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.

The growing need for personalized medical solutions has highlighted the importance of advancements in designing and producing patient-specific medical devices. Conventional manufacturing processes are effective in producing generic devices but often struggle to accommodate the unique anatomical variations of individual patients. This limitation may increase the risk of unfavorable surgical results and complications. Introducing 3D printing, or additive manufacturing (AM), has created new opportunities for the rapid and precise fabrication of customized implants, prosthetics, and orthotics tailored to fit patient anatomies. This technology not only enhances the functionality and durability of these devices but also contributes to faster recovery and improved patient outcomes.

However, several challenges remain: how to streamline the design process to deliver these tailored solutions swiftly and efficiently without compromising functionality, longevity, or durability. This thesis addresses these challenges by exploring strategies for integrating advanced computational models, design optimization techniques, and workflow automation into medical device design and production. These approaches aim to reduce the time from the initial concept to the final product, ensuring patients receive customized solutions promptly.

In addition to exploring the benefits of customization, this thesis investigates the use of generic but adaptable implants that can be quickly tailored to individual patient needs. This approach balances the need for rapid production with maintaining high standards of implant performance and patient outcomes, staying in the one-design-fits-all approach...

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.

Biocompatible and shape-morphing metallic structures have been proposed for musculoskeletal applications to provide structural support to bony tissues. However, fabricating these structures to conform to a wide range of curvatures, including both single and double curvatures, remains a significant challenge. In this study, we present and analyze structures featuring a regular tiling network connected by spherical joints, forming a chain mail-like mechanism capable of adapting to complex geometries with clay-like flexibility. Simulations using a multibody kinematics model show that parameters such as unit cell shape, dimension ratios, and substrate curvature affect the shape-matching abilities of the structure. Experimental validation using specimens additively manufactured through laser-based powder bed fusion (from Ti6Al4V) and full-field strain measurements performed through digital image correlation confirms the simulation results, demonstrating that reducing structural density (i.e., fewer bodies, struts, and joints per unit area) improves shape adaptability. However, the improved shape morphing capability often comes at the expense of mechanical strength under uni-axial tensile loads. These findings provide a framework for optimizing structures designed to achieve efficient surface conformance and adaptability in load-bearing applications.

Incorporating shape-morphing capability into 3D microprinting enables the fabrication of 4D-printed microarchitectures as proof-of-concept actuators for potential use in soft robotics and microfluidic systems. The ability of these 3D microstructures to actuate rapidly and reversibly enables precise, non-invasive, and controllable deformation. In this study, we investigated the programmable shape-morphing behavior of 3D microarchitectures fabricated using two-photon polymerization (2PP) of a well-established temperature-responsive hydrogel, poly(N-isopropylacrylamide) (pNIPAM). We first systematically studied how 2PP 3D printing parameters (e.g., laser power, scanning speed) and the chemical composition of pNIPAM, including monomer and crosslinker, influence the shape morphing of bilayer microstructures within a temperature range of ~ 32 °C to 60 °C. The (thermo)mechanical properties of the hydrogels, including the Young’s modulus, thermal expansion coefficients, and angular deflection, were also measured at different laser doses and temperatures. Based on these experimental measurements, we calibrated a thermomechanical model capable of predicting the shape morphing of 4D-printed microarchitectures. These microarchitectures served as proof-of-concept actuators, demonstrating the potential of programmable microscale soft robotics and microfluidic systems. The findings provide design guidelines for engineering stimuli-responsive 3D microstructures, highlighting limitations and opportunities for future integration into functional soft robotic or microfluidic systems made of a single material.

Emerging 4D printing techniques have enabled the realization of smart materials whose shape or properties can change with time. Two important phenomena play important roles in the 4D printing of shape memory polymeric materials. First, the anisotropic deformation of the printed filaments due to residual stresses can be harnessed to create out-of-plane shape transformations. Second, the unavoidable formation of micro-defects during the printing processes often affects the programmability of the printed object. Here, we propose a design approach that harnesses these two effects occurring during fused deposition modeling to create tailor-made curved geometries from initially 2D flat disks. We first determined the size and distribution of the imperfections formed within printed structures by varying two printing parameters namely the printing speed and the number of printed materials. Spatially varying the printing speed and combining polylactic acid filaments with a softer material without shape memory properties allowed us to cover a variety of shapes from negative to positive values of the mean and Gaussian curvature. We propose an analytical model to calculate the magnitude of the maximum out-of-plane deformation from the anisotropic expansion factor of the constituting microstructures. Furthermore, we develop computational models to predict the complex shape-changing of thermally actuated 4D printed structures given the distribution of rationally introduced imperfections and we demonstrate the potential applications of such defect-based metamaterials in drug delivery systems.

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.

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.

