The rational design of bone-substituting biomaterials is relatively complex because they should meet a long list of requirements for optimal performance. Meta-biomaterials are micro-architected materials that hold great promise for meeting those requirements as they offer a unique combination of mechanical, mass-transport, and biological properties. There are, however, inherent couplings between the different types of properties of many such materials that make it impossible to simultaneously achieve all the design criteria. An example of such a coupling exists between the mechanical properties and the surface area. Strut-based, metallic meta-biomaterials are known to offer bone-mimicking mechanical properties, but they have limited surface area for cell adherence. Increasing the surface generally results in an undesirable increase in the mechanical properties that could lead to stress shielding. Here, we combine strut-based lattices with minimal surfaces to decouple these two properties. We added minimal surface patches to the designs of both auxetic and non-auxetic meta-biomaterials while minimizing their contribution to the mechanical properties of the resulting meta-biomaterials through the rational application of cuts or “slits”. All designs were additively manufactured using selective laser melting and mechanically tested to obtain their quasi-static mechanical properties, including their Poisson's ratio, in two configurations. A finite element-based computational homogenization code was used to compute the elastic moduli and anisotropy of the structures. The results show that the minimal surface patches substantially increase the available surface area without significantly affecting the mechanical properties. Without the slits, the surfaces significantly affected the elastic modulus and deformation behavior of the meta-biomaterials. A similar strategy could be used to tune the biodegradation rate of biodegradable metals and the permeability of meta-biomaterials in general.

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Since the beginning of time, humans have been trying to replace the skeletal system in cases of trauma or disease. Medical devices were designed, manufactured, and implanted, to restore the function of the skeletal system. Fast forward to today and joint replacements are among the most common surgeries carried out in the world. Despite their success, a relatively large number of patients will eventually need a revision surgery. In most cases, the implant fails due to aseptic loosening. Aseptic loosening represents a range of implant loosening cases not associated with infection and is often linked to an inflammatory response. This kind of implant loosening is often associated with the mechanical failure of the load-bearing connection at the bone-implant interface, which could be caused by inadequate initial fixation, the loss of fixation over time, or bone tissue deterioration as a result of (wear) particles. The complexity of the bony tissue, with its hierarchical and anisotropic structure, complicates the development of life-lasting replacements. Metallic biomaterials have been introduced as promising bone substitutes but their stiffness is usually vastly higher than that of the native bone. As a result, the patient’s bone becomes shielded from mechanical stimuli (stress shielding). Prolonged reduction in the mechanical stimuli results in bone resorption and may cause implant loosening. With the introduction of additively manufactured (AM) porous structures, the mechanical properties of metallic biomaterials could be reduced to the level of the bony tissue. Additionally, porous biomaterials allow for the diffusion of nutrients and oxygen, the ingrowth of de novo bone tissue, and the formation of capillaries. While this may sound as the golden combination, close bone-implant contact is of critical importance and can only be guaranteed if the implant matches the patient’s anatomy. Recent advances in AM have enabled the development of patient-specific implants, but this does not necessarily guarantee a lasting fixation. In the most ideal situation, the geometry of the implant should be tailored at both micro- and macroscale to optimize both shape-matching and material properties of the porous structures. This often calls for an unusual set of properties and functionalities that are not usually found in nature. Materials of which the small-scale architecture can be designed to obtain certain mechanical, mass-transport, and biological properties are referred to as meta-biomaterials. The deformation of a material in directions perpendicular to the direction of loading is described by the Poisson’s ratio. A negative value would indicate that the material exhibits lateral expansion in response to axial tension, which can be observed in auxetic materials. This Poisson effect is usually guided by the internal structure of the material, or the micro-architecture of meta-biomaterials. Changing the building block (i.e., the unit cell) will, therefore, change the micro-architecture and, thus, the deformation behavior of the material as a whole... @en

