While conventionally manufactured metallic biomaterials can hardly meet all the requirements for bone implants including complex geometry, exact dimensions, adequate biodegradability, bone-matching mechanical properties, and biological function, two additional tools have recently appeared in the arsenal of biomaterials scientists which promise to deliver the desired combination of properties. First, the unique mechanical, electrical, and biological properties of graphene (Gr) and its derivatives (GDs), e.g., a Young's modulus up to 1 TPa, can be utilized to create metal matrix composites in which GDs of varied contents (typically not more than 2 wt%), sizes (lateral sizes from a few nanometers to several micrometers), surface areas (up to the theoretical value of 2630 m²/g), and layer numbers (typically up to 10) are embedded in the biodegradable metal matrix, thereby endowing the composite implants with extraordinary properties. Second, the distinct advantages of additive manufacturing (AM) make it possible for GD-containing composite materials to precisely mimic the complex shapes and structures of bones at multiple length scales. Here, a comprehensive review of the recent advances in the development of GD-containing biodegradable metal matrix composites (GBMMCs), ranging from composite fabrication, including composite powder preparation, and AM processes, to the evaluation of AM composites in terms of their mechanical and biological properties, is presented. Furthermore, the constraints in processing composite powders, the advantages and disadvantages of applicable AM techniques, and the mechanisms of mechanical reinforcement, biodegradation modulation, osteogenesis improvement, and cytotoxicity/antibacterial balance are critically analyzed. Thereafter, the foreseeable challenges faced in the development of the next-generation of bone implants based on GBMMCs are presented and some future directions of research are identified.

Medical devices contribute to the carbon footprint generated by the healthcare sector. The development of implants and biomaterials using recycled waste materials promotes sustainable advances in tissue engineering. Additively manufactured (AM) bone-substituting biomaterials with multifunctional properties, e.g., biodegradability, antibacterial and osteogenic potential, can contribute to sustainable healthcare. Biodegradable biomaterials eliminate secondary surgeries to remove implants, reduce post-surgical complications, and enhance patient recovery, thus decreasing the energy usage and waste associated with medical treatments. Herein, we present porous iron (Fe) scaffolds incorporating 20 vol% waste-derived eggshell particles for bone substitution. The Fe-eggshell scaffolds were fabricated using direct ink writing (DIW) technique and underwent post-AM heat treatment. During sintering, the eggshell's main component – CaCO₃, transformed into CaO. Atomic diffusion between α-Fe and CaO phases resulted in the formation of Ca₂Fe₂O₅ phase at the interface. The scaffolds were 70 % porous and displayed a biodegradation rate of 0.11 mm/year. The mechanical properties were comparable to trabecular bone and the scaffolds endured 3 million loading cycles at 0.7σ_y in r-SBF. The scaffolds showed apatite-forming ability, evidenced by the formation of (carbonaceous) hydroxyapatite, which are conducive to preosteoblast adhesion, proliferation, and differentiation. RT-qPCR analysis confirmed the osteogenic potential of the specimens as evidenced by the upregulated expression of osteopontin and osteocalcin as compared to Ti6Al4V controls. Furthermore, the scaffolds exhibited bactericidal activity (>3.9-log CFU reduction) against methicillin-sensitive and multidrug-resistant strains of Staphylococcus aureus and delayed their biofilm formation. Our research showcases the exceptional multifunctionality of DIW Fe-eggshell composite scaffolds for the sustainable development of orthopedic biomaterials. Statement of significance: We aim to improve the biofunctionalities and sustainability of biodegradable bone substitutes, by developing the extrusion-based 3D printed porous Fe composite scaffolds containing eggshell-derived CaO bioceramics. Our results demonstrated that Fe-eggshell scaffolds exhibited hydroxyapatite-forming ability in simulated body fluid, having mechanical properties in the range of trabecular bone even after 4 weeks biodegradation, supported the proliferation of preosteoblasts and upregulated the expression of osteogenic genes. Moreover, the scaffolds were bactericidal against methicillin-sensitive and multi-drug resistant strains Staphylococcus aureus and delayed their biofilm formation.

