The ethics of engineered living materials.

Engineered living materials (ELMs) combine living and non-living entities. Their associated ethical concerns must be addressed to promote safety, promote sustainability, and regulate societal impacts. This article identifies key ethical and safety issues by reflecting on fundamental ethical principles. It further discusses a future ethical roadmap for sustainable research in ELMs.

Microarchitected Compliant Scaffolds of Pyrolytic Carbon for 3D Muscle Cell Growth.

The integration of additive manufacturing technologies with the pyrolysis of polymeric precursors enables the design-controlled fabrication of architected 3D pyrolytic carbon (PyC) structures with complex architectural details. Despite great promise, their use in cellular interaction remains unexplored. This study pioneers the utilization of microarchitected 3D PyC structures as biocompatible scaffolds for the colonization of muscle cells in a 3D environment. PyC scaffolds are fabricated using micro-stereolithography, followed by pyrolysis. Furthermore, an innovative design strategy using revolute joints is employed to obtain novel, compliant structures of architected PyC. The pyrolysis process results in a pyrolysis temperature- and design-geometry-dependent shrinkage of up to 73%, enabling the geometrical features of microarchitected compatible with skeletal muscle cells. The stiffness of architected PyC varies with the pyrolysis temperature, with the highest value of 29.57 ± 0.78 GPa for 900 °C. The PyC scaffolds exhibit excellent biocompatibility and yield 3D cell colonization while culturing skeletal muscle C2C12 cells. They further induce good actin fiber alignment along the compliant PyC construction. However, no conclusive myogenic differentiation is observed here. Nevertheless, these results are highly promising for architected PyC scaffolds as multifunctional tissue implants and encourage more investigations in employing compliant architected PyC structures for high-performance tissue engineering applications.

Artificial Intelligence Aided Ethics in Frontier Research.

Emergent technologies are frequently demonized due to the fear of the unknown. The doubts and alarms are more often than not sparked by their own developers, in a secret wish to become the masters of such fears, and thereby increase their control and influence upon laymen. The story is as old as the use of fire by the sorcerers guiding most ancient rituals. Now it seems to be the turn of artificial intelligence (AI), which is being continuously tainted with quasi-apocalyptic shadows, despite its remarkable potentials for supporting highly desirable societal transformations.

Ethical Issues of 4D Printed Medical Devices.

Since the dawn of additive manufacturing technologies in the 1980s and 90s, now commonly named 3D printing, the possibility of processing raw materials into freeform designed objects with unprecedented shape complexity opened new avenues for the development of medical devices. Indeed, the geometries of nature and the human body are extremely multifaceted, with even fractal- like or multiscale levels of detail, counting with functional gradients of properties, including topology and topography optimizations, to cite some interesting features. In consequence, classical subtracting manufacturing technologies, shape forming tools, and mass production chains are suboptimal for personalizing medical devices and adequately emulating life.

Toward a More Ethical and Sustainable Biomedical Engineering Education.

Important Lessons Can be learned from the COVID-19 pandemic, which after more than two years of worldwide suffering is still among us. First, we now better understand that global health concerns cannot be tackled and solved individually and verify that the dream for universal health care is far from being fulfilled. Besides, biomedical technologies and medical devices, despite their transformative potential, cannot always reach those urgently needing them, due to centralized production, supply chain issues, intellectual property restrictions, and lack of raw materials and resources close to the point of care, which calls for a renovation of the biomedical industry aimed at sustainability and equity. To make matters worse, unethical behaviors of governments, companies, and citizens, from which the ongoing pandemic has provided plenty of examples, also endanger the already challenging progress toward the Sustainable Development Goals (SDGs), including "Goal 3" on "Good Health and Well Being."

Biomedical Bauhaus: Utopian Dream or Health and Educational Breakthrough Digital Object.

Just before the COVID-19 pandemic, 2019 marked the 100th anniversary of the school and manifesto of the Bauhaus. Now that life is slowly returning to normal, it may be a good moment to celebrate one of the most transformative educational initiatives ever, with the motivation of developing a model that could also transform BME.

Carbon-Based Materials for Articular Tissue Engineering: From Innovative Scaffolding Materials toward Engineered Living Carbon.

Carbon materials constitute a growing family of high-performance materials immersed in ongoing scientific technological revolutions. Their biochemical properties are interesting for a wide set of healthcare applications and their biomechanical performance, which can be modulated to mimic most human tissues, make them remarkable candidates for tissue repair and regeneration, especially for articular problems and osteochondral defects involving diverse tissues with very different morphologies and properties. However, more systematic approaches to the engineering design of carbon-based cell niches and scaffolds are needed and relevant challenges should still be overcome through extensive and collaborative research. In consequence, this study presents a comprehensive description of carbon materials and an explanation of their benefits for regenerative medicine, focusing on their rising impact in the area of osteochondral and articular repair and regeneration. Once the state-of-the-art is illustrated, innovative design and fabrication strategies for artificially recreating the cellular microenvironment within complex articular structures are discussed. Together with these modern design and fabrication approaches, current challenges, and research trends for reaching patients and creating social and economic impacts are examined. In a closing perspective, the engineering of living carbon materials is also presented for the first time and the related fundamental breakthroughs ahead are clarified.

Carbon fiber/microlattice 3D hybrid architecture as multi-scale scaffold for tissue engineering.

