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Biology subjects

Rosalia, L.

Publications and source records attributed to Rosalia, L..

5 recordsLinked to original sources

Gradient Multinozzle 3D Printing

Direct ink writing is compatible with an expansive materials palette. While enabling diverse applications, this materials versatility brings significant bottlenecks in ink formulation, often requiring the mixing, printing, and testing of dozens to hundreds of ink compositions over the course of a project. To accelerate ink-space exploration, we introduce gradient embedded multinozzle (GEM) printheads that combine the high-throughput parallelized printing of multinozzles with combinatorial ink mixing. These printheads allow simultaneous mixing of two-, three-, and four-input inks which are distributed to printer nozzles to create complex 3D structures with graded compositions of inks. Using a two-way GEM printhead, we vali-date cell compatibility by printing scaffolds containing various concentrations of fibroblasts and observing non-linear compaction behaviours. We next test a three-way GEM multinozzle to print ten compositions of di- and multi-functionalized poly(ethylene-glycol) diacrylate hydrogel tri-leaflet valves, optimizing for stiffness, swelling ratio, and toughness. Our GEM multinozzles are compatible with open-source printers and either pressure- or volume-driven extrusion systems and promise to accelerate iterative ink design and testing.

bioengineering↗

Programmable 3D cell alignment of bioprinted tissue via soft robotic dynamic stimulation

Recent breakthroughs in biofabrication have enabled the development of engineered tissues for various organ systems, supporting applications in drug testing and regenerative medicine. However, current approaches do not allow for dynamic mechanical maturation of engineered tissue in 3D. Although uniaxial mechanostimulation techniques have shown promise in generating anisotropic tissues, they fail to recapitulate the biomechanics of complex tissues. As a result, existing biofabricated tissues lack the ability to replicate complex 3D alignment patterns essential for functional biomimicry. Here, we present a soft robotics-driven approach for programmable 3D alignment in 3D bioprinted tissue. Our method introduces the co-printing of biological tissue with a silicone-based soft robot via a custom core-double shell nozzle. The application of 3D, exogenous, dynamic expansion and torsional forces to the tissue via the co-printed silicone robot was found to drive cell alignment. Confocal imaging revealed pronounced anisotropy of the stimulated tissue samples compared to the unstimulated controls. In addition, different cellular orientation patterns resulted from each mode of stimulation, demonstrating the versatility of the soft robotic approach in tailoring the pattern of tissue alignment based on programmed mechanostimulation.

bioengineering↗

A low-cost, open-source 3D printer for multimaterial and high-throughput direct ink writing of soft and living materials

Direct ink writing is a 3D printing method that is compatible with a wide range of structural, elastomeric, electronic, and living materials, and it continues to expand its uses into physics, engineering, and biology laboratories. However, the large footprint, closed hardware and software ecosystems, and expense of commercial systems often hamper widespread adoption. Here, we present a compact, simple-to-build, low-cost, multimaterial, and high-throughput direct ink writing 3D printer platform with detailed assembly files and instructions provided freely online. In contrast to existing low-cost 3D printers and bioprinters, which typically modify off-the-shelf plastic 3D printers, this system is built from scratch, offering a lower cost and full customizability. Despite its low cost, we demonstrate advanced active mixing and multimaterial multinozzle 3D (MM3D) printing methods, which previously have relied on expensive and custom motion control platforms. We finally introduce embedded multinozzle and 3D gradient nozzle designs that offer high throughput and graded 3D parts. This powerful, easy-to-build, and customizable printing platform can help stimulate a vibrant biomaker community of engineers, biologists, and educators.

bioengineering↗

Soft robotics-enabled large animal model of HFpEF hemodynamics for device testing

Heart failure with preserved ejection fraction (HFpEF) is a major challenge in cardiovascular medicine, accounting for approximately 50% of all cases of heart failure. Due to the lack of effective therapies for this condition, the mortality associated with HFpEF remains higher than that of most cancers. Despite the ongoing efforts, no medical device has yet received FDA approval. This is largely due to the lack of an in vivo model of the HFpEF hemodynamics, resulting in the inability to evaluate device effectiveness in vivo prior to clinical trials. Here, we describe the development of a highly tunable porcine model of HFpEF hemodynamics using implantable soft robotic sleeves, where controlled actuation of a left ventricular and an aortic sleeve can recapitulate changes in ventricular compliance and afterload associated with a broad spectrum of HFpEF hemodynamic phenotypes. We demonstrate the feasibility of the proposed model in preclinical testing by evaluating the hemodynamic response of the model post-implantation of an interatrial shunt device, which was found to be consistent with findings from in silico studies and clinical trials. This work addresses several of the limitations associated with previous models of HFpEF, such as their limited hemodynamic fidelity, elevated costs, lengthy development time, and low throughput. By showcasing exceptional versatility and tunability, the proposed platform has the potential to revolutionize the current approach for HFpEF device development and selection, with the goal of improving the quality of life for the 32 million people affected by HFpEF worldwide.

bioengineering↗

A magnetically actuated, optically sensed tensile testing method for mechanical characterisation of soft biological tissues

Mechanical properties of soft biological tissues play a key role in their normal physiology, contributing to their formation during development, maintenance and repair during adult homeostasis, and driving diseases such as cancer. Mechanics has been proposed to exert its effect by impacting cells fate decisions and cell behaviours including proliferation, differentiation and motility, amongst others. However, despite its critical relevance, a comprehensive analysis of the biomechanics of soft biological tissues is still lacking due to the limitations of the existing characterisation tools. In this article, we describe the development of a device for uniaxial tensile testing of small samples of epithelial and connective tissues, based on the closed-loop interaction between an electromagnetic force actuator and an optical strain sensor. First, we validate the device with synthetic elastomers of known mechanical properties and compare its performance with conventional tensile testing methods; then, we characterise the mechanical properties of the squamous epithelium of the mouse oesophagus along with its supporting connective tissue and underlying muscle in controlled environmental conditions. Through an analysis of strain-stress curves, we demonstrate that the whole oesophagus behaves as a trilayered composite material, whose overall mechanical response depends on the properties of each of its tissue layers. Overall, the proposed setup enables measurements of the mechanical properties of soft biological tissues with unprecedented reliability and precision, and offers an ideal platform for future instrument developments.

biophysics↗