Additively manufactured (AM) biodegradable zinc alloys hold huge potential as promising candidates for bone defect and fracture repair, thanks to their suitable biodegradation rates and acceptable biocompatibility. However, the mechanical properties of AM zinc alloys developed so far, ductility in particular, fall short of the requirements for bone substitution. Here, we present Zn-1Mn and Zn-1Mn-0.4Mg alloy implants with unique microstructures, fabricated using laser powder bed fusion (LPBF). Notably, the LPBF Zn-Mn-Mg alloy exhibited an extraordinary balance of strength and ductility, with an ultimate tensile strength of 289 MPa, yield strength of 213.5 MPa, and elongation over 20 %, outperforming all previously reported AM zinc alloys. The simultaneously enhanced strength and ductility of the ternary alloy were attributed to the strong grain-refining effect of the Mg₂Zn₁₁ second phase and the synthetic strengthening caused by the dispersion of the MnZn₁₃ and Mg₂Zn₁₁ second phases inside the grains and at the grain boundaries. In addition, both alloys had similar rates of in vitro biodegradation (∼0.15 mm/year), properly aligned with the bone remodeling process, while also demonstrating favorable biocompatibility and upregulating multiple osteogenic markers. The Zn-Mn-Mg alloy showed even better osteogenic potential than the Zn-Mn alloy, owing to the addition of Mg. The combined attributes of the LPBF Zn-Mn-Mg ternary alloy indicated huge potential for its use as a bone repair material, especially for load-bearing bone fixation. Statement of significance: The mechanical properties of previously developed additively manufactured biodegradable zinc alloys, especially ductility, have not met the requirements for bone repair. Using laser powder bed fusion (LPBF), we fabricated Zn-1Mn and Zn-1Mn-0.4Mg alloy implants with unique microstructures. The LPBF Zn-Mn-Mg alloy demonstrated an exceptional balance of strength and ductility, achieving a tensile strength of 289 MPa, yield strength of 213.5 MPa, and elongation over 20 %, surpassing all reported AM zinc alloys. This study is the first to produce a directly printed biodegradable alloy meeting the mechanical requirements for bone fixation devices without post-processing. Additionally, the alloy exhibited moderate a biodegradation rate and excellent biocompatibility, underscoring its potential for load-bearing bone repair applications.

Additively manufactured (AM) iron (Fe)-based scaffolds have been developed as promising biodegradable bone-substituting biomaterials. Multi-material extrusion-based 3D printing has recently yielded Fe-manganese (Mn) alloy-based scaffolds that can resolve ferromagnetism and cytotoxicity associated with Fe-based biomaterials. Herein, we, for the first time, present the findings from in vivo study on extrusion-based AM FeMn-akermanite (Ak) scaffolds for critical-size bone defect repair. The scaffolds comprised Fe, 35 wt% Mn, and 20 or 30 vol% Ak, with microporous struts and 61–63 % porosity. Both scaffolds exhibited mechanical properties within the range of trabecular bone and provided suitable sites for Ca/P deposition during in vitro biodegradation. In vitro cell cultures demonstrated favorable cell responses without negating the osteogenic potential of cells. An in vivo study was conducted in a murine semi-orthotopic subcutaneous model. With this model, 4 bovine bone plugs were implanted subcutaneously with critical-size defects created at their cores. Scaffolds were placed into these critical-size defects to assess biodegradation and bone formation. After 16 weeks, the volume of scaffolds decreased by 6–8 %. The FeMn-20Ak scaffolds retained their yield strength and elastic modulus during the 16 weeks in vivo, whereas the mechanical integrity of FeMn-30Ak scaffolds deteriorated after mechanical push-out tests. Excellent osseointegration of both scaffold groups was apparent. 3D reconstruction of CT images revealed that FeMn-30Ak scaffolds had more newly formed tissue in the macro-pores than FeMn-20Ak. Altogether, our findings demonstrate the potential of AM FeMn-Ak scaffolds as biodegradable bone substitutes, encouraging further in vivo research in a large animal model.

