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- ItemMelt Electrowriting of Graded Porous Scaffolds to Mimic the Matrix Structure of the Human Trabecular Meshwork(Washington, DC : ACS Publ., 2022) Włodarczyk-Biegun, Małgorzata K.; Villiou, Maria; Koch, Marcus; Muth, Christina; Wang, Peixi; Ott, Jenna; del Campo, AranzazuThe permeability of the human trabecular meshwork (HTM) regulates eye pressure via a porosity gradient across its thickness modulated by stacked layers of matrix fibrils and cells. Changes in HTM porosity are associated with increases in intraocular pressure and the progress of diseases such as glaucoma. Engineered HTMs could help to understand the structure-function relation in natural tissues and lead to new regenerative solutions. Here, melt electrowriting (MEW) is explored as a biofabrication technique to produce fibrillar, porous scaffolds that mimic the multilayer, gradient structure of native HTM. Poly(caprolactone) constructs with a height of 125-500 μm and fiber diameters of 10-12 μm are printed. Scaffolds with a tensile modulus between 5.6 and 13 MPa and a static compression modulus in the range of 6-360 kPa are obtained by varying the scaffold design, that is, the density and orientation of the fibers and number of stacked layers. Primary HTM cells attach to the scaffolds, proliferate, and form a confluent layer within 8-14 days, depending on the scaffold design. High cell viability and cell morphology close to that in the native tissue are observed. The present work demonstrates the utility of MEW for reconstructing complex morphological features of natural tissues.
- ItemFlexible Materials for High-Resolution 3D Printing of Microfluidic Devices with Integrated Droplet Size Regulation(Washington, DC : ACS Publications, 2021) Weigel, Niclas; Männel, Max J.; Thiele, JulianWe develop resins for high-resolution additive manufacturing of flexible micromaterials via projection microstereolithography (PμSL) screening formulations made from monomer 2-phenoxyethyl acrylate, the cross-linkers Ebecryl 8413, tri(propyleneglycol) diacrylate or 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione, the photoabsorber Sudan 1, and the photoinitiator diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide. PμSL-printed polymer micromaterials made from this resin library are characterized regarding achievable layer thickness depending on UV exposure energy, and for mechanical as well as optical properties. The best-candidate resin from this screening approach allows for 3D-printing transparent microchannels with a minimum cross section of approximately 35 × 46 μm2, which exhibit proper solvent resistance against water, isopropanol, ethanol, n-hexane, and HFE-7500. The mechanical properties are predestined for 3D-printing microfluidic devices with integrated functional units that require high material flexibility. Exemplarily, we design flexible microchannels for on-demand regulation of microdroplet sizes in microemulsion formation. Our two outlines of integrated droplet regulators operate by injecting defined volumes of air, which deform the droplet-forming microchannel cross-junction, and change the droplet size therein. With this study, we expand the library of functional resins for PμSL printing toward flexible materials with micrometer resolution and provide the basis for further exploration of these materials, e.g., as microstructured cell-culturing substrates with defined mechanics. © 2021 American Chemical Society. All rights reserved.
- ItemFabrication of Microfluidic Devices for Emulsion Formation by Microstereolithography(Basel : MDPI, 2021) Männel, Max J.; Baysak, Elif; Thiele, JulianDroplet microfluidics—the art and science of forming droplets—has been revolutionary for high-throughput screening, directed evolution, single-cell sequencing, and material design. However, traditional fabrication techniques for microfluidic devices suffer from several disadvantages, including multistep processing, expensive facilities, and limited three-dimensional (3D) design flexibility. High-resolution additive manufacturing—and in particular, projection micro-stereolithography (PµSL)—provides a promising path for overcoming these drawbacks. Similar to polydimethylsiloxane-based microfluidics 20 years ago, 3D printing methods, such as PµSL, have provided a path toward a new era of microfluidic device design. PµSL greatly simplifies the device fabrication process, especially the access to truly 3D geometries, is cost-effective, and it enables multimaterial processing. In this review, we discuss both the basics and recent innovations in PµSL; the material basis with emphasis on custom-made photopolymer formulations; multimaterial 3D printing; and, 3D-printed microfluidic devices for emulsion formation as our focus application. Our goal is to support researchers in setting up their own PµSL system to fabricate tailor-made microfluidics.
- ItemEmerging Biofabrication Techniques : A Review on Natural Polymers for Biomedical Applications(Basel : MDPI, 2021) Puertas-Bartolomé, María; Mora-Boza, Ana; García-Fernández, LuisNatural polymers have been widely used for biomedical applications in recent decades. They offer the advantages of resembling the extracellular matrix of native tissues and retaining biochemical cues and properties necessary to enhance their biocompatibility, so they usually improve the cellular attachment and behavior and avoid immunological reactions. Moreover, they offer a rapid degradability through natural enzymatic or chemical processes. However, natural polymers present poor mechanical strength, which frequently makes the manipulation processes difficult. Recent advances in biofabrication, 3D printing, microfluidics, and cell-electrospinning allow the manufacturing of complex natural polymer matrixes with biophysical and structural properties similar to those of the extracellular matrix. In addition, these techniques offer the possibility of incorporating different cell lines into the fabrication process, a revolutionary strategy broadly explored in recent years to produce cell-laden scaffolds that can better mimic the properties of functional tissues. In this review, the use of 3D printing, microfluidics, and electrospinning approaches has been extensively investigated for the biofabrication of naturally derived polymer scaffolds with encapsulated cells intended for biomedical applications (e.g., cell therapies, bone and dental grafts, cardiovascular or musculoskeletal tissue regeneration, and wound healing).