Multiscale 3D carbon architectures are of particular interest in tissue engineering applications, as these structures may allow for three-dimensional cell colonization essential for tissue growth. In this work, carbon fiber/microlattice hybrid architectures are introduced as innovative multi-scale scaffolds for tissue engineering. The microlattice provides the design freedom and structural integrity, whereas the fibrous component creates a cellular microenvironment for cell colonization. The hybrid structures are fabricated by carbonization of stereolithographically 3D printed epoxy microlattice architectures which are pre-filled with cotton fibers within the empty space of the architectures. The cotton filling result in less shrinkage of the architecture during carbonization, as the tight confinement of the fibrous material prevents the free-shrinkage of the microlattices. The hybrid architecture exhibits a compressive strength of 156.9±25.6 kPa, which is significantly higher than an empty carbon microlattice architecture. Furthermore, the hybrid architecture exhibits a flexible behavior up to 30% compressive strain, which is also promising towards soft-tissue regeneration. Osteoblast-like murine MC3T3-E1 cells are cultured within the 3D hybrid structures. Results show that the cells are able to not only proliferate on the carbon microlattice elements as well as along the carbon fibers, but also make connections with each other across the inner pores created by the fibers, leading to a three-dimensional cell colonization. These carbon fiber/microlattice hybrid structures are promising for future fabrication of functionally graded scaffolds for tissue repair applications.

Lotus-on-chip: computer-aided design and 3D direct laser writing of bioinspired surfaces for controlling the wettability of materials and devices.

In this study we present the combination of a math-based design strategy with direct laser writing as high-precision technology for promoting solid free-form fabrication of multi-scale biomimetic surfaces. Results show a remarkable control of surface topography and wettability properties. Different examples of surfaces inspired on the lotus leaf, which to our knowledge are obtained for the first time following a computer-aided design with this degree of precision, are presented. Design and manufacturing strategies towards microfluidic systems whose fluid driving capabilities are obtained just by promoting a design-controlled wettability of their surfaces, are also discussed and illustrated by means of conceptual proofs. According to our experience, the synergies between the presented computer-aided design strategy and the capabilities of direct laser writing, supported by innovative writing strategies to promote final size while maintaining high precision, constitute a relevant step forward towards materials and devices with design-controlled multi-scale and micro-structured surfaces for advanced functionalities. To our knowledge, the surface geometry of the lotus leaf, which has relevant industrial applications thanks to its hydrophobic and self-cleaning behavior, has not yet been adequately modeled and manufactured in an additive way with the degree of precision that we present here.

Rapid prototyping of multi-scale biomedical microdevices by combining additive manufacturing technologies.

The possibility of designing and manufacturing biomedical microdevices with multiple length-scale geometries can help to promote special interactions both with their environment and with surrounding biological systems. These interactions aim to enhance biocompatibility and overall performance by using biomimetic approaches. In this paper, we present a design and manufacturing procedure for obtaining multi-scale biomedical microsystems based on the combination of two additive manufacturing processes: a conventional laser writer to manufacture the overall device structure, and a direct-laser writer based on two-photon polymerization to yield finer details. The process excels for its versatility, accuracy and manufacturing speed and allows for the manufacture of microsystems and implants with overall sizes up to several millimeters and with details down to sub-micrometric structures. As an application example we have focused on manufacturing a biomedical microsystem to analyze the impact of microtextured surfaces on cell motility. This process yielded a relevant increase in precision and manufacturing speed when compared with more conventional rapid prototyping procedures.

Towards Low-Cost Effective and Homogeneous Thermal Activation of Shape Memory Polymers.

A typical limitation of intelligent devices based on the use of shape-memory polymers as actuators is linked to the widespread use of distributed heating resistors, via Joule effect, as activation method, which involves several relevant issues needing attention, such as: (a) Final device size is importantly increased due to the additional space required for the resistances; (b) the use of resistances limits materials' strength and the obtained devices are normally weaker; (c) the activation process through heating resistances is not homogeneous, thus leading to important temperature differences among the polymeric structure and to undesirable thermal gradients and stresses, also limiting the application fields of shape-memory polymers. In our present work we describe interesting activation alternatives, based on coating shape-memory polymers with different kinds of conductive materials, including textiles, conductive threads and conductive paint, which stand out for their easy, rapid and very cheap implementation. Distributed heating and homogeneous activation can be achieved in several of the alternatives studied and the technical results are comparable to those obtained by using advanced shape-memory nanocomposites, which have to deal with complex synthesis, processing and security aspects. Different combinations of shape memory epoxy resin with several coating electrotextiles, conductive films and paints are prepared, simulated with the help of thermal finite element method based resources and characterized using infrared thermography for validating the simulations and overall design process. A final application linked to an active catheter pincer is detailed and the advantages of using distributed heating instead of conventional resistors are discussed.

Novel system for bite-force sensing and monitoring based on magnetic near field communication.

Intraoral devices for bite-force sensing have several applications in odontology and maxillofacial surgery, as bite-force measurements provide additional information to help understand the characteristics of bruxism disorders and can also be of help for the evaluation of post-surgical evolution and for comparison of alternative treatments. A new system for measuring human bite forces is proposed in this work. This system has future applications for the monitoring of bruxism events and as a complement for its conventional diagnosis. Bruxism is a pathology consisting of grinding or tight clenching of the upper and lower teeth, which leads to several problems such as lesions to the teeth, headaches, orofacial pain and important disorders of the temporomandibular joint. The prototype uses a magnetic field communication scheme similar to low-frequency radio frequency identification (RFID) technology (NFC). The reader generates a low-frequency magnetic field that is used as the information carrier and powers the sensor. The system is notable because it uses an intra-mouth passive sensor and an external interrogator, which remotely records and processes information regarding a patient's dental activity. This permits a quantitative assessment of bite-force, without requiring intra-mouth batteries, and can provide supplementary information to polysomnographic recordings, current most adequate early diagnostic method, so as to initiate corrective actions before irreversible dental wear appears. In addition to describing the system's operational principles and the manufacture of personalized prototypes, this report will also demonstrate the feasibility of the system and results from the first in vitro and in vivo trials.

Rapid prototyping for biomedical engineering: current capabilities and challenges.

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.