Temporomandibular joint (TMJ) replacement prostheses often face limitations in accommodating translational movements, leading to unnatural kinematics and loading conditions, which affect functionality and longevity. Here, we investigate the potential of functionally graded materials (FGMs) in TMJ prostheses to enhance mandibular kinematics and reduce joint reaction forces. We develop a functionally graded artificial cartilage for the TMJ implant and evaluate five FGM designs: hard, hard-soft, and three FGM gradients with gradual transitions from 90% hard material to 0%, 10%, and 20%. These designs are 3D printed, mechanically tested under quasi-static compression, and simulated under physiological conditions. Results from computational modeling and experiments are compared to an intact mandible during incisal clenching and left group biting. The FGM design with a transition from 90% to 0% hard material improves kinematics by 19% and decreases perfomance by 3%, reduces joint reaction forces by 8% and 10%, and increases mandibular movement by 20% and 88% during incisal clenching and left group biting, respectively. These findings provide valuable insights for next-generation TMJ implants.

Additively manufactured (AM) biodegradable porous iron-manganese (FeMn) alloys have recently been developed as promising bone-substituting biomaterials. However, their corrosion fatigue behavior has not yet been studied. Here, we present the first study on the corrosion fatigue behavior of an extrusion-based AM porous Fe35Mn alloy under cyclic loading in air and in the revised simulated body fluid (r-SBF), including the fatigue crack morphology and distribution in the porous structure. We hypothesized that the fatigue behavior of the architected AM Fe35Mn alloy would be strongly affected by the simultaneous biodegradation process. We defined the endurance limit as the maximum stress at which the scaffolds could undergo 3 million loading cycles without failure. The endurance limit of the scaffolds was determined to be 90 % of their yield strength in air, but only 60 % in r-SBF. No notable crack formation in the specimens tested in air was observed even after loading up to 90 % of their yield strength. As for the specimens tested in r-SBF, however, cracks formed in the specimens subjected to loads exceeding 60 % of their yield strength appeared to initiate on the periphery and propagate toward the internal struts. Altogether, the results show that the extrusion-based AM porous Fe35Mn alloy is capable of tolerating up to 60 % of its yield strength for up to 3 million cycles, which corresponds to 1.5 years of use of load-bearing implants subjected to repetitive gait cycles. The fatigue performance of the alloy thus further enhances its potential for trabecular bone substitution subjected to cyclic compressive loading. Statement of significance: Fatigue behavior of extrusion-based AM porous Fe35Mn alloy scaffolds in air and revised simulated body fluid was studied. The Fe35Mn alloy scaffolds endured 90 % of their yield strength for up to 3 × 10⁶ loading cycles in air. Moreover, the scaffolds tolerated 3 × 10⁶ loading cycles at 60 % of their yield strength in revised simulated body fluid. The Fe35Mn alloy scaffolds exhibited a capacity of withstanding 1.5-year physiological loading when used as bone implants.

Additively manufactured (AM) biodegradable zinc (Zn) alloys have recently emerged as promising porous bone-substituting materials, due to their moderate degradation rates, good biocompatibility, geometrically ordered microarchitectures, and bone-mimicking mechanical properties. While AM Zn alloy porous scaffolds mimicking the mechanical properties of trabecular bone have been previously reported, mimicking the mechanical properties of cortical bone remains a formidable challenge. To overcome this challenge, we developed the AM Zn-3Mg alloy. We used laser powder bed fusion to process Zn-3Mg and compared it with pure Zn. The AM Zn-3Mg alloy exhibited significantly refined grains and a unique microstructure with interlaced α-Zn/Mg₂Zn₁₁ phases. The compressive properties of the solid Zn-3Mg specimens greatly exceeded their tensile properties, with a compressive yield strength of up to 601 MPa and an ultimate strain of >60 %. We then designed and fabricated functionally graded porous structures with a solid core and achieved cortical bone-mimicking mechanical properties, including a compressive yield strength of >120 MPa and an elastic modulus of ≈20 GPa. The biodegradation rates of the Zn-3Mg specimens were lower than those of pure Zn and could be adjusted by tuning the AM process parameters. The Zn-3Mg specimens also exhibited improved biocompatibility as compared to pure Zn, including higher metabolic activity and enhanced osteogenic behavior of MC3T3 cells cultured with the extracts from the Zn-3Mg alloy specimens. Altogether, these results marked major progress in developing AM porous biodegradable metallic bone substitutes, which paved the way toward clinical adoption of Zn-based scaffolds for the treatment of load-bearing bony defects. Statement of significance: Our study presents a significant advancement in the realm of biodegradable metallic bone substitutes through the development of an additively manufactured Zn-3Mg alloy. This novel alloy showcases refined grains and a distinctive microstructure, enabling the fabrication of functionally graded porous structures with mechanical properties resembling cortical bone. The achieved compressive yield strength and elastic modulus signify a critical leap toward mimicking the mechanical behavior of load-bearing bone. Moreover, our findings reveal tunable biodegradation rates and enhanced biocompatibility compared to pure Zn, emphasizing the potential clinical utility of Zn-based scaffolds for treating load-bearing bony defects. This breakthrough opens doors for the wider adoption of zinc-based materials in regenerative orthopedics.

