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Created: 09 Sep 2015

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Volume 7, December 2016

Newsletter

3D at Purdue

3D in Focus

3D in Publications

3D in Meetings

3D at Purdue

Engineered Tissues Using Electrohydrodynamic Based 3D Printing

The tumor microenvironment is a complex, multicomponent system that drives cancer cell processes such as proliferation, senescence, and metastasis. However, the roles of individual components of the tumor microenvironment can be difficult to evaluate. Factors such as the type and conformation of extracellular matrix (ECM) proteins, the spatial patterning of cells, and the mechanical properties of the local tissue environment all contribute to driving the transition of cancer cells from a proliferative state into a more invasive (metastatic) phenotype.

The Solorio lab is currently utilizing a 3D polymer fiber writing system that allows for the fabrication of hyper-porous polymer scaffolds with patterned fiber architectures. These structures consist of only 3% solid polymer material, and can be used to support complex networks of ECM proteins. The scaffolds maintain mechanical integrity under tensile and compressive forces from cells or convective fluid flow, and can be modified to provide surface functionality as well as control over mechanical properties. The low polymer mass minimizes interference of the scaffold with interactions between the cells and ECM proteins, while enhancing the mass transport of oxygen and nutrients. Utilizing a dynamic coating technique, protein fibrillogenesis is achieved within the open area of the polymeric constructs, resulting in a 3D network of ECM fibrils that fills the free volume of the scaffold. This dynamic coating technique has been used to create scaffolds with collagen, laminin, and fibronectin networks. These modular engineered microenvironments can be seeded with a variety of cell types, enabling investigation of cell-cell or cell-matrix interactions. As such, key elements of the native cancer microenvironment can be replicated. Furthermore, we have demonstrated the successful culture of primary human metastatic breast cancer cells obtained from clinical samples of pleural effusions and ascites, providing a potential avenue for chemotherapeutic drug screening as part of precision medicine strategies.

Figure 1: Scaffolds are coated with fibronectin fibrils, filling the free volume of the scaffold (fibronectin green). Cells can then be seeded onto the scaffold and allowed to proliferate to create 3D engineered tissue (actin red, nucleus blue).

Luis Solorio

Assistant Professor

Weldon School of Biomedical Engineering

Selected publications

1. Xie F, Deng X, Kratzer D, Cheng K, Friedmann C, Qi S, Solorio L, Lahann J. Backbone-degradable polymers prepared by chemical vapor deposition, Angewandte Chemie International Edition 2017, 56: 203 –207.

2. Solorio L, Exner AA. Effect of the subcutaneous environment on phase sensitive in situ forming implant drug release, degradation, and microstructure. Journal of Pharmaceutical Sciences, 2015; 104(12): 4322-28.

3. Solorio L, Perera RH, Wu H, Gangolli M, Silverman E, Hernandez C, Peiris PM, Broome, AM, Exner AA. Nanobubble ultrasound contrast agents for enhanced delivery of thermal sensitizer to tumors undergoing radiofrequency ablation. Pharmaceutical Research, 2014; 31(6): 1407-17.

4. Patel RB^*, Solorio L^*, Wu H, Krupka T, Exner AA. Effect of injection site on in situ implant formation and drug release in vivo. Co-first author, Journal of Controlled Release, 2010 Nov 1;147(3): 350-8.

3D in Focus

Microfluidic devices and spatial confinement -

Does fluid volume matter for cell differentiation?

Microfluidics-based cultures of cells, such as hepatocytes, are being developed as platforms for toxicology and tissue engineering applications in which cells need to be properly differentiated. For convenience, like to achieve high-throughput, cell cultures might not include a complete 3D environment (e.g., multiple layers of cells in the liver), and might only recapitulate the minimal structural and functional unit of the tissue, which renders the maintenance of differentiation more difficult. The microfluidics-based devices are popular because they permit the study of a very small population of cells and the precise control of the composition and continuous perfusion flow pattern of the medium bathing the cells. It is known that the medium flow is necessary to maintain the differentiation status of cells. However, in the device, the cells are arbitrarily cultured in a small volume of medium to minimize the use of reagents and fit in the microfluidic system; yet, we do not understand the impact of fluid volume on differentiation and what would happen if the fluid circulation were not an option for certain experiments. The objective of the article highlighted in this newsletter was to investigate the spatial confinement (i.e., small volume) effect on cellular differentiation, a usually less studied aspect of the tissue microenvironment.