In orthopedic surgery, patient-specific bone plates are used for fixation when conventional bone plates do not fit the specific anatomy of a patient. However, plate failure can occur due to a lack of properly established design parameters that support optimal biomechanical properties of the plate. This review provides an overview of design parameters and biomechanical properties of patient-specific bone plates, which can assist in the design of the optimal plate. A literature search was conducted through PubMed and Embase, resulting in the inclusion of 78 studies, comprising clinical studies using patient-specific bone plates for fracture fixation or experimental studies that evaluated biomechanical properties or design parameters of bone plates. Biomechanical properties of the plates, including elastic stiffness, yield strength, tensile strength, and Poisson’s ratio are influenced by various factors, such as material properties, geometry, interface distance, fixation mechanism, screw pattern, working length and manufacturing techniques. Although variations within studies challenge direct translation of experimental results into clinical practice, this review serves as a useful reference guide to determine which parameters must be carefully considered during the design and manufacturing process to achieve the desired biomechanical properties of a plate for fixation of a specific type of fracture. Graphical Abstract: [Figure not available: see fulltext.]

Durable interfacing of hard and soft materials is a major design challenge caused by the ensuing stress concentrations. In nature, soft-hard interfaces exhibit remarkable mechanical performance, with failures rarely happening at the interface. Here, we mimic the strategies observed in nature to design efficient soft-hard interfaces. We base our geometrical designs on triply periodic minimal surfaces (i.e., Octo, Diamond, and Gyroid), collagen-like triple helices, and randomly distributed particles. A combination of computational simulations and experimental techniques, including uniaxial tensile and quad-lap shear tests, are used to characterize the mechanical performance of the interfaces. Our analyses suggest that smooth interdigitated connections, compliant gradient transitions, and either decreasing or constraining strain concentrations lead to simultaneously strong and tough interfaces. We generate additional interfaces where the abovementioned toughening mechanisms work synergistically to create soft-hard interfaces with strengths approaching the upper achievable limit and enhancing toughness values by 50%, as compared to the control group.

Orthopedic plates are commonly used after osteotomies for temporary fixation of bones. Patient-specific plates have recently emerged as a promising fixation device. However, it is unclear how various strategies used for the design of such plates perform in comparison with each other. Here, we compare the biomechanical performance of 3D printed patient-specific bone plates designed using conventional computer-aided design (CAD) techniques with those designed with the help of topology optimization (TO) algorithms, focusing on cases involving slipped capital femoral epiphysis (SCFE). We established a biomechanical testing protocol to experimentally assess the performance of the designed plates while measuring the full-field strain using digital image correlation. We also created an experimentally validated finite element model to analyze the performance of the plates under physiologically relevant loading conditions. The results indicated that the TO construct exhibited higher ultimate load and biomechanical performance as compared to the CAD construct, suggesting that TO is a viable approach for the design of such patient-specific bone plates. The TO plate also distributed stress more evenly over the screws, likely resulting in more durable constructs and improved anatomical conformity while reducing the risk of screw and plate failure during cyclic loading. Although differences existed between finite element analysis and experimental testing, this study demonstrated that finite element modelling can be used as a reliable method for evaluating and optimizing plates for SCFE patients. In addition to enhancing the mechanical performance of patient-specific fixation plates, the utilization of TO in plate design may also improve the surgical outcome and decrease the recovery time by reducing the plate and incision sizes.

Additive manufacturing (AM, also known as 3D printing) is an advanced manufacturing technique that has enabled progress in the design and fabrication of customised or patient-specific (meta-)biomaterials and biomedical devices (e.g., implants, prosthetics, and orthotics) with complex internal microstructures and tuneable properties. In the past few decades, several design guidelines have been proposed for creating porous lattice structures, particularly for biomedical applications. Meanwhile, the capabilities of AM to fabricate a wide range of biomaterials, including metals and their alloys, polymers, and ceramics, have been exploited, offering unprecedented benefits to medical professionals and patients alike. In this review article, we provide an overview of the design principles that have been developed and used for the AM of biomaterials as well as those dealing with three major categories of biomaterials, i.e., metals (and their alloys), polymers, and ceramics. The design strategies can be categorised as: library-based design, topology optimisation, bio-inspired design, and meta-biomaterials. Recent developments related to the biomedical applications and fabrication methods of AM aimed at enhancing the quality of final 3D-printed biomaterials and improving their physical, mechanical, and biological characteristics are also highlighted. Finally, examples of 3D-printed biomaterials with tuned properties and functionalities are presented.

4D printing of flat sheets that self-fold into architected 3D structures is a powerful origami-inspired approach for the fabrication of multi-functional devices and metamaterials. However, the opposite stiffness requirements for the folding process and the subsequent loadbearing of 3D structures impose an intrinsic limitation in designing self-folding metamaterials: while a low stiffness is required for the successful completion of the self-folding step, a high stiffness is needed for utilizing the folded structure as a load-bearing mechanical metamaterial. Here, we present a nonlinear analytical model of self-folding bilayer constructs composed of an active and passive layer. This finite-deformation theoretical model predicts the curvature of activated bilayers, establishes their stability limits, and estimates the stiffness of folded bilayers, yielding the theoretical stiffness limits of self-folding bilayers. We use our model to identify the optimal combinations of geometrical and mechanical properties that result in the highest possible stiffness of folded constructs. We then compare the predictions of our analytical model with computational results, and validate our theory with experimental realizations of 4D printed structures. Finally, we evaluate the theoretical stiffness limits of bilayer constructs made using the most common types of stimuli-responsive materials. Our analysis shows that a maximum effective modulus of ≈ 1.5 GPa can be achieved using the currently available shape-memory polymers.

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.