Three commercial stents (Palmaz-Schatz, NIR, and BioMatrix) with either an open-cell (20% open-cell) or a closed-cell (80% closed-cell) design, and one new hybrid stent design were numerically modeled using the ABAQUS/Explicit finite element software (Dassault Systèmes, France) to compare their behaviors during deployment in a stenotic artery. The ABAQUS/Explicit dynamic explicit solver was utilized to efficiently capture the complex interactions between the balloon, stent, artery, and plaque during the stent expansion process. The effect of changing the material from stainless steel (SS 316L) to cobalt-chromium (CoCr) and platinum-chromium (PtCr), as well as the reduced thickness of struts from 0.1 mm to 0.08 mm, were investigated. The new hybrid stent design featured reduced axial strut spacing (from 1.2 mm to 0.8 mm), larger corner radii (from 0.2 mm to 0.3 mm), and smaller amplitudes in the ring (from 1.0 mm to 0.8 mm). For the simulations, a balloon-stent-artery model with plaque and average blood pressure of 80 mmHg was used. The results showed that the new hybrid stent did not perform worse in any of the studied biomechanical parameters compared to the commercial open-cell (20% expansion) and closed-cell (15% expansion) stents, and exhibited better performance in maximum expansion (22%) and recoil responses (5% recoil). Changing the material in the new hybrid stent from SS 316L to CoCr or PtCr improved the biomechanical behavior, such as expansion (25%), recoil (3%), and dogboning (0.9), but increased the maximum von Mises stress on the artery-plaque system by 18%. Reducing the strut thickness from 0.1 mm to 0.08 mm decreased the maximum stress on the artery-plaque system by 12%, but undesirably increased dogboning (1.1) and recoil (7%).

With the advancement of additive manufacturing (AM), customized vascular stents can now be fabricated to fit the curvatures and sizes of a narrowed or blocked blood vessel, thereby reducing the possibility of thrombosis and restenosis. More importantly, AM enables the design and fabrication of complex and functional stent unit cells that would otherwise be impossible to realize with conventional manufacturing techniques. Additionally, AM makes fast design iterations possible while also shortening the development time of vascular stents. This has led to the emergence of a new treatment paradigm in which custom and on-demand-fabricated stents will be used for just-in-time treatments. This review is focused on the recent advances in AM vascular stents aimed at meeting the mechanical and biological requirements. First, the biomaterials suitable for AM vascular stents are listed and briefly described. Second, we review the AM technologies that have been so far used to fabricate vascular stents as well as the performances they have achieved. Subsequently, the design criteria for the clinical application of AM vascular stents are discussed considering the currently encountered limitations in materials and AM techniques. Finally, the remaining challenges are highlighted and some future research directions are proposed to realize clinically-viable AM vascular stents. Statement of significance: Vascular stents have been widely used for the treatment of vascular disease. The recent progress in additive manufacturing (AM) has provided unprecedented opportunities for revolutionizing traditional vascular stents. In this manuscript, we review the applications of AM to the design and fabrication of vascular stents. This is an interdisciplinary subject area that has not been previously covered in the published review articles. Our objective is to not only present the state-of-the-art of AM biomaterials and technologies but to also critically assess the limitations and challenges that need to be overcome to speed up the clinical adoption of AM vascular stents with both anatomical superiority and mechanical and biological functionalities that exceed those of the currently available mass-produced devices.

