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.

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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.

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Porous Ti-6Al-4V scaffolds fabricated by means of selective laser melting (SLM),
having controllable geometrical features and preferable mechanical properties, have been developed as a class of biomaterials that hold promising potential for bone repair. However, the inherent bio-inertness of the Ti-6Al-4V alloy as the matrix of the scaffolds results in a lack in the ability to stimulate bone ingrowth and regeneration. The aim of the present study was to develop a bioactive
coating on the struts of SLM Ti-6Al-4V scaffolds in order to add the desired surface osteogenesis ability. Mesoporous bioactive glasses (MBGs) coating was applied on the strut surfaces of the SLM Ti-6Al-4V scaffolds through spin coating, followed by a heat treatment. It was found that the coating could maintain the characteristic mesoporous structure and chemical composition of
MBG, and establish good interfacial adhesion to the Ti-6Al-4V substrate. The compressive strength and pore interconnectivity of the scaffolds were not affected by the coating. Moreover, the results obtained from in vitro cell culture experiments demonstrated that the attachment, proliferation, and differentiation of human bone marrow stromal cells (hBMSCs) on the MBG-coated Ti-6Al-4V
scaffolds were improved as compared with those on the conventional bioactive glass (BG)-coated Ti-6Al-4V scaffolds and bare-metal Ti-6Al-4V scaffolds. Our results demonstrated that the MBG coating by using the spinning coating method could be an effective approach to achieving enhanced surface biofunctionalization for SLM Ti-6Al-4V scaffolds.@en

The present research was aimed at developing magnesium-matrix composites that could allow effective control over their physiochemical and mechanical responses when in contact with physiological solutions. A biodegradable, bioactive ceramic - bredigite was chosen as the reinforcing phase in the composites, based on the hypothesis that the silicon- and magnesium-containing ceramic could protect magnesium from fast corrosion and at the same time stimulate cell proliferation. Methods to prepare composites with integrated microstructures - a prerequisite to achieve controlled biodegradation were developed. A systematic experimental approach was taken in order to elucidate the in vitro biodegradation mechanisms and kinetics of the composites. It was found that the composites with 20–40% homogenously dispersed bredigite particles, prepared from powders, could indeed significantly decrease the degradation rate of magnesium by up to 24 times. Slow degradation of the composites resulted in the retention of the mechanical integrity of the composites within the strength range of cortical bone after 12 days of immersion in a cell culture medium. Cell attachment, cytotoxicity and bioactivity tests confirmed the stimulatory effects of bredigite embedded in the composites on the attachment, viability and differentiation of bone marrow stromal cells. Thus, the multiple benefits of adding bredigite to magnesium in enhancing degradation behavior, mechanical properties, biocompatibility and bioactivity were obtained. The results from this research showed the excellent potential of the bredigite-containing composites for bone implant applications, thus warranting further in vitro and in vivo research.

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Iron-matrix composites with calcium silicate (CS) bioceramic as the reinforcing phase were fabricated through powder metallurgy processes. The microstructures, mechanical properties, apatite deposition and biodegradation behavior of the Fe-CS composites, as well as cell attachment and proliferation on
their surfaces, were characterized. In the range of CS weight percentages selected in this study, the composites possessed compact structures and showed differently decreased bending strengths as compared with pure iron. Immersion tests in simulated body fluid (SBF) revealed substantially enhanced deposition of CaP on the surfaces of the composites as well as enhanced degradation rates as compared with pure iron. In addition, the composite containing 20% CS showed a superior ability to stimulate hBMSCs proliferation when compared to pure iron. Our results suggest that incorporating calcium silicate particles into iron could be an effective approach to developing iron-based biodegradable bone implants with improved biomedical performance.@en

Biodegradable metal matrix composites (MMCs) with pure magnesium as the matrix and bioceramic calcium silicate (CS) as the reinforcement phase were fabricated by means of spark plasma sintering (SPS). The microstructure, mechanical properties and degradation behavior of the composites as well as the cellular responses to these composites were investigated. The formation of CS networks in the Mg matrix was observed when the CS content reached 20%. Among the composites with CS weight percentages ranging from 10% to 40%, the composite containing 20% CS possessed the highest structural compactness and compressive strength. Immersion tests in simulated body fluid (SBF) revealed that the Mg-20% CS composite exhibited a substantially enhanced corrosion resistance as compared with pure Mg, which was attributed to the formation of a hydroxyapatite (HA) layer on the surface as a result of the presence of the CS networks throughout the Mg matrix. In addition, ionic products from the interaction between the Mg-20% CS composite and SBF brought about a significant stimulatory effect on the alkaline phosphate (ALP) expression of MC3T3-E1 osteoblast cells. Our results indicate that CS is an effective reinforcement phase to improve both the corrosion resistance and bioactivity of Mg and the Mg-CS composites developed in this research are able to overcome the inherent drawbacks of magnesium as a biodegradable implant material.

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