there is a great amount of research related to topological designs and their effect on mechanical (e.g. stiffness), physical (e.g. mass transport), and biological (e.g. osseointegration) properties, fatigue lifetime of such structures remains limited. This study provides fundamental investigation into the combined effect of microstructural design and surface engineering of titanium meta-biomaterial, enabled through various post treatment methods ranging from heat treatments to physical and chemical surface modifications. The findings show that fatigue life is significantly improved by applying developed herein novel method, which effortlessly can be used on other bone-mimicking metallic meta-biomaterials.@en

Recently, lattice titanium manufactured by additive manufacturing (AM) techniques has been utilized in various applications, including biomedical. The effects of topological design and processing parameters on the fatigue behaviour of such meta-biomaterials have been studied before. Most studies show that the fatigue life of additively manufactured lattice structures is limited. Post-processing techniques could play a major role in improving the fatigue of these promising biomaterials. This study aims to provide an in-depth investigation into the effects of heat treatments, hot isostatic pressing (HIP), sand blasting, and chemical etching on the microstructure, surface morphology, strength and fatigue resistance of selective laser melted titanium meta-biomaterials. It was found that the combination of microstructural design and surface engineering, induced by HIP and sand blasting respectively, allows to increase the endurance limit of these lattice meta-biomaterials by a factor of two. HIP treatment substantially decreased the internal porosity and transformed the microstructure to a more ductile mixture of α + β phases. Sand blasting allowed to eliminate surface imperfections and induced favourable compressive stress in the surface layer of the struts. Statement of Significance: Additively manufactured metallic meta-biomaterials are progressively being used as bone replacement orthopedic implants. While there is a great amount of research related to topological designs and their effect on mechanical (e.g. stiffness), physical (e.g. mass transport), and biological (e.g. osseointegration) properties, fatigue lifetime of such structures remains limited. This study provides fundamental investigation into the combined effect of microstructural design and surface engineering of titanium meta-biomaterial, enabled through various post treatment methods ranging from heat treatments to physical and chemical surface modifications. The findings show that fatigue life is significantly improved by applying developed herein novel method, which effortlessly can be used on other bone-mimicking metallic meta-biomaterials.@en

BACKGROUND: Anterior glenohumeral instability with >20% glenoid bone loss is a disorder that can be treated with the Latarjet stabilizing procedure; however, complications are common. The purposes of this study were to (1) evaluate the effect of an anatomic-specific titanium implant produced by 3-dimensional (3D) printing as a treatment option for recurrent shoulder instability with substantial glenoid bone loss and (2) compare the use of that implant with the Latarjet procedure. METHODS: Ten fresh-frozen cadaveric shoulders (mean age at the time of death, 78 years) were tested in a biomechanical setup with the humerus in 30° of abduction and in neutral rotation. The shoulders were tested under 5 different conditions: (1) normal situation, (2) creation of an anterior glenoid defect, (3) implantation of an anatomic-specific titanium implant produced by 3D printing, and the Latarjet procedure (4) with and (5) without 10 N of load attached to the conjoined tendon. In each condition, the humerus was translated 10 mm anteriorly relative to the glenoid, and the maximum peak translational force that was necessary for this translation was measured. RESULTS: After creation of the glenoid defect, the mean translational peak force decreased by 30% ± 6% compared with that for the normal shoulder. After restoration of the original glenoid anatomy, the translational force needed to dislocate the humeral head from the glenoid significantly increased compared with that in the defect condition-to 119% ± 16% of normal (p < 0.01) with the 3D-printed anatomic-specific implant and to 121% ± 48% of normal (p < 0.01) following the Latarjet procedure. No significant differences in mean translational force were found between the anatomic-specific implant and the Latarjet procedure (p = 0.72). CONCLUSIONS: The mean translational peak force needed to dislocate the humerus 10 mm anteriorly on the glenoid was higher after glenoid restoration with the 3D-printed anatomic-specific implant compared with when the glenoid had a 20% surface defect but also compared with when the glenoid was intact. No differences in mean translational peak force were found between the 3D-printed anatomic-specific glenoid implant and the Latarjet procedure, although there was less variability in the 3D-implant condition. CLINICAL RELEVANCE: Novel 3D-printing technology could provide a reliable patient-specific alternative to solve problems related to traditional treatment methods for shoulder instability.@en