Additive manufacturing (AM) technologies, particularly those based on powder bed fusion (PBF), most notably, selective laser melting (SLM) for metals, have in recent years emerged as unique fabrication methods for patient-specific implants made of metals and their alloys. The ability to manufacture complex geometries together with the other features of PBF has resulted in successful fabrication of previously unseen functional implants with reliable, reproducible, and predictable properties. The capability of SLM to manufacture a wide range of metals has made this process the most favored one in the manufacturing of implants, mostly for orthopedic applications. As such, it has received tremendous attention from both academia and industry to speed up the achievement of technological maturity, which is demonstrated by the ability to ensure the desired quality of SLM implants and reproducibility in a cost-effective manner. We will, in this chapter, address some of the critical aspects of PBF, particularly those of SLM, including the effects of geometrical design, process parameters, and material type on the quality and properties of AM implants. Finally, we will conclude this chapter with a discussion on the limitations, challenges, and outlook of SLM for implants.

The need for sustainable development has never been more urgent, as the world continues to struggle with environmental challenges, such as climate change, pollution, and dwindling natural resources. The use of renewable and recycled waste materials as a source of raw materials for biomaterials and tissue engineering is a promising avenue for sustainable development. Although tissue engineering has rapidly developed, the challenges associated with fulfilling the increasing demand for bone substitutes and implants remain unresolved, particularly as the global population ages. This review provides an overview of waste materials, such as eggshells, seashells, fish residues, and agricultural biomass, that can be transformed into biomaterials for bone tissue engineering. While the development of recycled metals is in its early stages, the use of probiotics and renewable polymers to improve the biofunctionalities of bone implants is highlighted. Despite the advances of additive manufacturing (AM), studies on AM waste-derived bone-substitutes are limited. It is foreseeable that AM technologies can provide a more sustainable alternative to manufacturing biomaterials and implants. The preliminary results of eggshell and seashell-derived calcium phosphate and rice husk ash-derived silica can likely pave the way for more advanced applications of AM waste-derived biomaterials for sustainably addressing several unmet clinical applications.

Practical applications of mechanical metamaterials often involve solving inverse problems aimed at finding microarchitectures that give rise to certain properties. The limited resolution of additive manufacturing techniques often requires solving such inverse problems for specific specimen sizes. Moreover, the candidate microarchitectures should be resistant to fatigue and fracture. Such a multi-objective inverse design problem is formidably difficult to solve but its solution is the key to real-world applications of mechanical metamaterials. Here, a modular approach titled “Deep-DRAM” that combines four decoupled models is proposed, including two deep learning (DL) models, a deep generative model based on conditional variational autoencoders, and direct finite element (FE) simulations. Deep-DRAM integrates these models into a framework capable of finding many solutions to the posed multi-objective inverse design problem based on random-network unit cells. Using an extensive set of simulations as well as experiments performed on 3D printed specimens, it is demonstrate that: 1) the predictions of the DL models are in agreement with FE simulations and experimental observations, 2) an enlarged envelope of achievable elastic properties (e.g., rare combinations of double auxeticity and high stiffness) is realized using the proposed approach, and 3) Deep-DRAM can provide many solutions to the considered multi-objective inverse design problem.

