Abstract As bioprinting advances into clinical relevance with patient-specific tissue and organ constructs, it must be capable of multi-material fabrication at high resolutions to accurately mimick the complex tissue structures found in the body. One of the most fundamental structures to regenerative medicine is microvasculature. Its continuous hierarchical branching vessel networks bridge surgically manipulatable arteries (∼1–6 mm) to capillary beds (∼10µm). Microvascular perfusion must be established quickly for autologous, allogeneic, or tissue engineered grafts to survive implantation and heal in place. However, traditional syringe-based bioprinting techniques have struggled to produce perfusable constructs with hierarchical branching at the resolution of the arterioles (∼100-10µm) found in microvascular tissues. This study introduces the novel CEVIC bioprinting device (i.e.ContinuouslyExtrudedVariableInternalChanneling), a multi-material technology that breaks the current extrusion-based bioprinting paradigm of pushing cell-laden hydrogels through a nozzle as filaments, instead, in the version explored here, extruding thin, wide cell-laden hydrogel sheets. The CEVIC device adapts the chaotic printing approach to control the width and number of microchannels within the construct as it is extruded (i.e. on-the-fly). Utilizing novel flow valve designs, this strategy can produce continuous gradients varying geometry and materials across the construct and hierarchical branching channels with average widths ranging from 621.5 ± 42.92%µm to 11.67 ± 14.99%µm, respectively, encompassing the resolution range of microvascular vessels. These constructs can also include fugitive/sacrificial ink that vacates to leave demonstrably perfusable channels. In a proof-of-concept experiment, a co-culture of two microvascular cell types, endothelial cells and pericytes, sustained over 90% viability throughout 1 week in microchannels within CEVIC-produced gelatin methacryloyl-sodium alginate hydrogel constructs. These results justify further exploration of generating CEVIC-bioprinted microvasculature, such as pre-culturing and implantation studies.
more »
« less
Electrothermal soft manipulator enabling safe transport and handling of thin cell/tissue sheets and bioelectronic devices
“Living” cell sheets or bioelectronic chips have great potentials to improve the quality of diagnostics and therapies. However, handling these thin and delicate materials remains a grand challenge because the external force applied for gripping and releasing can easily deform or damage the materials. This study presents a soft manipulator that can manipulate and transport cell/tissue sheets and ultrathin wearable biosensing devices seamlessly by recapitulating how a cephalopod’s suction cup works. The soft manipulator consists of an ultrafast thermo-responsive, microchanneled hydrogel layer with tissue-like softness and an electric heater layer. The electric current to the manipulator drives microchannels of the gel to shrink/expand and results in a pressure change through the microchannels. The manipulator can lift/detach an object within 10 s and can be used repeatedly over 50 times. This soft manipulator would be highly useful for safe and reliable assembly and implantation of therapeutic cell/tissue sheets and biosensing devices.
more »
« less
- PAR ID:
- 10282404
- Author(s) / Creator(s):
- ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »
- Date Published:
- Journal Name:
- Science Advances
- Volume:
- 6
- Issue:
- 42
- ISSN:
- 2375-2548
- Page Range / eLocation ID:
- eabc5630
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract A new approach is described for fabricating 3D poly(ε‐caprolactone) (PCL)/gelatin (1:1) nanofiber aerogels with patterned macrochannels and anisotropic microchannels by freeze‐casting with 3D‐printed sacrificial templates. Single layer or multiple layers of macrochannels are formed through an inverse replica of 3D‐printed templates. Aligned microchannels formed by partially anisotropic freezing act as interconnected pores between templated macrochannels. The resulting macro‐/microchannels within nanofiber aerogels significantly increase preosteoblast infiltration in vitro. The conjugation of vascular endothelial growth factor (VEGF)‐mimicking QK peptide to PCL/gelatin/gelatin methacryloyl (1:0.5:0.5) nanofiber aerogels with patterned macrochannels promotes the formation of a microvascular network of seeded human microvascular endothelial cells. Moreover, nanofiber aerogels with patterned macrochannels and anisotropic microchannels show significantly enhanced cellular infiltration rates and host tissue integration compared to aerogels without macrochannels following subcutaneous implantation in rats. Taken together, this novel class of nanofiber aerogels holds great potential in biomedical applications including tissue repair and regeneration, wound healing, and 3D tissue/disease modeling.more » « less
-
Natural muscles show tensile actuation and realize torsional rotation by combining with the skeleton, which integrate with sensing and signaling function in a single element to form a feedback loop. The currently developed artificial muscle and sensing devices always work upon external stimuli, and a separate controlling and signal transmission system is needed, increasing the complexity of muscle design. Therefore it is highly desired to develop flexible and compact fiber artificial muscles with large strain for advanced soft robotic systems. In this paper, twisted elastomer fiber artificial muscles with tensile and torsional actuations and sensing function by a single electric signal are developed, by using twisted natural rubber fiber coated with a buckled carbon nanotube sheet. The twisted natural rubber fiber can be electrothermally actuated to show contraction and rotation by entropic elasticity. The buckled carbon nanotube sheet can transmit electric current, and the contact area between the buckled carbon nanotube sheets increased during actuation, resulting in resistance decrease by thermo-piezoresistive effect. A feedback circuit was designed to connect or disconnect the electric current by measuring the resistance change to form a feedback loop to control on/off of the muscle. The current study provides a new muscle design for soft robotics, controllers, and human-machine integration.more » « less
-
Electrically responsive biomaterials are an important and emerging technology in the fields of biomedical and material sciences. A great deal of research explores the integral role of electrical conduction in normal and diseased cell biology, and material scientists are focusing an even greater amount of attention on natural and hybrid materials as sources of biomaterials which can mimic the properties of cells. This review establishes a summary of those efforts for the latter group, detailing the current materials, theories, methods, and applications of electrically conductive biomaterials fabricated from protein polymers and polysaccharides. These materials can be used to improve human life through novel drug delivery, tissue regeneration, and biosensing technologies. The immediate goal of this review is to establish fabrication methods for protein and polysaccharide-based materials that are biocompatible and feature modular electrical properties. Ideally, these materials will be inexpensive to make with salable production strategies, in addition to being both renewable and biocompatible.more » « less
-
Abstract Neural interface technologies are increasingly evolving towards bio-inspired approaches to enhance integration and long-term functionality. Recent strategies merge soft materials with tissue engineering to realize biologically-active and/or cell-containing living layers at the tissue-device interface that enable seamless biointegration and novel cell-mediated therapeutic opportunities. This review maps the field of bio-inspired electronics and discusses key recent developments in tissue-like and regenerative bioelectronics, from soft biomaterials and surface-functionalized bioactive coatings to cell-containing ‘biohybrid’ and ‘all-living’ interfaces. We define and contextualize key terminology in this emerging field and highlight how biological and living components can bridge the gap to clinical translation.more » « less
An official website of the United States government

