A soft, scalable and adaptable multi-contact cuff electrode for targeted peripheral nerve modulation.

BACKGROUND: Cuff electrodes target various nerves throughout the body, providing neuromodulation therapies for motor, sensory, or autonomic disorders. However, when using standard, thick silicone cuffs, fabricated in discrete circular sizes, complications may arise, namely cuff displacement or nerve compression, due to a poor adaptability to variable nerve shapes and sizes encountered in vivo. Improvements in cuff design, materials, closing mechanism and surgical approach are necessary to overcome these issues. METHODS: In this work, we propose a microfabricated multi-channel silicone-based soft cuff electrode with a novel easy-to-implant and size-adaptable design and evaluate a number of essential features such as nerve-cuff contact, nerve compression, cuff locking stability, long-term integration and stimulation selectivity. We also compared performance to that of standard fixed-size cuffs. RESULTS: The belt-like cuff made of 150 µm thick silicone membranes provides a stable and pressure-free conformal contact, independently of nerve size variability, combined with a straightforward implantation procedure. The adaptable design and use of soft materials lead to limited scarring and demyelination after 6-week implantation. In addition, multi-contact designs, ranging from 6 to 16 electrodes, allow for selective stimulation in models of rat and pig sciatic nerve, achieving targeted activation of up to 5 hindlimb muscles. CONCLUSION: These results suggest a promising alternative to classic fixed-diameter cuffs and may facilitate the adoption of soft, adaptable cuffs in clinical settings.

Microfluidic-assisted bioprinting of tissues and organoids at high cell concentrations.

Despite its simplicity, which makes it the most commonly used bioprinting method today, extrusion-based bioprinting suffers from its inability to reproduce the complex tissue architecture found in organs. Generally, this printing method allows for the dispensing of solutions of a predefined cell concentration through a rudimentary needle. Moreover, to avoid cell lysis in the dispensing needle, which is detrimental to the viability of the printed tissue, as well as cell loss in dead volumes of tubing, thereby increasing the cost of printing tissue, a common strategy has been to print with cell concentrations much lower in comparison to the concentrations found in living tissues. As a result, cell-to-cell distance is increased in the dispensed samples impairing communication through cytokines. Here, we present a microfluidic-based print head capable of modulating the printed cell concentration in real-time. This device allows bioprinting at high cell concentrations by concentrating and dispensing fibroblasts at concentrations up to 10 million cells∙mL-1. We also demonstrate that this device can be used to print bladder organoids. As the cell seeding concentration is of major importance for organogenesis in 3D culture, organoid printing allows the user to standardize the process of organoid formation and achieve more reliable and reproducible results.

MRI-Compatible and Conformal Electrocorticography Grids for Translational Research.

Intraoperative electrocorticography (ECoG) captures neural information from the surface of the cerebral cortex during surgeries such as resections for intractable epilepsy and tumors. Current clinical ECoG grids come in evenly spaced, millimeter-sized electrodes embedded in silicone rubber. Their mechanical rigidity and fixed electrode spatial resolution are common shortcomings reported by the surgical teams. Here, advances in soft neurotechnology are leveraged to manufacture conformable subdural, thin-film ECoG grids, and evaluate their suitability for translational research. Soft grids with 0.2 to 10 mm electrode pitch and diameter are embedded in 150 µm silicone membranes. The soft grids are compatible with surgical handling and can be folded to safely interface hidden cerebral surface such as the Sylvian fold in human cadaveric models. It is found that the thin-film conductor grids do not generate diagnostic-impeding imaging artefacts (<1 mm) nor adverse local heating within a standard 3T clinical magnetic resonance imaging scanner. Next, the ability of the soft grids to record subdural neural activity in minipigs acutely and two weeks postimplantation is validated. Taken together, these results suggest a promising future alternative to current stiff electrodes and may enable the future adoption of soft ECoG grids in translational research and ultimately in clinical settings.

Customizable Composite Fibers for Engineering Skeletal Muscle Models.

Engineering tissue-like scaffolds that can mimic the microstructure, architecture, topology, and mechanical properties of native tissues while offering an excellent environment for cellular growth has remained an unmet need. To address these challenges, multicompartment composite fibers are fabricated. These fibers can be assembled through textile processes to tailor tissue-level mechanical and electrical properties independent of cellular level components. Textile technologies also allow control of the distribution of different cell types and the microstructure of fabricated constructs and the direction of cellular growth within the 3D microenvironment. Here, we engineered composite fibers from biocompatible cores and biologically relevant hydrogel sheaths. The fibers are mechanically robust to being assembled using textile processes and could support adhesion, proliferation, and maturation of cell populations important for the engineering of skeletal muscles. We also demonstrated that the changes in the coating of the multicompartment fibers could potentially enhance myogenesis in vitro.

Microfluidics: A New Layer of Control for Extrusion-Based 3D Printing.

Advances in 3D printing have enabled the use of this technology in a growing number of fields, and have started to spark the interest of biologists. Having the particularity of being cell friendly and allowing multimaterial deposition, extrusion-based 3D printing has been shown to be the method of choice for bioprinting. However as biologically relevant constructs often need to be of high resolution and high complexity, new methods are needed, to provide an improved level of control on the deposited biomaterials. In this paper, we demonstrate how microfluidics can be used to add functions to extrusion 3D printers, which widens their field of application. Micromixers can be added to print heads to perform the last-second mixing of multiple components just before resin dispensing, which can be used for the deposition of new polymeric or composite materials, as well as for bioprinting new materials with tailored properties. The integration of micro-concentrators in the print heads allows a significant increase in cell concentration in bioprinting. The addition of rapid microfluidic switching as well as resolution increase through flow focusing are also demonstrated. Those elementary implementations of microfluidic functions for 3D printing pave the way for more complex applications enabling new prospects in 3D printing.

Textile Technologies and Tissue Engineering: A Path Toward Organ Weaving.

Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, microarchitecture, and mechanical properties of the fabrics play important roles in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted.

Flexible pH-Sensing Hydrogel Fibers for Epidermal Applications.

Epidermal pH is an indication of the skin's physiological condition. For example, pH of wound can be correlated to angiogenesis, protease activity, bacterial infection, etc. Chronic nonhealing wounds are known to have an elevated alkaline environment, while healing process occurs more readily in an acidic environment. Thus, dermal patches capable of continuous pH measurement can be used as point-of-care systems for monitoring skin disorder and the wound healing process. Here, pH-responsive hydrogel fibers are presented that can be used for long-term monitoring of epidermal wound condition. pH-responsive dyes are loaded into mesoporous microparticles and incorporated into hydrogel fibers using a microfluidic spinning system. The fabricated pH-responsive microfibers are flexible and can create conformal contact with skin. The response of pH-sensitive fibers with different compositions and thicknesses are characterized. The suggested technique is scalable and can be used to fabricate hydrogel-based wound dressings with clinically relevant dimensions. Images of the pH-sensing fibers during real-time pH measurement can be captured with a smart phone camera for convenient readout on-site. Through image processing, a quantitative pH map of the hydrogel fibers and the underlying tissue can be extracted. The developed skin dressing can act as a point-of-care device for monitoring the wound healing process.