Featured article: Haque A, Gheibi P, Gao Y, Foster E, Son KJ, You J, Stybayeva G, Patel D, Revzin A. Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels. Sci Rep. 2016 Sep 29; 6:33980. doi: 10.1038/srep33980.

3D3C overview of the article: Primary rat hepatocytes were cultured on collagen I coated low-volume microfluidic channels; the microchamber was 1 μl in volume. Instead of continuous perfusion, the medium inside the microchambers was changed every 48 hours to allow time to witness the spatial confinement effect. The authors showed that hepatocytes cultured in the microchambers retained a differentiated hepatic phenotype for 21 days. The differentiation phenotype was illustrated by the presence of cellular polarity, high levels of E-cadherin and albumin synthesis. The levels of E-cadherin expression, albumin synthesis, and cellular polarity were impaired when the local volume in the microchambers was increased from 1 μl to 30 μl. Likewise, cells cultured in standard 12-well plates under identical conditions (same surface coating, seeding density and medium composition), but with a large amount of medium per well, were dedifferentiated after seven days. Therefore, spatial confinement in microfluidic devices, in addition to or in place of medium flow, is able to maintain the differentiation status of cells for a long period of time. The authors further showed that the differentiated phenotype was maintained at least by accumulation of hepato-inductive growth factors, such as hepatocyte growth factor, and reduction in hepato-disruptive growth factors, such as transforming growth factor (TGF)-β1, in the microchambers. According to the authors, spatial confinement, even though it has not been seen as an option, may be an important alternative in microfluidic devices to maintain the normal function of cells when continuous flow is not possible.

As it seems that spatial confinement in microchambers will help maintain the differentiation of cells, we are wondering if spatial confinement is also an important factor in vivo. We should keep in mind that the design of microfluidic devices ought to recapitulate as much as possible the conditions under which cells are in tissues. Hence, the volume of fluid or movement should mimic what exists in the tissue microenvironment. This step is currently difficult to implement because the spatial characteristics of the fluid surrounding individual cells or groups of cells in a given tissue is rarely known. The analysis of spatial confinement in real tissue is an element of the next frontier to help improve 3D cell culture devices.

3D in Publications

Complete List -- 3D culture related articles on PubMed (last 2 months)

Reviews

Scaffold free/Scaffold

Organ/Tissue/Cell

Others

3D in Publications

Complete List

Abe, T., Ohuchida, K., Koikawa, K., Endo, S., Okumura, T., Sada, M., Horioka, K., Zheng, B., Moriyama, T., Nakata, K., et al. (2016). Cancer-associated peritoneal mesothelial cells lead the formation of pancreatic cancer peritoneal dissemination. Int J Oncol.

Affolter, A., and Hess, J. (2016). [Preclinical models in head and neck tumors : Evaluation of cellular and molecular resistance mechanisms in the tumor microenvironment]. Hno 64, 860-869.

Agrawal, K., Das, V., Otmar, M., Krecmerova, M., Dzubak, P., and Hajduch, M. (2016). Cell-based DNA demethylation detection system for screening of epigenetic drugs in 2D, 3D, and xenograft models. Cytometry A.

Al Madhoun, A., Ali, H., AlKandari, S., Atizado, V. L., Akhter, N., Al-Mulla, F., and Atari, M. (2016). Defined three-dimensional culture conditions mediate efficient induction of definitive endoderm lineage from human umbilical cord Wharton's jelly mesenchymal stem cells. Stem Cell Res Ther 7, 165.

Aliabouzar, M., Zhang, L. G., and Sarkar, K. (2016). Lipid Coated Microbubbles and Low Intensity Pulsed Ultrasound Enhance Chondrogenesis of Human Mesenchymal Stem Cells in 3D Printed Scaffolds. Sci Rep 6, 37728.

