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Browsing by Subject "3D bioprinting"
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Item 3D Printing of Human Ossicle Models for the Biofabrication of Personalized Middle Ear Prostheses(MDPI, 2022-10-31) Dairaghi, Jacob; Rogozea, Dan; Cadle, Rachel; Bustamante, Joseph; Moldovan, Leni; Petrache, Horia I.; Moldovan, Nicanor I.; Physics, School of ScienceThe middle ear bones (‘ossicles’) may become severely damaged due to accidents or to diseases. In these situations, the most common current treatments include replacing them with cadaver-derived ossicles, using a metal (usually titanium) prosthesis, or introducing bridges made of biocompatible ceramics. Neither of these solutions is ideal, due to the difficulty in finding or producing shape-matching replacements. However, the advent of additive manufacturing applications to biomedical problems has created the possibility of 3D-printing anatomically correct, shape- and size-personalized ossicle prostheses. To demonstrate this concept, we generated and printed several models of ossicles, as solid, porous, or soft material structures. These models were first printed with a plottable calcium phosphate/hydroxyapatite paste by extrusion on a solid support or embedded in a Carbopol hydrogel bath, followed by temperature-induced hardening. We then also printed an ossicle model with this ceramic in a porous format, followed by loading and crosslinking an alginate hydrogel within the pores, which was validated by microCT imaging. Finally, ossicle models were printed using alginate as well as a cell-containing nanocellulose-based bioink, within the supporting hydrogel bath. In selected cases, the devised workflow and the printouts were tested for repeatability. In conclusion, we demonstrate that moving beyond simplistic geometric bridges to anatomically realistic constructs is possible by 3D printing with various biocompatible materials and hydrogels, thus opening the way towards the in vitro generation of personalized middle ear prostheses for implantation.Item Design and Implementation of Anatomically Inspired Mesenteric and Intestinal Vascular Patterns for Personalized 3D Bioprinting(MDPI, 2022-04-27) Cadle, Rachel; Rogozea, Dan; Moldovan, Leni; Moldovan, Nicanor I.; Surgery, School of MedicineRecent progress in bioprinting has made possible the creation of complex 3D intestinal constructs, including vascularized villi. However, for their integration into functional units useful for experimentation or implantation, the next challenge is to endow them with a larger-scale, anatomically realistic vasculature. In general, the perfusion of bioprinted constructs has remained difficult, and the current solution is to provide them with mostly linear and simply branched channels. To address this limitation, here we demonstrated an image analysis-based workflow leading through computer-assisted design from anatomic images of rodent mesentery and colon to the actual printing of such patterns with paste and hydrogel bioinks. Moreover, we reverse-engineered the 2D intestinal image-derived designs into cylindrical objects, and 3D-printed them in a support hydrogel. These results open the path towards generation of more realistically vascularized tissue constructs for a variety of personalized medicine applications.Item Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting(Liebert, 2017-06) Moldovan, Nicanor I.; Hibino, Narutoshi; Nakayama, Koichi; Biomedical Engineering, School of Engineering and TechnologyBioprinting is a technology with the prospect to change the way many diseases are treated, by replacing the damaged tissues with live de novo created biosimilar constructs. However, after more than a decade of incubation and many proofs of concept, the field is still in its infancy. The current stagnation is the consequence of its early success: the first bioprinters, and most of those that followed, were modified versions of the three-dimensional printers used in additive manufacturing, redesigned for layer-by-layer dispersion of biomaterials. In all variants (inkjet, microextrusion, or laser assisted), this approach is material (“scaffold”) dependent and energy intensive, making it hardly compatible with some of the intended biological applications. Instead, the future of bioprinting may benefit from the use of gentler scaffold-free bioassembling methods. A substantial body of evidence has accumulated, indicating this is possible by use of preformed cell spheroids, which have been assembled in cartilage, bone, and cardiac muscle-like constructs. However, a commercial instrument capable to directly and precisely “print” spheroids has not been available until the invention of the microneedles-based (“Kenzan”) spheroid assembling and the launching in Japan of a bioprinter based on this method. This robotic platform laces spheroids into predesigned contiguous structures with micron-level precision, using stainless steel microneedles (“kenzans”) as temporary support. These constructs are further cultivated until the spheroids fuse into cellular aggregates and synthesize their own extracellular matrix, thus attaining the needed structural organization and robustness. This novel technology opens wide opportunities for bioengineering of tissues and organs.Item Study on the technology and properties of 3D bioprinting SF/GT/n-HA composite scaffolds(Elsevier, 2019-03) Wu, Xiaofang; Chen, Kai; Zhang, Dekun; Xu, Linmin; Yang, Xuehui; Mechanical and Energy Engineering, School of Engineering and TechnologyIn this paper, three kinds of natural polymer materials, silk fibroin (SF), gelatin (GT), and nano-hydroxyapatite (n-HA), are mixed as 3D printing bioink to mimic protein polysaccharide and collagen fibers in natural articular cartilage. By changing the SF content, SF/GT/n-HA composite scaffolds with different ratios are prepared using 3D bioprinting technology. The microstructure and morphology, biological properties and mechanical properties of composite scaffolds are characterized. The results show that the printing precision of the bioink with 10% SF is best, and the composite scaffold with 10% SF also exhibits better mechanical properties, whose tensile elastic modulus is 10.60 ± 0.32 MPa and the compression elastic modulus is 1.22 ± 0.06 MPa. These studies are helpful to understand the interaction between SF, GT and n-HA, and provide a theoretical basis for the preparation of better silk fibroin-based composite scaffolds.Item Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis(Karger, 2021) Lagatuz, Mark; Vyas, Ruchi J.; Predovic, Marina; Lim, Shiyin; Jacobs, Nicole; Martinho, Miguel; Valizadegan, Hamed; Kao, David; Oza, Nikunj; Theriot, Corey A.; Zanello, Susana B.; Taibbi, Giovanni; Vizzeri, Gianmarco; Dupont, Mariana; Grant, Maria B.; Lindner, Daniel J.; Reinecker, Hans-Christian; Pinhas, Alexander; Chui, Toco Y.; Rosen, Richard B.; Moldovan, Nicanor; Vickerman, Mary B.; Radhakrishnan, Krishnan; Parsons-Wingerter, Patricia; Ophthalmology, School of MedicineThe molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA’s globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique “fingerprint” or “biomarker” vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.