The fatigue performance of additively manufactured auxetic meta-biomaterials made from commercially pure titanium has been studied only recently. While certain assumptions have been made regarding the mechanisms underlying their fatigue failure, the exact mechanisms are not researched yet. Here, we studied the mechanisms of crack formation and propagation in cyclically loaded auxetic meta-biomaterials. Twelve different designs were subjected to compression-compression fatigue testing while performing full-field strain measurement using digital image correlation (DIC). The fatigue tests were stopped at different points before complete specimen failure to study the evolution of damage in the micro-architecture of the specimens using micro-computed tomography (micro-CT). Furthermore, finite element models were made to study the presence of stress concentrations. Structural weak spots were found in the inverted nodes and the vertical struts located along the outer rim of the specimens, matching the maximum principal strain concentrations and fracture sites in the DIC and micro-CT data. Cracks were often found to originate from internal void spaces or from sites susceptible to mode-I cracking. Many specimens maintained their structural integrity and exhibited no signs of rapid strain accumulation despite the presence of substantial crack growth. This observation underlines the importance of such microscale studies to identify accumulated damage that otherwise goes unnoticed. The potential release of powder particles from damaged lattices could elicit a foreign body response, adversely affecting the implant success. Finding the right failure criterion, therefore, requires more data than only those pertaining to macroscopic measurements and should always include damage assessment at the microscale. Statement of significance: The negative Poisson's ratio of auxetic meta-biomaterials makes them expand laterally in response to axial tension. This extraordinary property has great potential in the field of orthopedics, where it could enhance bone-implant contact. The fatigue performance of additively manufactured auxetic meta-biomaterials has only recently been studied and was found to be superior to many other bending- and stretch-dominated micro-architectures. In this study, we go beyond these macroscopic measurements and focus on the crack initiation and propagation. Full-field strain measurements and 3D imaging are used to paint a detailed picture of the mechanisms underlying fatigue. Using these data, specific aspects of the design and/or printing process can be targeted to improve the performance of auxetic meta-biomaterials in load-bearing applications.

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The unprecedented properties of meta-biomaterials could pave the way for the development of life-lasting orthopedic implants. Here, we used non-auxetic meta-biomaterials to address the shortcomings of the current treatment options in acetabular revision surgery. Due to the severe bone deficiencies and poor bone quality, it can be very challenging to acquire adequate initial implant stability and long-term fixation. More advanced treatments, such as patient-specific implants, do guarantee the initial stability, but are formidably expensive and may eventually fail due to stress shielding. We, therefore, developed meta-implants furnished with a deformable porous outer layer. Upon implantation, this layer plastically deforms into the defects, thereby improving the initial stability and homogeneously stimulating the surrounding bone. We first studied the space-filling behavior of additively manufactured pure titanium lattices, based on six different unit cells, in a compression test complemented with full-field strain measurements. The diamond, body-centered cubic, and rhombic dodecahedron unit cells were eventually selected for the design of the deformable porous outer layer. Each design came in three different relative density profiles, namely maximum (MAX), functionally graded (FG), and minimum (MIN). After their compression in bone-mimicking molds with simulated acetabular defects, the space-filling behavior of the implants was evaluated using load-displacement curves, micro-CT images, and 3D reconstructions. The meta-implants with an FG diamond infill exhibited the most promising space-filling behavior. However, the required push-in forces exceed the impact forces currently applied in surgery. Future research should, therefore, focus on design optimization, to improve the space-filling behavior and to facilitate the implantation process for orthopedic surgeons. Statement of significance: Ideally, orthopedic implants would last for the entire lifetime of the patient. Unfortunately, they rarely do. Critically sized defects are a common sight in the revision of acetabular cups, and rather difficult to treat. The permanent deformation of lattice structures can be used to create shape-morphing implants that would fill up the defect site, and thereby restore the physiological loading conditions. Bending-dominated structures were incorporated in the porous outer layer of the space-filling meta-implants for their considerable lateral expansion in response to axial compression. A functionally graded density offered structural integrity at the joint while enhancing the deformability at the bone-implant interface. With the use of a more ductile metal, CP-Ti, these meta-implants could be deformed without strut failure.

