A bstract This study was the first attempt to design, fabricate, and evaluate multi-material bone scaffolds composed of Ti6Al4V and akermanite (Ca₂Mg(Si₂O₇), Ak), produced via direct ink writing (DIW), followed by sintering. Two scaffold architectures were developed (i.e., monolithic and core-shell) aimed at combining the mechanical strength of the Ti alloy with the osteoinductive properties of Ak. Uniaxial compression testing demonstrated that the core-shell scaffolds exhibited higher relative-density-normalized elastic moduli (up to 7.65 ± 0.35 GPa) and yield strengths (up to 444.7 ± 8.1 MPa) than the monolithic designs, namely Ti6Al4V-only scaffolds (elastic modulus: 4.29 ± 0.18 GPa; yield strength: 230.9 ± 1.7 MPa) and 90% Ti6Al4V/10% Ak composite scaffolds (elastic modulus: 3.05 ± 0.08 GPa; yield strength: 24.7 ± 1.4 MPa).The enhanced mechanical performance was attributed to interfacial reinforcement and optimized material distribution. Bioactivity assays in r-SBF revealed surface Ca–P deposition on akermanite-containing scaffolds by SEM and EDS, a response not observed on Ti6Al4V only specimens. Complementary ICP-OES showed marked depletion of phosphate and calcium ions, consistent with rapid HAp nucleation and growth, and substantial silicon release in composite samples, a known pro-osteogenic stimulus. Cell culture assays further confirmed the cytocompatibility of the Ti6Al4V, composite and core-shell scaffolds for preosteoblasts. Furthermore, SEM imaging showed that all the scaffolds supported cell attachment and evidenced a distinct cell spatial distribution depending on scaffold composition and architecture. These results contribute to advancing the scaffold design for bone repair and regeneration by proposing DIW-fabricated Ti6Al7V/Ak core-shell scaffolds that show potential as customizable, load-bearing implants with improved mechanical properties and surface bioactivity relative to the Ti6Al4V scaffolds.

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.

The optimization of post-processing heat treatment for selective laser melted Ti-6Al-4V remains challenging due to the strong nonlinear coupling between thermal history, microstructure, and hardness. Existing predictive models are typically limited by small datasets and narrow process coverage, particularly for post-heat-treatment hardness. In this study, a machine learning framework was developed to predict the Vickers hardness of heat-treated SLM Ti-6Al-4V using a curated multi-source dataset integrating experimental measurements (19 samples), literature-derived data (42), and 200 synthetically generated samples via Stratified Bootstrap combined with Gaussian Copula Noise. Fifteen regression models were systematically benchmarked using cross-validation. Among them, the Voting Regressor achieved the highest predictive accuracy (R² ≈ 0.92, MAE ≈ 7.8 HV), demonstrating robust generalization across diverse heat-treatment conditions. Explainable artificial intelligence analysis revealed that microstructural characteristics and heat-treatment parameters are the dominant drivers of hardness, in agreement with phase-transformation mechanisms governing α′ decomposition and α + β stabilization. The proposed framework provides a quantitative and interpretable tool for rational heat-treatment design of SLM Ti-6Al-4V, reducing reliance on empirical trial-and-error approaches and enabling data-driven process optimization.

Zinc (Zn) has emerged as a promising biodegradable metal for bone tissue engineering, yet fabricating porous scaffolds via laser-based additive manufacturing (AM) remains challenging due to Zn evaporation. This study presents the successful fabrication of porous Zn scaffolds via extrusion-based AM through systematic ink formulation and sintering optimization. Printability was optimized through rheological analysis of 50–56 vol % Zn-loaded inks, while sintering conditions were refined within a precise temperature window. SEM and micro-CT characterized sintering quality and quantified pore defects. Optimal scaffolds, printed with 53 vol % ink and sintered at 415 °C for 5 h, achieved 40 ± 3% absolute porosity with minimal evaporation, attributed to a hybrid solid-liquid phase sintering mechanism. The scaffolds exhibited trabecular bone-matching mechanical properties with compressive yield strength of 16.1 ± 1.3 MPa and elastic modulus of 1.4 ± 0.1 GPa. In vitro biodegradation in r-SBF showed a corrosion rate of 0.03 ± 0.01 mm/year after 28 days, with biodegradation products including ZnO, Ca₃(PO₄)₂, and Zn-phosphate/chloride hydrates. Electrochemical tests demonstrated increasing polarization resistance (21.1 ± 3.8 kΩ·cm²) and passivation behavior. Indirect cytocompatibility assays showed > 90% metabolic activity for MC3T3-E1 cells in ≤ 50% Zn extracts, while direct seeding confirmed cell adhesion. These results establish extrusion-based AM as a viable route for fabricating Zn scaffolds with tailored porosity, controlled biodegradation, bone-like properties, and acceptable cytocompatibility, advancing the development of Zn-based biodegradable implants. Statement of significance Although laser-based additive manufacturing of pure zinc and its alloys is becoming increasingly mature, its inherent drawbacks, such as evaporation-driven composition loss and melt-pool instabilities, remain non-negligible and underscore the need to develop and apply alternative AM strategies for Zn-based bone scaffolds. We presented an extrusion-based route to fabricate porous Zn bone scaffolds and establish an end-to-end workflow spanning ink formulation, debinding, sintering, and multi-scale characterization. By tailoring the binder system and defining a robust thermal window, we achieved high-fidelity architectures with densified struts. The resulting scaffolds displayed bone-mimicking mechanical behavior together with predictable in-vitro degradation and cytocompatibility. Our work positions extrusion-based 3D printing as a practical manufacturing platform for Zn-based biodegradable bone substitutes.

Additive manufacturing (AM), also known as 3D printing, is gaining the attention of various industries as a viable alternative to conventional manufacturing, empowering design freedom, novel architectures, composition control, and sustainability. Meanwhile, metal matrix composites (MMCs) are being investigated for orthopedic implant applications due to their flexibility to achieve excellent strength, corrosion resistance, and bioactivity. Combining these two research fronts by utilizing AM for manufacturing multi-functional MMC bone scaffolds, having specific structures and compositions, has led to the recent development of a new generation of biomaterials with enhanced material properties not achievable with monolithic counterparts. Aimed at understanding the status of the research on the topic and identifying the remaining challenges, this review article discusses the utilization of AM for realizing the design vision of different MMC scaffolds, focusing on the synergistic combination of mechanical and biological characteristics, such as enhanced biodegradability, strength, and osteogenic properties. It starts by discussing the requirements for orthopedic implants and different AM techniques utilized thus far for manufacturing them, especially MMC orthopedic implants. Then, it delves into different MMCs, including Ti-, Mg-, and Fe-matrix composites that have been 3D printed into bone-substituting scaffolds and discusses their recent progress and specific characteristics. Finally, we identify the knowledge gaps and potential directions for developing MMCs further toward clinically viable, advanced orthopedic implants.

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.

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) 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%).

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.

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.

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.

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.

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.

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.

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.

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.

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.