The treatment of femoral nonunion with large segmental bone defect is still challenging. Although magnesium alloys have been considered potential materials for such a treatment, their application is limited by their fast degradation. Adding bioceramic particles into magnesium to form Mg-matrix composites is a promising strategy to adjust their biodegradation rates and to improve their mechanical properties and cytocompatibility further. Here, we developed an extrusion-based additive manufacturing technique to fabricate biodegradable Mg-Zn/bioceramic composite scaffolds ex-situ. Inks carrying a Mg-Zn powder and 5, 10 and 15% β-tricalcium phosphate (TCP) powder particles were investigated regarding the dispersion of β-TCP particles in the inks and viscoelastic properties. Optimally formulated inks were then employed for subsequent 3D printing of porous composite scaffolds. The in vitro biodegradation rate of the scaffolds containing 5% β-TCP decreased to 0.5 mm/y, which falls within the range desired for critical-sized bone substitution. As compared to the monolithic Mg-Zn scaffolds, the elastic moduli and yield strengths of the composite scaffolds were much enhanced, which remained in the range of the cancellous bone properties even after 28 d of in vitro degradation. The Mg-Zn/5TCP and Mg-Zn/10TCP scaffolds also exhibited improved biocompatibility when cultured with preosteoblasts, as compared to Mg-Zn scaffolds. In addition, the ALP activity and mineralization level of the composite scaffolds were much enhanced in the extracts of the composite scaffolds. Taken together, this research marks a great breakthrough in fabricating porous Mg-matrix composite scaffolds that meet several design criteria in terms of appropriate biodegradation rate, mechanical properties, and bioactivity. Statement of significance: The treatment of posttraumatic femoral nonunion with large segmental bone defect is still challenging. In this study, we developed a multi-material extrusion-based additive technique to fabricate porous Mg/bioceramic composite scaffolds for such a treatment. The technique allowed for the fine-tuning of printable inks to optimize the dispersion of micro-sized particles. The relative densities of the struts of the fabricated composite scaffolds reached 99%. The added bioceramic particles (β-TCP) exhibited proper interfacial bonding with the Mg alloy matrix. The porous Mg-based composite possessed desired biodegradability, bone-mimicking mechanical properties throughout the in vitro biodegradation period and improved bioactivity to bone cells. These results demonstrated great prospects of extrusion-based 3D printed porous Mg materials to be developed further as ideal biodegradable bone-substituting materials.@en

Advanced additive manufacturing techniques have been recently used to tackle the two fundamental challenges of biodegradable Fe-based bone-substituting materials, namely low rate of biodegradation and insufficient bioactivity. While additively manufactured porous iron has been somewhat successful in addressing the first challenge, the limited bioactivity of these biomaterials hinder their progress towards clinical application. Herein, we used extrusion-based 3D printing for additive manufacturing of iron-matrix composites containing silicate-based bioceramic particles (akermanite), thereby addressing both of the abovementioned challenges. We developed inks that carried iron and 5, 10, 15, or 20 vol% of akermanite powder mixtures for the 3D printing process and optimized the debinding and sintering steps to produce geometrically-ordered iron-akermanite composites with an open porosity of 69–71%. The composite scaffolds preserved the designed geometry and the original α-Fe and akermanite phases. The in vitro biodegradation rates of the composites were improved as much as 2.6 times the biodegradation rate of geometrically identical pure iron. The yield strengths and elastic moduli of the scaffolds remained within the range of the mechanical properties of the cancellous bone, even after 28 days of biodegradation. The composite scaffolds (10–20 vol% akermanite) demonstrated improved MC3T3-E1 cell adhesion and higher levels of cell proliferation. The cellular secretion of collagen type-1 and the alkaline phosphatase activity on the composite scaffolds (10–20 vol% akermanite) were, respectively higher than and comparable to Ti6Al4V in osteogenic medium. Taken together, these results clearly show the potential of 3D printed porous iron-akermanite composites for further development as promising bone substitutes. Statement of significance: Porous iron matrix composites containing akermanite particles were produced by means of multi-material additive manufacturing to address the two fundamental challenges associated with biodegradable iron-based biomaterials, namely very low rate of biodegradation and insufficient bioactivity. Our porous iron-akermanite composites exhibited enhanced biodegradability and superior bioactivity compared to porous monolithic iron scaffolds. The murine bone cells proliferated on the composite scaffolds, and secreted the collagen type-1 matrix that stimulated bony-like mineralization. The results show the exceptional potential of the developed porous iron-based composite scaffolds for application as bone substitutes.@en