Amin, J., Ramachandran, K., Williams, S. J., Lee, A., Novikova, L., and Stehno-Bittel, L. (2016). A simple, reliable method for high-throughput screening for diabetes drugs using 3D beta-cell spheroids. J Pharmacol Toxicol Methods 82, 83-89.

Atila, D., Keskin, D., and Tezcaner, A. (2016). Crosslinked pullulan/cellulose acetate fibrous scaffolds for bone tissue engineering. Mater Sci Eng C Mater Biol Appl 69, 1103-1115.

Axrap, A., Wang, J., Liu, Y., Wang, M., and Yusuf, A. (2016). Study on adhesion, proliferation and differentiation of osteoblasts promoted by new absorbable bioactive glass injection in vitro. Eur Rev Med Pharmacol Sci 20, 4677-4681.

Bach, F., Miranda-Bedate, A., van Heel, F., Riemers, F., Muller, M., Creemers, L., Ito, K., Benz, K., Meij, B., and Tryfonidou, M. (2016a). Bone morphogenetic protein-2, but not mesenchymal stromal cells, exert regenerative effects on canine and human nucleus pulposus cells. Tissue Eng Part A.

Bach, F. C., Miranda-Bedate, A., van Heel, F. W., Riemers, F. M., Muller, M. C., Creemers, L. B., Ito, K., Benz, K., Meij, B. P., and Tryfonidou, M. A. (2016b). Bone Morphogenetic Protein-2, But Not Mesenchymal Stromal Cells, Exert Regenerative Effects on Canine and Human Nucleus Pulposus Cells. Tissue Eng Part A.

Bajwa, P., Nielsen, S., Lombard, J. M., Rassam, L., Nahar, P., Rueda, B. R., Wilkinson, J. E., Miller, R. A., and Tanwar, P. S. (2016). Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice. Oncotarget.

Bartfeld, S. (2016). Modeling infectious diseases and host-microbe interactions in gastrointestinal organoids. Dev Biol 420, 262-270.

Bayar, G. R., Kuo, S., Marcelo, C. L., and Feinberg, S. E. (2016). In Vitro Development of a Mucocutaneous Junction for Lip Reconstruction. J Oral Maxillofac Surg 74, 2317-2326.

Bayat, N., Ebrahimi-Barough, S., Ardakan, M. M., Ai, A., Kamyab, A., Babaloo, N., and Ai, J. (2016a). Differentiation of Human Endometrial Stem Cells into Schwann Cells in Fibrin Hydrogel as 3D Culture. Mol Neurobiol 53, 7170-7176.

Bayat, N., Ebrahimi-Barough, S., Norouzi-Javidan, A., Saberi, H., Tajerian, R., Ardakan, M. M., Shirian, S., Ai, A., and Ai, J. (2016b). Apoptotic effect of atorvastatin in glioblastoma spheroids tumor cultured in fibrin gel. Biomed Pharmacother.

Bayer, E. A., Fedorchak, M. V., and Little, S. R. (2016). The Influence of Platelet-Derived Growth Factor and Bone Morphogenetic Protein Presentation on Tubule Organization by Human Umbilical Vascular Endothelial Cells and Human Mesenchymal Stem Cells in Coculture. Tissue Eng Part A 22, 1296-1304.

Bellotti, C., Duchi, S., Bevilacqua, A., Lucarelli, E., and Piccinini, F. (2016). Long term morphological characterization of mesenchymal stromal cells 3D spheroids built with a rapid method based on entry-level equipment. Cytotechnology 68, 2479-2490.

Bensing, C., Mojic, M., Gomez-Ruiz, S., Carralero, S., Dojcinovic, B., Maksimovic-Ivanic, D., Mijatovic, S., and Kaluderovic, G. N. (2016a). Evaluation of functionalized mesoporous silica SBA-15 as a carrier system for Ph3Sn(CH2)3OH against the A2780 ovarian carcinoma cell line. Dalton Trans 45, 18984-18993.

