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.

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.

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.

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.

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.

Additively manufactured (AM) biodegradable magnesium (Mg) scaffolds with precisely controlled and fully interconnected porous structures offer unprecedented potential as temporary bone substitutes and for bone regeneration in critical-sized bone defects. However, current attempts to apply AM techniques, mainly powder bed fusion AM, for the preparation of Mg scaffolds, have encountered some crucial difficulties related to safety in AM operations and severe oxidation during AM processes. To avoid these difficulties, extrusion-based 3D printing has been recently developed to prepare porous Mg scaffolds with highly interconnected structures. However, limited bioactivity and a too high rate of biodegradation remain the major challenges that need to be addressed. Here, we present a new generation of extrusion-based 3D printed porous Mg scaffolds that are coated with MgF2 and MgF2-CaP to improve their corrosion resistance and biocompatibility, thereby bringing the AM scaffolds closer to meeting the clinical requirements for bone substitutes. The mechanical properties, in vitro biodegradation behavior, electrochemical response, and biocompatibility of the 3D printed Mg scaffolds with a macroporosity of 55% and a strut density of 92% were evaluated. Furthermore, comparisons were made between the bare scaffolds and the scaffolds with coatings. The coating not only covered the struts but also infiltrated the struts through micropores, resulting in decreases in both macro- and micro-porosity. The bare Mg scaffolds exhibited poor corrosion resistance due to the highly interconnected porous structure, while the MgF2-CaP coatings remarkably improved the corrosion resistance, lowering the biodegradation rate of the scaffolds down to 0.2 mm y-1. The compressive mechanical properties of the bare and coated Mg scaffolds before and during in vitro immersion tests for up to 7 days were both in the range of the values reported for the trabecular bone. Moreover, direct culture of MC3T3-E1 preosteoblasts on the coated Mg scaffolds confirmed their good biocompatibility. Overall, this study clearly demonstrated the great potential of MgF2-CaP coated porous Mg prepared by extrusion-based 3D printing for further development as a bone substitute. This journal is

Biodegradable porous magnesium (Mg) scaffolds are promising for application in the regeneration of critical-sized bone defects. Although additive manufacturing (AM) carries the promise of offering unique opportunities to fabricate porous Mg scaffolds, current attempts to apply the AM approach to fabricating Mg scaffolds have encountered some crucial issues, such as those related to safety in operation and to the difficulties in composition control. In this paper, we present a room-temperature extrusion-based AM method for the fabrication of topologically ordered porous Mg scaffolds. It is composed of three steps, namely (i) preparing a Mg powder loaded ink with desired rheological properties, (ii) solvent-cast 3D printing (SC-3DP) of the ink to form scaffolds with 0 °/ 90 °/ 0 ° layers, and (iii) debinding and sintering to remove the binder in the ink and then get Mg powder particles bonded by applying a liquid-phase sintering strategy. A rheological analysis of the prepared inks with 54, 58 and 62 vol% Mg powder loading was performed to reveal their viscoelastic properties. Thermal-gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), carbon/sulfur analysis and scanning electron microscopy (SEM) indicated the possibilities of debinding and sintering at one single step for fabricating pure Mg scaffolds with high fidelity and densification. The resulting scaffolds with high porosity contained hierarchical and interconnected pores. This study, for the first time, demonstrated that the SC-3DP technique presents unprecedented possibilities to fabricate Mg-based porous scaffolds that have the potential to be used as a bone-substituting material. Statement of Significance: Biodegradable porous magnesium scaffolds are promising for application in the regeneration of critical-sized bone defects. Although additive manufacturing (AM) carries the promise of offering unique opportunities to fabricate porous magnesium scaffolds, current attempts to apply the AM approach to fabricating magnesium scaffolds still have some crucial limitations. This study demonstrated that the solvent-cast 3D printing technique presents unprecedented possibilities to fabricate Mg-based porous scaffolds. The judicious chosen of formulated binder system allowed for the negligible binder residue after debinding and the short-time liquid-phase sintering strategy led to a great success in sintering pure magnesium scaffolds. The resulting scaffolds with hierarchical and interconnected pores have great potential to be used as a bone-substituting material.

Additively manufactured (AM) biodegradable porous zinc exhibits great potential as a promising bone-substituting biomaterial. However, there is no information whatsoever available regarding its corrosion fatigue behavior. In this study, we used direct metal printing to fabricate topologically ordered biodegradable porous zinc based on a diamond unit cell. We compared the compression-compression fatigue behavior of AM porous zinc in air and in revised simulated body fluid (r-SBF). The fatigue strength of AM porous zinc was high in air (i.e., 70% of its yield strength) and even higher in r-SBF (i.e., 80% of its yield strength). The high value of the relative fatigue strength in air could be attributed to the good ductility of pure zinc itself. The formation of corrosion products around the strut junctions might explain the higher fatigue strength of AM zinc in r-SBF. Furthermore, we compared the fatigue behavior of a uniform design of the AM porous zinc with a functionally graded design. The functionally graded structure exhibited higher relative fatigue strengths than the uniform structure. The inspection of the fatigue crack distribution revealed that the functionally graded design controlled the sequence of crack initiation, which occurred early in the thicker struts and moved towards the thinner struts over time. The theoretical fatigue life models suggest that optimizing the functionally graded structure could be used as an effective means to improve the fatigue life of AM porous zinc. In conclusion, the favorable fatigue behavior of AM porous zinc further highlights its potential as a promising bone-substituting biomaterial. Statement of Significance: Additively manufactured (AM) biodegradable porous zinc exhibits great potential for the treatment of large bony defects. However, there is no information available regarding its corrosion fatigue behavior. Here, we compared the fatigue behavior of AM porous zinc in air and in revised simulated body fluid (r-SBF). The fatigue strength of AM porous Zn was even higher in r-SBF than in air, which were attributed to the formation of corrosion products. Furthermore, we found that the functionally graded structure controlled the sequence of crack initiation in differently sized struts and exhibited higher relative fatigue strengths than the uniform structure, suggesting that optimizing the functionally graded structure could be an effective means to improve the fatigue life of AM porous Zn.