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Meta-biomaterials offer a promising route towards the development of life-lasting implants. The concept aims to achieve solutions that are ordinarily impossible, by offering a unique combination of mechanical, mass transport, and biological properties through the optimization of their small-scale geometrical and topological designs. In this study, we primarily focus on auxetic meta-biomaterials that have the extraordinary ability to expand in response to axial tension. This could potentially improve the longstanding problem of implant loosening, if their performance can be guaranteed in cyclically loaded conditions. The high-cycle fatigue performance of additively manufactured (AM) auxetic meta-biomaterials made from commercially pure titanium (CP-Ti) was therefore studied. Small variations in the geometry of the re-entrant hexagonal honeycomb unit cell and its relative density resulted in twelve different designs (relative density: ~5–45%, re-entrant angle = 10–25°, Poisson's ratio = -0.076 to -0.504). Micro-computed tomography, scanning electron microscopy and mechanical testing were used to respectively measure the morphological and quasi-static properties of the specimens before proceeding with compression-compression fatigue testing. These auxetic meta-biomaterials exhibited morphological and mechanical properties that are deemed appropriate for bone implant applications (elastic modulus = 66.3–5648 MPa, yield strength = 1.4–46.7 MPa, pore size = 1.3–2.7 mm). With an average maximum stress level of 0.47 σ_y at 10⁶ cycles (range: 0.35 σ_yσ_y- 0.82 σ_yσ_y), the auxetic structures characterized here are superior to many other non-auxetic meta-biomaterials made from the same material. The optimization of the printing process and the potential application of post-processing treatments could improve their performance in cyclically loaded settings even further. Statement of Significance: Auxetic meta-biomaterials have a negative Poisson's ratio and, therefore, expand laterally in response to axial tension. Recently, they have been found to restore bone-implant contact along the lateral side of a hip stem. As a result, the bone will be compressed along both of the implant's contact lines, thereby actively reducing the risk of implant failure. In this case the material will be subjected to cyclic loading, for which no experimental data has been reported yet. Here, we present the first ever study of the fatigue performance of additively manufactured auxetic meta-biomaterials based on the re-entrant hexagonal honeycomb. These results will advance the adoption of auxetic meta-biomaterials in load-bearing applications, such as the hip stem, to potentially improve implant longevity.

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The management of large acetabular defects remains one of the most challenging aspects of revision total hip arthroplasties. Failure of frequently used acetabular reconstruction components are, among others, caused by the lack of biological fixation, a non-physiological stress distribution and stress-shielding. Attempting to diminish these drawbacks of current implants a new acetabular cup has been explored. The double layer of this new acetabular cup better fills the acetabular defect. According to Wolff’s law this should reduce stress shielding and stimulate bone ingrowth. Part one of this study explores the relationship between unit cell size of the titanium and mechanical properties for the body centred cubic unit cell. Three graded lattices using different unit cell sizes were designed and 3D-printed out of commercially pure titanium (Grade 1) using selective laser melting. An unconfined compression test with cylindrical samples as well as a confined compression test with hemispherical samples were performed to obtain mechanical properties. An additional finite element study was used to validate the confined compression test. Acetabular defects were made in five Sawbones hemipelves which served as the basis for the design of the ‘patient specific’ acetabular cups. Three triflange and two unflanged acetabular cups were designed and 3D-printed out of commercially pure titanium (Grade 1) using selective laser melting. Mechanical properties were obtained from the unconfined compression tests. All acetabular cups were inserted by two orthopaedic surgeons at the UMC Utrecht. Cyclic testing was performed up to 1000 cycles to assess femoral head penetration under load after insertion. Additional penetration of the femoral head was found to be between 0.1781 and 0.3793 mm. Future work is needed to prevent strut breakage upon insertion and more research is needed in the fatigue behaviour of these new cups and their biological effect on living bone tissue.

The innovative design of orthopedic implants could play an important role in the development of life-lasting implants, by improving both primary and secondary implant fixations. The concept of meta-biomaterials aims to achieve a unique combination of mechanical, mass transport, and biological properties through optimized topological design of additively manufactured (AM) porous biomaterials. In this study, we primarily focused on a specific class of meta-biomaterials, namely auxetic meta-biomaterials. Their extraordinary behavior of lateral expansion in response to axial tension could potentially improve implant-bone contact in certain orthopedic applications. In this work, a multitude of auxetic meta-biomaterials were rationally designed and printed from Ti–6Al–4V using a commercially available laser powder bed fusion process called selective laser melting. The re-entrant hexagonal honeycomb unit cell was used as a starting point, which was then parametrically tuned to obtain a variety of mechanical and morphological properties. In this two-step study, the morphology and quasi-static properties of the developed meta-biomaterials were assessed using mechanical experiments accompanied with full-field strain measurements using digital image correlation. In addition, all our designs were computationally modelled using the finite element method. Our results showed the limits of the AM processes for the production of auxetic meta-biomaterials in terms of which values of the design parameters (e.g., re-entrant angle, relative density, and aspect ratio) could be successfully manufactured. We also found that the AM process itself imparts significant influence on the morphological and mechanical properties of the resulting auxetic meta-biomaterials. This further highlights the importance of experimental studies to determine the actual mechanical properties of such metamaterials. The elastic modulus and strength of many of our designs fell within the range of those reported for both trabecular and cortical bone. Unprecedented properties like these could be used to simultaneously address the different challenges faced in the mechanical design of orthopedic implants.

