A new set of manufacturing technologies has emerged in the past decades to address market requirements in a customized way and to provide support for research tasks that require prototypes. These new techniques and technologies are usually referred to as rapid prototyping and manufacturing technologies, and they allow prototypes to be produced in a wide range of materials with remarkable precision in a couple of hours. Although they have been rapidly incorporated into product development methodologies, they are still under development, and their applications in bioengineering are continuously evolving. Rapid prototyping and manufacturing technologies can be of assistance in every stage of the development process of novel biodevices, to address various problems that can arise in the devices' interactions with biological systems and the fact that the design decisions must be tested carefully. This review focuses on the main fields of application for rapid prototyping in biomedical engineering and health sciences, as well as on the most remarkable challenges and research trends.

Auxetic metamaterials are characterized by a negative Poisson ratio (NPR) and display an unexpected property of lateral expansion when stretched and densification when compressed. Auxetic properties can be achieved by designing special microstructures, hence their classification as metamaterials, and can be manufactured with varied raw materials and methods. Since work in this field began, auxetics have been considered for different biomedical applications, as some biological tissues have auxetic-like behaviour due to their lightweight structure and morphing properties, which makes auxetics ideal for interacting with the human body. This research study is developed with the aim of presenting an updated overview of auxetic metamaterials for biomedical devices. It stands out for providing a comprehensive view of medical applications for auxetics, including a focus on prosthetics, orthotics, ergonomic appliances, performance enhancement devices, in vitro medical devices for interacting with cells, and advanced medicinal clinical products, especially tissue engineering scaffolds with living cells. Innovative design and simulation approaches for the engineering of auxetic-based products are covered, and the relevant manufacturing technologies for prototyping and producing auxetics are analysed, taking into consideration those capable of processing biomaterials and enabling multi-scale and multi-material auxetics. An engineering design rational for auxetics-based medical devices is presented with integrative purposes. Finally, key research, development and expected technological breakthroughs are discussed.

Design requirements for different mechanical metamaterials, porous constructions and lattice structures, employed as tissue engineering scaffolds, lead to multi-objective optimizations, due to the complex mechanical features of the biological tissues and structures they should mimic. In some cases, the use of conventional design and simulation methods for designing such tissue engineering scaffolds cannot be applied because of geometrical complexity, manufacturing defects or large aspect ratios leading to numerical mismatches. Artificial intelligence (AI) in general, and machine learning (ML) methods in particular, are already finding applications in tissue engineering and they can prove transformative resources for supporting designers in the field of regenerative medicine. In this study, the use of 3D convolutional neural networks (3D CNNs), trained using digital tomographies obtained from the CAD models, is validated as a powerful resource for predicting the mechanical properties of innovative scaffolds. The presented AI-aided or ML-aided design strategy is believed as an innovative approach in area of tissue engineering scaffolds, and of mechanical metamaterials in general. This strategy may lead to several applications beyond the tissue engineering field, as we analyze in the discussion and future proposals sections of the research study.