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.

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The ideal bone substituting biomaterials should possess bone-mimicking mechanical properties; have of porous interconnected structure, and adequate biodegradation behaviour to enable full recovery of bony defects. Direct metal printed porous scaffolds hold potential to satisfy all these requirements and were additively manufactured (AM) from atomized WE43 magnesium alloy powder with grain sizes between 20 and 60 μm. Their micro-structure, mechanical properties, degradation behavior and biocompatibility was then evaluated in vitro. Firstly, post-processing values nicely followed design parameters. Next, Young's moduli were similar to that of trabecular bone (i.e., E = 700–800 MPa) even after 28 days of simulated in vivo-like corrosion by in vitro immersion. Also, a relatively moderate hydrogen evolution, corresponding to a calculated 19.2% of scaffold mass loss, was in good agreement with 20.7% volume reduction as derived from reconstructed μCT images. Finally, only moderate cytotoxicity (i.e., level 0, <25%), even after extensive ISO 10993-conform testing for 72 h using MG-63 cells, was determined using WE43 extracts (2 way ANOVA, post-hoc Tukey's multiple comparisons test; α = 0.05). Cytotoxicity was further evaluated by direct live-dead staining assays, revealing a higher cell death in static culture. However, intimate cell-metal contact was observed by SEM. In summary, while pure WE43 may not yet be an ideal surface for cell adhesion, this novel AM process allows for adjusting biodegradation through topological design. Our approach holds tremendous potential to develop functional and biodegradable implants for orthopaedic applications.@en

An ideal bone substituting material should be bone-mimicking in terms of mechanical properties, present a precisely controlled and fully interconnected porous structure, and degrade in the human body to allow for full regeneration of large bony defects. However, simultaneously satisfying all these three requirements has so far been highly challenging. Here we present topologically ordered porous magnesium (WE43) scaffolds based on the diamond unit cell that were fabricated by selective laser melting (SLM) and satisfy all the requirements. We studied the in vitro biodegradation behavior (up to 4 weeks), mechanical properties and biocompatibility of the developed scaffolds. The mechanical properties of the AM porous WE43 (E = 700-800 MPa) scaffolds were found to fall into the range of the values reported for trabecular bone even after 4 weeks of biodegradation. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), electrochemical tests and μCT revealed a unique biodegradation mechanism that started with uniform corrosion, followed by localized corrosion, particularly in the center of the scaffolds. Biocompatibility tests performed up to 72 h showed level 0 cytotoxicity (according to ISO 10993-5 and -12), except for one time point (i.e., 24 h). Intimate contact between cells (MG-63) and the scaffolds was also observed in SEM images. The study shows for the first time that AM of porous Mg may provide distinct possibilities to adjust biodegradation profile through topological design and open up unprecedented opportunities to develop multifunctional bone substituting materials that mimic bone properties and enable full regeneration of critical-size load-bearing bony defects. Statement of Significance: The ideal biomaterials for bone tissue regeneration should be bone-mimicking in terms of mechanical properties, present a fully interconnected porous structure, and exhibit a specific biodegradation behavior to enable full regeneration of bony defects. Recent advances in additive manufacturing have resulted in biomaterials that satisfy the first two requirements but simultaneously satisfying the third requirement has proven challenging so far. Here we present additively manufactured porous magnesium structures that have the potential to satisfy all above-mentioned requirements. Even after 4 weeks of biodegradation, the mechanical properties of the porous structures were found to be within those reported for native bone. Moreover, our comprehensive electrochemical, mechanical, topological, and biological study revealed a unique biodegradation behavior and the limited cytotoxicity of the developed biomaterials.

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