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Bone tissue engineering (BTE) researches the characteristics which are needed to create the ultimate bone scaffold which enhances cell response. Limited research has been done regarding the effect of the Poisson’s ratio on the scaffold-cell interaction. In this graduation project we therefore explore the cell response on scaffolds with a different value of the Poisson’s ratio. Various meta-biomaterials were designed, manufactured, mechanically tested and the response on pre-osteoblasts (MC3T3-E1) was explored. The first experiment was performed at mesoscale. The meta-biomaterials, with cells, were evaluated with SEM imaging, presto blue and ARS staining. The second experiment was performed at micro-scale. The results of this experiment were evaluated with SEM imaging, actin staining and Runx2 staining. It was concluded that the auxetic meta-biomaterial, with negative Poisson’s ratio, high porosity and high stiffness, showed an enhancement of the cell response. However, this could not be confirmed by the 2D SEM images. A potential application for the meta-biomaterial that enhances the cell response is implementing this meta-biomaterial in a design for the surface of an implant to generate fast bone ingrowth.

An acetabular revision is a very challenging intervention, due to moderate to severe bone deficiencies and poor bone quality. Current solutions for this intervention are associated with inconsistent and unreliable clinical outcomes. This leads to substantial complications, including implant migration and loosening. These complications are, among others, caused by the lack of biological fixation, a non-physiological stress distribution and stress shielding. To encounter these problems a novel concept for an acetabular revision has been presented. The aim of this new design is to plastically deform into massive acetabular bone deficiencies. This will stimulate the surrounding bone and therefore diminishes effect of stress shielding (Wolff’s Law). This study explored whether a porous layer made of pure titanium can achieve this space-filling behaviour. The infill of this porous layer is based on meta-biomaterials. The macro-scale properties of this type of materials are determined by their small-scale architecture. The aim of the first part of this study was therefore to systematically study the topology-property relationship of six topological designs, including the cube, truncated cube, truncated cuboctahedron, rhombic dodecahedron, diamond and body centred cubic. These designs were studied by experimentally determining their mechanical properties, including the Poisson’s ratio using the Digital Image Correlation (DIC) technique. Afterwards, three topological designs were selected to be implemented in the novel acetabular component, including the diamond, rhombic dodecahedron and body centred cubic. These unit cells showed the lowest stiffness and the highest positive Poisson’s ratio over the complete range of concerned porosities (80-98%). Besides, they showed bending-dominated deformation without the failure of struts. The results indicated that these unit cells have the highest capacity to plastically deform as well have the potential of space-filling behaviour. The porosity of the porous layer of the implant functionally graded from very porous at the bone-implant interface to very solid at the joint’s articulating surface, which corresponds to bone’s hierarchical structure. These implants were compressed inside a bone-mimicking mould, of which the appearance and mechanics resembled an acetabulum with large bone deficiencies. µCT images revealed that the implant based on the diamond unit cell showed the most promising deformability at the mould-implant interface. Although this deformation was promising, the push-in forces needed to compress the implant into the mould were very high (ranging from 3.33 kN to 14.8 kN). Future work is needed to diminish the need for these high push-in forces by making the porous outer layer even more deformable. This novel implant has the potential to increase the biological fixation, preserve the physiological stress distribution and diminish the effect of stress shielding in the acetabular component of a total hip replacement.

