Microfluidic Tissue Engineering and Bio-Actuation

Bio-hybrid technologies aim to replicate the unique capabilities of biological systems that could surpass advanced artificial technologies. Soft bio-hybrid robots consist of synthetic and living materials and have the potential to self-assemble, regenerate, work autonomously, and interact safely with other species and the environment. Cells require a sufficient exchange of nutrients and gases, which is guaranteed by convection and diffusive transport through liquid media. The functional development and long-term survival of biological tissues in vitro can be improved by dynamic flow culture, but only microfluidic flow control can develop tissue with fine structuring and regulation at the microscale. Full control of tissue growth at the microscale will eventually lead to functional macroscale constructs, which are needed as the biological component of soft bio-hybrid technologies. This review summarizes recent progress in microfluidic techniques to engineer biological tissues, focusing on the use of muscle cells for robotic bio-actuation. Moreover, the instances in which bio-actuation technologies greatly benefit from fusion with microfluidics are highlighted, which include: the microfabrication of matrices, biomimicry of cell microenvironments, tissue maturation, perfusion, and vascularization.ISSN:0935-9648ISSN:1521-409

Will microfluidics enable functionally integrated biohybrid robots?

The next robotics frontier will be led by biohybrids. Capable biohybrid robots require microfluidics to sustain, improve, and scale the architectural complexity of their core ingredient: biological tissues. Advances in microfluidics have already revolutionized disease modeling and drug development, and are positioned to impact regenerative medicine but have yet to apply to biohybrids. Fusing microfluidics with living materials will improve tissue perfusion and maturation, and enable precise patterning of sensing, processing, and control elements. This perspective suggests future developments in advanced biohybrids.ISSN:0027-8424ISSN:1091-649

Engineered Magnetic Nanocomposites to Modulate Cellular Function

Magnetic nanoparticles (MNPs) have various applications in biomedicine, including imaging, drug delivery and release, genetic modification, cell guidance, and patterning. By combining MNPs with polymers, magnetic nanocomposites (MNCs) with diverse morphologies (core-shell particles, matrix-dispersed particles, microspheres, etc.) can be generated. These MNCs retain the ability of MNPs to be controlled remotely using external magnetic fields. While the effects of these biomaterials on the cell biology are still poorly understood, such information can help the biophysical modulation of various cellular functions, including proliferation, adhesion, and differentiation. After recalling the basic properties of MNPs and polymers, and describing their coassembly into nanocomposites, this review focuses on how polymeric MNCs can be used in several ways to affect cell behavior. A special emphasis is given to 3D cell culture models and transplantable grafts, which are used for regenerative medicine, underlining the impact of MNCs in regulating stem cell differentiation and engineering living tissues. Recent advances in the use of MNCs for tissue regeneration are critically discussed, particularly with regard to their prospective involvement in human therapy and in the construction of advanced functional materials such as magnetically operated biomedical robots.ISSN:1613-6810ISSN:1613-682

Perfusable Biohybrid Designs for Bioprinted Skeletal Muscle Tissue

Engineered, centimeter-scale skeletal muscle tissue (SMT) can mimic muscle pathophysiology to study development, disease, regeneration, drug response, and motion. Macroscale SMT requires perfusable channels to guarantee cell survival, and support elements to enable mechanical cell stimulation and uniaxial myofiber formation. Here, stable biohybrid designs of centimeter-scale SMT are realized via extrusion-based bioprinting of an optimized polymeric blend based on gelatin methacryloyl and sodium alginate, which can be accurately coprinted with other inks. A perfusable microchannel network is designed to functionally integrate with perfusable anchors for insertion into a maturation culture template. The results demonstrate that i) coprinted synthetic structures display highly coherent interfaces with the living tissue, ii) perfusable designs preserve cells from hypoxia all over the scaffold volume, iii) constructs can undergo passive mechanical tension during matrix remodeling, and iv) the constructs can be used to study the distribution of drugs. Extrusion-based multimaterial bioprinting with the inks and design realizes in vitro matured biohybrid SMT for biomedical applications.ISSN:2192-2640ISSN:2192-265

An Overview of Soft Robotics

Soft robots’ flexibility and compliance give them the potential to outperform traditional rigid-bodied robots while performing multiple tasks in unexpectedly changing environments and conditions. However, soft robots have not yet revealed their full potential since nature is still far more advanced in several areas, such as locomotion and manipulation. To understand what limits their performance and hinders their transition from laboratory to real-world conditions, future studies should focus on understanding the principles behind the design and operation of soft robots. Such studies should also consider the major challenges with regard to complex materials, accurate modeling, advanced control, and intelligent behaviors. As a starting point for such studies, this review provides a current overview of the field by examining the working mechanisms of advanced actuation and sensing modalities, modeling techniques, control strategies, and learning architectures for soft robots. Next, we summarize how these approaches can be applied to create sophisticated soft robots and examine their application areas. Finally, we provide future perspectives on what key challenges should be tackled first to advance soft robotics to truly add value to our society. Expected final online publication date for the Annual Review of Control, Robotics, and Autonomous Systems, Volume 14 is May 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.ISSN:2573-514

Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery

Bacterial biohybrids, composed of self-propelling bacteria carrying micro/nanoscale materials, can deliver their payload to specific regions under magnetic control, enabling additional frontiers in minimally invasive medicine. However, current bacterial biohybrid designs lack high-throughput and facile construction with favorable cargoes, thus underperforming in terms of propulsion, payload efficiency, tissue penetration, and spatiotemporal operation. Here, we report magnetically controlled bacterial biohybrids for targeted localization and multistimuliresponsive drug release in three-dimensional (3D) biological matrices. Magnetic nanoparticles and nanoliposomes loaded with photothermal agents and chemotherapeutic molecules were integrated onto Escherichia coli with ~90% efficiency. Bacterial biohybrids, outperforming previously reported E. coli–based microrobots, retained their original motility and were able to navigate through biological matrices and colonize tumor spheroids under magnetic fields for on-demand release of the drug molecules by near-infrared stimulus. Our work thus provides a multifunctional microrobotic platform for guided locomotion in 3D biological networks and stimuli-responsive delivery of therapeutics for diverse medical applications.ISSN:2375-254

Hydroelastomers: soft, tough, highly swelling composites

Inspired by the cellular design of plant tissue, we present an approach to make versatile, tough, highly water-swelling composites. We embed highly swelling hydrogel particles inside tough, water-permeable, elastomeric matrices. The resulting composites, which we call hydroelastomers, combine the properties of their parent phases. From their hydrogel component, the composites inherit the ability to highly swell in water. From the elastomeric component, the composites inherit excellent stretchability and fracture toughness, while showing little softening as they swell. Indeed, the fracture properties of the composite match those of the best-performing, tough hydrogels, exhibiting fracture energies of up to 10 kJ m(-2). Our composites are straightforward to fabricate, based on widely-available materials, and can easily be molded or extruded to form shapes with complex swelling geometries. Furthermore, there is a large design space available for making hydroelastomers, since one can use any hydrogel as the dispersed phase in the composite, including hydrogels with stimuli-responsiveness. These features make hydroelastomers excellent candidates for use in soft robotics and swelling-based actuation, or as shape-morphing materials, while also being useful as hydrogel replacements in other fields.ISSN:1744-683XISSN:1744-684