Bensing, C., Mojic, M., Gomez-Ruiz, S., Carralero, S., Dojcinovic, B., Maksimovic-Ivanic, D., Mijatovic, S., and Kaluderovic, G. N. (2016b). Evaluation of functionalized mesoporous silica SBA-15 as a carrier system for Ph3Sn(CH2)3OH against the A2780 ovarian carcinoma cell line. Dalton Trans 45, 18984-18993.

Bento, A. R., Quelhas, P., Oliveira, M. J., Pego, A. P., and Amaral, I. F. (2016). Three-dimensional culture of single embryonic stem-derived neural/stem progenitor cells in fibrin hydrogels: neuronal network formation and matrix remodelling. J Tissue Eng Regen Med.

Bhat, S. K., Joshi, M. B., Ullah, A., Masood, R., Biligiri, S. G., Arni, R. K., and Satyamoorthy, K. (2016). Serine proteinases from Bothrops snake venom activates PI3K/Akt mediated angiogenesis. Toxicon 124, 63-72.

Bianchi, V. J., Weber, J. F., Waldman, S. D., Backstein, D., and Kandel, R. (2016). Formation of Hyaline Cartilage Tissue by Passaged Human Osteoarthritic Chondrocytes. Tissue Eng Part A.

Bodenberger, N., Kubiczek, D., Paul, P., Preising, N., Weber, L., Bosch, R., Hausmann, R., Gottschalk, K. E., and Rosenau, F. (2016). Beyond bread and beer: whole cell protein extracts from baker's yeast as a bulk source for 3D cell culture matrices. Appl Microbiol Biotechnol.

Boehme, K. A., Nitsch, J., Riester, R., Handgretinger, R., Schleicher, S. B., Kluba, T., and Traub, F. (2016). Arsenic trioxide potentiates the effectiveness of etoposide in Ewing sarcomas. Int J Oncol 49, 2135-2146.

Bouchet, B. P., Noordstra, I., van Amersfoort, M., Katrukha, E. A., Ammon, Y. C., Ter Hoeve, N. D., Hodgson, L., Dogterom, M., Derksen, P. W., and Akhmanova, A. (2016). Mesenchymal Cell Invasion Requires Cooperative Regulation of Persistent Microtubule Growth by SLAIN2 and CLASP1. Dev Cell 39, 708-723.

Brajsa, K., Vujasinovic, I., Jelic, D., Trzun, M., Zlatar, I., Karminski-Zamola, G., and Hranjec, M. (2016). Antitumor activity of amidino-substituted benzimidazole and benzimidazo[1,2-a]quinoline derivatives tested in 2D and 3D cell culture systems. J Enzyme Inhib Med Chem 31, 1139-1145.

Burek, M., Waskiewicz, S., Lalik, A., Student, S., Bieg, T., and Wandzik, I. (2016). Thermoresponsive microgels containing trehalose as soft matrices for 3D cell culture. Biomater Sci.

Butter, A., Aliyev, K., Hillebrandt, K. H., Raschzok, N., Kluge, M., Seiffert, N., Tang, P., Napierala, H., Ashraf, M. I., Reutzel-Selke, A., et al. (2016). Evolution of graft morphology and function after recellularization of decellularized rat livers. J Tissue Eng Regen Med.

Cepeda, M. A., Pelling, J. J., Evered, C. L., Leong, H. S., and Damjanovski, S. (2016). The cytoplasmic domain of MT1-MMP is dispensable for migration augmentation but necessary to mediate viability of MCF-7 breast cancer cells. Exp Cell Res.

Chacon-Martinez, C. A., Klose, M., Niemann, C., Glauche, I., and Wickstrom, S. A. (2016). Hair follicle stem cell cultures reveal self-organizing plasticity of stem cells and their progeny. Embo j.

Chen, C. S. (2016). 3D Biomimetic Cultures: The Next Platform for Cell Biology. Trends Cell Biol 26, 798-800.

Chen, D. W., and Foldvari, M. (2016). In vitro bioassay model for screening non-viral neurotrophic factor gene delivery systems for glaucoma treatment. Drug Deliv Transl Res 6, 676-685.