Background: The primary aim of this study was to determine and compare the biomechanical properties of a fractured or intact rib after implant fixation on an embalmed thorax. Methods: Five systems were fixated on the bilateral fractured or intact (randomly allocated) 6th to 10th rib of five post-mortem embalmed human specimens. Each rib underwent a four-point bending test to determine the bending structural stiffness (Newton per m2), load to failure (Newton), failure mode, and the relative difference in bending structural stiffness and load to failure as compared to a non-fixated intact rib. Findings: As compared to a non-fixated intact rib, the relative difference in stiffness of a fixated intact rib ranged from −0.14 (standard deviation [SD], 0.10) to 0.53 (SD 0.35) and for a fixated fractured rib from −0.88 (SD 0.08) to 0.17 (SD 0.50). The most common failure mode was a new fracture at the most anterior drill hole for the plate and screw systems and a new fracture within the anterior portion of the implant for the clamping systems. Interpretation: The current fixation systems differ in their design, mode of action, and biomechanical properties. Differences in biomechanical properties such as stiffness and load to failure especially apply to fractured ribs. Insight in the differences between the systems might guide more specific implant selection and increase the surgeon's awareness for localizing hardware complaints or failure.@en

The development of biodegradable Fe-based bone implants has rapidly progressed in recent years. Most of the challenges encountered in developing such implants have been tackled individually or in combination using additive manufacturing technologies. Yet not all the challenges have been overcome. Herein, we present porous FeMn-akermanite composite scaffolds fabricated by extrusion-based 3D printing to address the unmet clinical needs associated with Fe-based biomaterials for bone regeneration, including low biodegradation rate, MRI-incompatibility, mechanical properties, and limited bioactivity. In this research, we developed inks containing Fe, 35 wt% Mn, and 20 or 30 vol% akermanite powder mixtures. 3D printing was optimized together with the debinding and sintering steps to obtain scaffolds with interconnected porosity of 69%. The Fe-matrix in the composites contained the γ-FeMn phase as well as nesosilicate phases. The former made the composites paramagnetic and, thus, MRI-friendly. The in vitro biodegradation rates of the composites with 20 and 30 vol% akermanite were respectively 0.24 and 0.27 mm/y, falling within the ideal range of biodegradation rates for bone substitution. The yield strengths of the porous composites stayed within the range of the values of the trabecular bone, despite in vitro biodegradation for 28 d. All the composite scaffolds favored the adhesion, proliferation, and osteogenic differentiation of preosteoblasts, as revealed by Runx2 assay. Moreover, osteopontin was detected in the extracellular matrix of cells on the scaffolds. Altogether, these results demonstrate the remarkable potential of these composites in fulfilling the requirements of porous biodegradable bone substitutes, motivating future in vivo research. Statement of significance: We developed FeMn-akermanite composite scaffolds by taking advantage of the multi-material capacity of extrusion-based 3D printing. Our results demonstrated that the FeMn-akermanite scaffolds showed an exceptional performance in fulfilling all the requirements for bone substitution in vitro, i.e., a sufficient biodegradation rate, having mechanical properties in the range of trabecular bone even after 4 weeks biodegradation, paramagnetic, cytocompatible and most importantly osteogenic. Our results encourage further research on Fe-based bone implants in in vivo.@en