Additively manufactured (AM) degradable porous metallic biomaterials offer unique opportunities for satisfying the design requirements of an ideal bone substitute. Among the currently available biodegradable metals, iron has the highest elastic modulus, meaning that it would benefit the most from porous design. Given the successful preclinical applications of such biomaterials for the treatment of cardiovascular diseases, the moderate compatibility of AM porous iron with osteoblast-like cells, reported in earlier studies, has been surprising. This may be because, as opposed to static in vitro conditions, the biodegradation products of iron in vivo are transported away and excreted. To better mimic the in situ situations of biodegradable biomaterials after implantation, we compared the biodegradation behavior and cytocompatibility of AM porous iron under static conditions to the conditions with dynamic in situ-like fluid flow perfusion in a bioreactor. Furthermore, the compatibility of these scaffolds with four different cell types was evaluated to better understand the implications of these implants for the complex process of natural wound healing. These included endothelial cells, L929 fibroblasts, RAW264.7 macrophage-like cells, and osteoblastic MG-63 cells. The biodegradation rate of the scaffolds was significantly increased in the perfusion bioreactor as compared to static immersion. Under either condition, the compatibility with L929 cells was the best. Moreover, the compatibility with all the cell types was much enhanced under physiomimetic dynamic flow conditions as compared to static biodegradation. Our study highlights the importance of physiomimetic culture conditions and cell type selection when evaluating the cytocompatibility of degradable biomaterials in vitro. Statement of Significance: Additively manufactured (AM) degradable porous metals offer unique opportunities for the treatment of large bony defects. Despite the successful preclinical applications of biodegradable iron in the cardiovascular field, the moderate compatibility of AM porous iron with osteoblast-like cells was reported. To better mimic the in vivo condition, we compared the biodegradation behavior and cytocompatibility of AM porous iron under static condition to dynamic perfusion. Furthermore, the compatibility of these scaffolds with various cell types was evaluated to better simulate the process of natural wound healing. Our study suggests that AM porous iron holds great promise for orthopedic applications, while also highlighting the importance of physio-mimetic culture conditions and cell type selection when evaluating the cytocompatibility of degradable biomaterials in vitro.

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.

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.

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.

In the present research, a composite with a magnesium alloy (WE43) as the matrix and Akermanite as the bioactive and reinforcing agent was fabricated by friction stir processing (FSP), resulting in a microstructure with uniformly distributed fine grains, second-phase particles and micro-sized Akermanite particles. The effect of an addition of Akermanite to the alloy on the mechanical properties and corrosion resistance of the resulting composite was investigated. The compressive strength and ductility of the composite were found to be significantly higher than those of the monolithic WE43 alloy. The value of yield strength of the WE43 sample increased from 75 MPa up to 119 and 225 MPa for WE43-6P and WE43-A-6P samples, respectively. Also, the value of the ultimate compressive strength of the WE43 sample increased from 210 MPa up to 240 and 362 MPa for WE43-6P and WE43-A-6P samples, respectively. The value of elongation for WE43, WE43-6P, and WE43-A-6P samples were 4.5%, 16%, and 22%, respectively. The EIS test showed that the corrosion mechanism of WE43 sample is a combination of localized pitting and uniform corrosion, which shifted towards more uniform corrosion with higher corrosion resistance by applying FSP and adding Akermanite powder. The potentiodynamic polarization and in vitro immersion tests confirmed this finding, as evidenced by the increase in polarization resistance from 0.192 for the monolithic WE43 alloy up to 0.339 and 0.609 kΩ/cm² for WE43-6P and WE43-A-6P samples, respectively. The mass loss rate of the WE43 sample decreased from 20.82 to 10.13 mm per year for the WE43-A-6P sample after 312 h immersion in SBF solution. All tests approved that by applying FSP and adding Akermanite to WE43, the corrosion resistance in the SBF solution could be significantly enhanced.

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.

Additive manufacturing (AM, also known as 3D printing) is an advanced manufacturing technique that has enabled progress in the design and fabrication of customised or patient-specific (meta-)biomaterials and biomedical devices (e.g., implants, prosthetics, and orthotics) with complex internal microstructures and tuneable properties. In the past few decades, several design guidelines have been proposed for creating porous lattice structures, particularly for biomedical applications. Meanwhile, the capabilities of AM to fabricate a wide range of biomaterials, including metals and their alloys, polymers, and ceramics, have been exploited, offering unprecedented benefits to medical professionals and patients alike. In this review article, we provide an overview of the design principles that have been developed and used for the AM of biomaterials as well as those dealing with three major categories of biomaterials, i.e., metals (and their alloys), polymers, and ceramics. The design strategies can be categorised as: library-based design, topology optimisation, bio-inspired design, and meta-biomaterials. Recent developments related to the biomedical applications and fabrication methods of AM aimed at enhancing the quality of final 3D-printed biomaterials and improving their physical, mechanical, and biological characteristics are also highlighted. Finally, examples of 3D-printed biomaterials with tuned properties and functionalities are presented.

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.