Cavitary bone defects are common in orthopedic surgery and may be present after curettage of benign tumors or as tumor-like lesions. Bone graft substitutes, especially from biocompatible materials, can be used as a solution for lling up those defects. However, these cavitary bone defects differ in size and
location. It would, therefore, be convenient to utilize an implant that can change its shape according to its surrounding 3D environment, meaning there is no need to customize the implant for every patient case. In the last decade, additive manufacturing (AM) techniques have been the driving force behind the fabrication of complex three-dimensional objects. The various assets of these procedures enable the production of very complex designs with appropriate material properties. These materials that are engineered to exhibit certain properties are referred to as meta-materials. Functionalizing these materials on a nano-scale, to have certain biological or mass transport properties brings us to a new class of materials better known as meta-biomaterials. In this regard, highly deformable implants with novel properties can be referred to as meta-biomechanisms, consisting of multiple interconnected joints. The current research revolves around the direct fabrication of meta-biomechanisms using Selective Laser Melting (SLM). Subsequently, the general design recommendations and process constraints have been discussed briefly for the fabrication of mechanisms using SLM. In this regard, SLM poses an extra burden on the removal of supports, especially for the vulnerable geometries and within the joints clearance. Implementing a design approach, including both systematic and intuitive methods, was chosen as
the main tool towards the accomplishment of the research aim. Consequently, new designs are proposed to minimize these undesirable events and the supports, with the subsequent challenge to obtain multi-joint mechanisms with increased Degrees of Freedom (DOF) and the least amount of supports. The rst joints have been successfully printed, as well as meshes of multiple joints. Surface Morphing Experiments were nally executed to classify them in terms of motion, taking into account the nal application. According to the results, the majority of the proposed meta- biomechanisms approach well the reference acetabular model, with an absolute difference below 1, reassuring the possibility of the proposed meta-biomechanisms as potential implants in cavitary bone defects. Besides the evaluation in terms of mobility, the structures were mechanically tested to derive their behavior under compression loading. The force needed to induce a sharp break was lower than the average peak force reported in hip joints during daily activities. Subsequently, the experiments revealed that their mechanical strength depends on the tting of the structures inside the acetabulum model. The bigger the gap between the structure and the acetabulum, the weaker the structure under compression loading. Overall, their scale and size should be optimized to sustain the average day-to-day forces joints are subjected to.

The concept of "mechanical metamaterials" has become increasingly popular, since their macro-scale characteristics can be designed to exhibit unusual combinations of mechanical properties on the micro-scale. The advances in additive manufacturing (AM, three-dimensional printing) techniques have boosted the fabrication of these mechanical metamaterials by facilitating a precise control over their micro-architecture. Although mechanical metamaterials with negative Poisson's ratios (i.e., auxetic metamaterials) have received much attention before and have been reviewed multiple times, no comparable review exists for architected materials with positive Poisson's ratios. Therefore, this review will focus on the topology-property relationships of non-auxetic mechanical metamaterials in general and five topological designs in particular. These include the designs based on the diamond, cube, truncated cube, rhombic dodecahedron, and the truncated cuboctahedron unit cells. We reviewed the mechanical properties and fatigue behavior of these architected materials, while considering the effects of other factors such as those of the AM process. In addition, we systematically analyzed the experimental, computational, and analytical data and solutions available in the literature for the titanium alloy Ti-6Al-4V. Compression dominated lattices, such as the (truncated) cube, showed the highest mechanical properties. All of the proposed unit cells showed a normalized fatigue strength below that of solid titanium (i.e., 40% of the yield stress), in the range of 12-36% of their yield stress. The unit cells discussed in this review could potentially be applied in bone-mimicking porous structures.

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Microstructures with spatially-varying properties such as trabecular bone are widely seen in nature. These functionally graded materials possess smoothly changing microstructural topologies that enable excellent micro and macroscale performance. The fabrication of such microstructural materials is now enabled by additive manufacturing (AM). A challenging aspect in the computational design of such materials is ensuring compatibility between adjacent microstructures. Existing works address this problem by ensuring geometric connectivity between adjacent microstructural unit cells. In this paper, we aim to find the optimal connectivity between topology optimized microstructures. Recognizing the fact that the optimality of connectivity can be evaluated by the resulting physical properties of the assemblies, we propose to consider the assembly of adjacent cells together with the optimization of individual cells. In particular, our method simultaneously optimizes the physical properties of the individual cells as well as those of neighbouring pairs, to ensure material connectivity and smoothly varying physical properties. We demonstrate the application of our method in the design of functionally graded materials for implant design (including an implant prototype made by AM), and in the multiscale optimization of structures.

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