Mechanical metamaterials exhibit unusual mechanical properties that originate from their topological design. Pentamode metamaterials are particularly interesting because they could be designed to possess any thermodynamically admissible elasticity tensor. In this study, we additively manufacture the metallic pentamode metamaterials from a biocompatible and mechanically strong titanium alloy (Ti-6Al-4V) using an energy distribution method developed for the powder bed fusion techniques. The mechanical properties of the developed materials were a few orders of magnitude higher than those of the similar topologies fabricated previously from polymers. Moreover, the elastic modulus and yield stress of the presented pentamode metamaterials were decoupled from their relative density, meaning that the metallic meta-biomaterials with independently tailored elastic and mass transport (permeability) properties could be designed for tissue regeneration purposes.@en

Extrusion-based 3D printing followed by debinding and sintering is a powerful approach that allows for the fabrication of porous scaffolds from materials (or material combinations) that are otherwise very challenging to process using other additive manufacturing techniques. Iron is one of the materials that have been recently shown to be amenable to processing using this approach. Indeed, a fully interconnected porous design has the potential of resolving the fundamental issue regarding bulk iron, namely a very low rate of biodegradation. However, no extensive evaluation of the biodegradation behavior and properties of porous iron scaffolds made by extrusion-based 3D printing has been reported. Therefore, the in vitro biodegradation behavior, electrochemical response, evolution of mechanical properties along with biodegradation, and responses of an osteoblastic cell line to the 3D printed iron scaffolds were studied. An ink formulation, as well as matching 3D printing, debinding and sintering conditions, was developed to create iron scaffolds with a porosity of 67%, a pore interconnectivity of 96%, and a strut density of 89% after sintering. X-ray diffracometry confirmed the presence of the α-iron phase in the scaffolds without any residuals from the rest of the ink. Owing to the presence of geometrically designed macropores and random micropores in the struts, the in vitro corrosion rate of the scaffolds was much improved as compared to the bulk counterpart, with 7% mass loss after 28 days. The mechanical properties of the scaffolds remained in the range of those of trabecular bone despite 28 days of in vitro biodegradation. The direct culture of MC3T3-E1 preosteoblasts on the scaffolds led to a substantial reduction in living cell count, caused by a high concentration of iron ions, as revealed by the indirect assays. On the other hand, the ability of the cells to spread and form filopodia indicated the cytocompatibility of the corrosion products. Taken together, this study shows the great potential of extrusion-based 3D printed porous iron to be further developed as a biodegradable bone substituting biomaterial.@en

