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L.J. Li

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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 high-fidelity three-dimensional (3D) tissue models can minimize the need for animal models in clinical medicine and drug development. However, physical limitations regarding the distances within which diffusion processes are effective impose limitations on the size of such constructs. That is because larger-size constructs experience necrosis, especially in their centers, due to the cells residing deep inside such constructs not receiving enough oxygen and nutrients. This hampers the sustained in vitro growth of the tissues which is required for achieving functional microtissues. To address this challenge, we used three types of 3D printing technologies to create perfusable networks at different length scales and integrate them into such constructs. Toward this aim, networks incorporating porous conduits with increasingly complex configurations were designed and fabricated using fused deposition modeling, stereolithography, and two-photon polymerization while optimizing the printing conditions for each of these technologies. Furthermore, following network embedding in hydrogels, contrast agent-enhanced micro-computed tomography and confocal fluorescence microscopy were employed to characterize one of the essential network functionalities, namely the diffusion function. The investigations revealed the effects of various design parameters on the diffusion behavior of the porous conduits over 24 h. We found that the number of pores exerts the most significant influence on the diffusion behavior of the contrast agent, followed by variations in the pore size and hydrogel concentration. The analytical approach and the findings of this study establish a solid base for a new technological platform to fabricate perfusable multiscale 3D porous networks with complex designs while enabling the customization of diffusion characteristics to meet specific requirements for sustained in vitro tissue growth. Statement of significance: This study addresses an essential limitation of current 3D tissue engineering, namely, sustaining tissue viability in larger constructs through optimized nutrient and oxygen delivery. By utilizing advanced 3D printing techniques this research proposes the fabrication of perfusable, multiscale and customizable networks that enhance diffusion and enable cell access to essential nutrients throughout the construct. The findings highlighted the role of network characteristics on the diffusion of a model compound within a hydrogel matrix. This work represents a promising technological platform for creating advanced in vitro 3D tissue models that can reduce the use of animal models in research involving tissue regeneration, disease models and drug development. ...