4D (bio‐)printing endows 3D printed (bio‐)materials with multiple functionalities and dynamic properties. 4D printed materials have been recently used in biomedical engineering for the design and fabrication of biomedical devices, such as stents, occluders, microneedles, smart 3D‐cell engineered microenvironments, drug delivery systems, wound closures, and implantable medical devices. However, the success of 4D printing relies on the rational design of 4D printed objects, the selection of smart materials, and the availability of appropriate types of external (multi‐)stimuli. Here, this work first highlights the different types of smart materials, external stimuli, and design strategies used in 4D (bio‐)printing. Then, it presents a critical review of the biomedical applications of 4D printing and discusses the future directions of biomedical research in this exciting area, including in vivo tissue regeneration studies, the implementation of multiple materials with reversible shape memory behaviors, the creation of fast shape‐transformation responses, the ability to operate at the microscale, untethered activation and control, and the application of (machine learning‐based) modeling approaches to predict the structure–property and design–shape transformation relationships of 4D (bio)printed constructs.

The growing interest in multi-functional metallic biomaterials for bone substitutes challenges the current additive manufacturing (AM, =3D printing) technologies. It is foreseeable that advances in multi-material AM for metallic biomaterials will not only allow for complex geometrical designs, but also improve their multi-functionalities by tuning the types or compositions of the underlying base materials, thereby presenting unprecedented opportunities for advanced orthopedic treatments. AM technologies are yet to be extensively explored for the fabrication of multi-functional metallic biomaterials, especially for bone substitutes. The aim of this review is to present the viable options of the state-of-the-art multi-material AM for Ti-, Mg-, and Fe-based biomaterials to be used as bone substitutes. The review starts with a brief review of bone tissue engineering, the design requirements, and fabrication technologies for metallic biomaterials to highlight the advantages of using AM over conventional fabrication methods. Five AM technologies suitable for metal 3D printing are compared against the requirements for multi-material AM. Of these AM technologies, extrusion-based multi-material AM is shown to have the greatest potential to meet the requirements for the fabrication of multi-functional metallic biomaterials. Finally, recent progress in the fabrication of Ti-, Mg-, and Fe-based biomaterials including the utilization of multi-material AM technologies is reviewed so as to identify the knowledge gaps and propose the directions of further research for the development of multi-material AM technologies that are applicable for the fabrication of multi-functional metallic biomaterials. STATEMENT OF SIGNIFICANCE: Addressing a critical bone defect requires the assistance of multi-functional porous metallic bone substitutes. As one of the most advanced fabrication technology in bone tissue engineering, additive manufacturing is challenged for its viability in multi-material fabrication of metallic biomaterials. This article reviews how the current metal additive manufacturing technologies have been and can be used for multi-material fabrication of Ti-, Mg-, and Fe-based bone substitutes. Progress on the Ti-, Mg-, and Fe-based biomaterials, including the utilization of multi-material additive manufacturing, are discussed to direct future research for advancing the multi-functional additively manufactured metallic bone biomaterials.

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.

Architectured materials with rationally designed geometries could be used to create mechanical metamaterials with unprecedented or rare properties and functionalities. Here, we introduce “shape-matching” metamaterials where the geometry of cellular structures comprising auxetic and conventional unit cells is designed so as to achieve a pre-defined shape upon deformation. We used computational models to forward-map the space of planar shapes to the space of geometrical designs. The validity of the underlying computational models was first demonstrated by comparing their predictions with experimental observations on specimens fabricated with indirect additive manufacturing. The forward-maps were then used to devise the geometry of cellular structures that approximate the arbitrary shapes described by random Fourier’s series. Finally, we show that the presented metamaterials could match the contours of three real objects including a scapula model, a pumpkin, and a Delft Blue pottery piece. Shape-matching materials have potential applications in soft robotics and wearable (medical) devices.

Up until recently, the rational design of mechanical metamaterials has usually involved devising geometrical arrangements of micro-architectures that deliver unusual properties on the macro-scale. A less explored route to rational design is spatially distributing materials with different properties within lattice structures to achieve the desired mechanical properties. Here, we used computational models and advanced multi-material 3D printing techniques to rationally design and additively manufacture multi-material cellular solids for which the elastic modulus and Poisson's ratio could be independently tailored in different (anisotropic) directions. The random assignment of a hard phase to originally soft cellular structures with an auxetic, zero Poisson's ratio, and conventional designs allowed us to cover broad regions of the elastic modulus-Poisson's ratio plane. Patterned designs of the hard phase were also used and were found to be effective in the independent tuning of the elastic properties. Close inspection of the strain distributions associated with the different types of material distributions suggests that locally deflected patterns of deformation flow and strain localizations are the main underlying mechanisms driving the above-mentioned adjustments in the mechanical properties.