Additively manufactured biodegradable porous iron has been only very recently demonstrated. Two major limitations of such a biomaterial are very low biodegradability and incompatibility with magnetic resonance imaging (MRI). Here, we present a novel biomaterial that resolves both of those limitations. We used extrusion-based 3D printing to fabricate ex situ-alloyed biodegradable iron-manganese scaffolds that are non-ferromagnetic and exhibit enhanced rates of biodegradation. We developed ink formulations containing iron and 25, 30, or 35 wt% manganese powders, and debinding and sintering process to achieve Fe-Mn scaffolds with 69% porosity. The Fe25Mn scaffolds had the ε-martensite and γ-austenite phases, while the Fe30Mn and Fe35Mn scaffolds had only the γ-austenite phase. All iron-manganese alloys exhibited weakly paramagnetic behavior, confirming their potential to be used as MRI-friendly bone substitutes. The in vitro biodegradation rates of the scaffolds were very much enhanced (i.e., 4.0 to 4.6 times higher than that of porous iron), with the Fe35Mn alloy exhibiting the highest rate of biodegradation (i.e., 0.23 mm/y). While the elastic moduli and yield strengths of the scaffolds decreased over 28 days of in vitro biodegradation, those values remained in the range of cancellous bone. The culture of preosteoblasts on the porous iron-manganese scaffolds revealed that cells could develop filopodia on the scaffolds, but their viability was reduced by the effect of biodegradation. Altogether, this research marks a major breakthrough and demonstrates the great prospects of multi-material extrusion-based 3D printing to further address the remaining issues of porous iron-based materials and, eventually, develop ideal bone substitutes. Statement of significance: 3D printed porous iron biomaterials for bone substitution still encounter limitations, such as the slow biodegradation and magnetic resonance imaging incompatibility. Aiming to solve the two fundamental issues of iron, we present ex-situ alloyed porous iron-manganese scaffolds fabricated by means of multi-material extrusion-based 3D printing. Our porous iron-manganese possessed enhanced biodegradability, non-ferromagnetic property, and bone-mimicking mechanical property throughout the in vitro biodegradation period. The results demonstrated a great prospect of multi-material extrusion-based 3D printing to further address the remaining challenges of porous iron-based biomaterials to be an ideal biodegradable bone substitutes.@en

The reconstruction of large mandibular defects with optimal aesthetic and functional outcomes remains a major challenge for maxillofacial surgeons. The aim of this study was to design patient-specific mandibular reconstruction implants through a semi-automated digital workflow and to assess the effects of topology optimization on the biomechanical performance of the designed implants. By using the proposed workflow, a fully porous implant (LA-implant) and a topology-optimized implant (TO-implant) both made of Ti-6Al-4V ELI were designed and additively manufactured using selective laser melting. The mechanical performance of the implants was predicted by performing finite element analysis (FEA) and was experimentally assessed by conducting quasi-static and cyclic biomechanical tests. Digital image correlation (DIC) was used to validate the FE model by comparing the principal strains predicted by the FEM model with the measured distribution of the same type of strain. The numerical predictions were in good agreement with the DIC measurements and the predicted locations of specimen failure matched the actual ones. No statistically significant differences (p < 0.05) in the mean stiffness, mean ultimate load, or mean ultimate displacement were detected between the LA- and TO-implant groups. No implant failures were observed during quasi-static or cyclic testing under masticatory loads that were substantially higher (>1000 N) than the average maximum biting force of healthy individuals. Given its relatively lower weight (16.5%), higher porosity (17.4%), and much shorter design time (633.3%), the LA-implant is preferred for clinical application. This study clearly demonstrates the capability of the proposed workflow to develop patient-specific implants with high precision and superior mechanical performance, which will greatly facilitate cost- and time-effective pre-surgical planning and is expected to improve the surgical outcome.@en

Porous biodegradable Mg and its alloys are considered to have a great potential to serve as ideal bone substitutes. The recent progress in additive manufacturing (AM) has prompted its application to fabricate Mg scaffolds with geometrically ordered porous structures. Extrusion-based AM, followed by debinding and sintering, has been recently demonstrated as a powerful approach to fabricating such Mg scaffolds, which can avoid some crucial problems encountered when applying powder bed fusion AM techniques. However, such pure Mg scaffolds exhibit a too high rate of in vitro biodegradation. In the present research, alloying through a pre-alloyed Mg-Zn powder was ultilized to enhance the corrosion resistance and mechanical properties of AM geometrically ordered Mg-Zn scaffolds simultaneously. The in vitro biodegradation behavior, mechanical properties, and electrochemical response of the fabricated Mg-Zn scaffolds were evaluated. Moreover, the response of preosteoblasts to these scaffolds was systematically evaluated and compared with their response to pure Mg scaffolds. The Mg-Zn scaffolds with a porosity of 50.3% and strut density of 93.1% were composed of the Mg matrix and MgZn2 second phase particles. The in vitro biodegradation rate of the Mg-Zn scaffolds decreased by 81% at day 1, as compared to pure Mg scaffolds. Over 28 days of static immersion in modified simulated body fluid, the corrosion rate of the Mg-Zn scaffolds decreased from 2.3 ± 0.9 mm/y to 0.7 ± 0.1 mm/y. The yield strength and Young's modulus of the Mg-Zn scaffolds were about 3 times as high as those of pure Mg scaffolds and remained within the range of those of trabecular bone throughout the biodegradation tests. Indirect culture of MC3T3-E1 preosteoblasts in Mg-Zn extracts indicated favorable cytocompatibility. In direct cell culture, some cells could spread and form filopodia on the surface of the Mg-Zn scaffolds. Overall, this study demonstrates the great potential of the extrusion-based AM Mg-Zn scaffolds to be further developed as biodegradable bone-substituting biomaterials.@en

Porous biomaterials are often used to treat large bony defects or fractured vertebras. Most of such biomaterials are made of metals and their alloys and have a pre-defined, fixed shape. Due to their predefined fixed shape, however, they are not suitable for implantation through minimally invasive surgical procedures. To overcome this problem, we designed three different deployable non-assembly mechanisms, which were manufactured using selective laser melting. These deployable geometries, including a bicapped cube, a bicapped trigonal antiprism, and a bicapped square antiprism, possess a large aspect ratio in their retracted state. Upon the application of an external force, they expand radially into their deployed load-bearing configuration. Using non-assembly manufacturing, revolute joints, wavelike elements, rigid rods and restrictions could be integrated into the design. The designs were manufactured in such a way that the least amount of support structures was required during the fabrication process. Additionally, the deployable structures were functional immediately after printing. Mechanical tests were performed to determine the forces required to deploy the designed structures and to determine their failure load. A maximum change of 322 ± 7% in the circumdiameter was found for the bicapped trigonal antiprism while the bicapped square antiprism showed the largest reduction in the height (61 ± 1%). A maximum force of 10.3 ± 1.6 N was required during the deployment process of the bicapped square antiprism 3. The bicapped antiprisms could support up to 1212 ± 45.5 N before they failed, while the bicapped cubes failed under a force of 232 ± 5.5 N. The elongated geometry of our designs makes them ideal for implantation using minimally invasive surgical procedures. Given the fact that these are the first non-assembly deployable bone substitutes manufactured using selective laser melting, further studies are required to make them suitable as orthopedic implants.@en

Background: Nuclear factor erythroid 2–related factor 2 (Nrf2) is a crucial transcription factor for cellular redox homeostasis. The association of Nrf2 with elderly female osteoporotic has yet to be fully described. The aim was to elucidate a potential age-dependent Nrf2 contribution to female osteoporosis in mice. Methods: Eighteen female wild type (WT) and 16 Nrf2-knockout (KO) mice were sacrificed at different ages (12 weeks = young mature adult and 90 weeks = old) to analyze their femurs. The morphological properties (trabecular and cortical) were evaluated by micro-computed tomography (μCT) and compared to gold standard histochemistry analysis. The quasi-static compression tests were performed to calculate the mechanical properties of bones. Additionally, the population of bone resorbing cells and aromatase expression by osteocytes was immunohistochemically evaluated and empty osteocyte lacunae was counted in cortical bone. Results: Old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness, cortical area, and bone fraction compared to old WT mice, regardless of no significant difference in skeletally mature young adult mice between WT and KO. Specifically, while all old WT mice showed thin metaphyseal trabeculae, trabecular bone was completely absent in 60% of old KO mice. Additionally, old KO mice showed significantly more osteoclast-like cells and fewer aromatase-positive osteocytes than WT mice, whereas the occurrence of empty osteocyte lacunae did not differ between both groups. Nrf2-KO mice further showed an age-dependently reduced fracture resilience compared to age-matched WT mice. Conclusion: Our results suggest that chronic Nrf2 loss can lead to age-dependent progression of female osteoporosis.@en