Chen, G., Xu, R., Zhang, C., and Lv, Y. (2016a). Responses of MSCs to 3D Scaffold Matrix Mechanical Properties under Oscillatory Perfusion Culture. ACS Appl Mater Interfaces.

Chen, J., Yuan, Z., Liu, Y., Zheng, R., Dai, Y., Tao, R., Xia, H., Liu, H., Zhang, Z., Zhang, W., et al. (2016b). Improvement of In Vitro Three-Dimensional Cartilage Regeneration by a Novel Hydrostatic Pressure Bioreactor. Stem Cells Transl Med.

Chen, Y. Y., Silva, P. N., Syed, A. M., Sindhwani, S., Rocheleau, J. V., and Chan, W. C. (2016c). Clarifying intact 3D tissues on a microfluidic chip for high-throughput structural analysis. Proc Natl Acad Sci U S A.

Cho, H., Tarafder, S., Fogge, M., Kao, K., and Lee, C. H. (2016). Periodontal ligament stem/progenitor cells with protein-releasing scaffolds for cementum formation and integration on dentin surface. Connect Tissue Res 57, 488-495.

Choi, J., Iich, E., and Lee, J. H. (2016a). Organogenesis of adult lung in a dish: Differentiation, disease and therapy. Dev Biol 420, 278-286.

Choi, S. H., Kim, Y. H., Quinti, L., Tanzi, R. E., and Kim, D. Y. (2016b). 3D culture models of Alzheimer's disease: a road map to a "cure-in-a-dish". Mol Neurodegener 11, 75.

Clements, L. E., Garvican, E. R., Dudhia, J., and Smith, R. K. (2016). Modulation of mesenchymal stem cell genotype and phenotype by extracellular matrix proteins. Connect Tissue Res 57, 443-453.

Colacino, J. A. (2016). 3D human tissue culture: modeling environmental effects on the stem cell epigenome. Epigenomics 8, 1453-1457.

Costa, E. C., Moreira, A. F., de Melo-Diogo, D., Gaspar, V. M., Carvalho, M. P., and Correia, I. J. (2016). 3D tumor spheroids: an overview on the tools and techniques used for their analysis. Biotechnol Adv 34, 1427-1441.

Cubo, N., Garcia, M., Del Canizo, J. F., Velasco, D., and Jorcano, J. L. (2016). 3D bioprinting of functional human skin: production and in vivo analysis. Biofabrication 9, 015006.

Das, P. K., Puusepp, L., Varghese, F. S., Utt, A., Ahola, T., Kananovich, D. G., Lopp, M., Merits, A., and Karelson, M. (2016). Design and Validation of Novel Chikungunya Virus Protease Inhibitors. Antimicrob Agents Chemother 60, 7382-7395.

Dittmer, A., Woskobojnik, I., Adfeldt, R., Drach, J. C., Townsend, L. B., Voigt, S., and Bogner, E. (2016). Tetrahalogenated benzimidazole D-ribonucleosides are active against rat cytomegalovirus. Antiviral Res 137, 102-107.

do Nascimento Pedrosa, T., De Vuyst, E., Mound, A., Lambert de Rouvroit, C., Maria-Engler, S. S., and Poumay, Y. (2016). Methyl-beta-cyclodextrin treatment combined to incubation with interleukin-4 reproduces major features of atopic dermatitis in a 3D-culture model. Arch Dermatol Res.

Domejean, H., de la Motte Saint Pierre, M., Funfak, A., Atrux-Tallau, N., Alessandri, K., Nassoy, P., Bibette, J., and Bremond, N. (2016). Controlled production of sub-millimeter liquid core hydrogel capsules for parallelized 3D cell culture. Lab Chip.

Domert, J., Sackmann, C., Severinsson, E., Agholme, L., Bergstrom, J., Ingelsson, M., and Hallbeck, M. (2016). Aggregated Alpha-Synuclein Transfer Efficiently between Cultured Human Neuron-Like Cells and Localize to Lysosomes. PLoS One 11, e0168700.

Drifka, C. R., Loeffler, A. G., Esquibel, C. R., Weber, S. M., Eliceiri, K. W., and Kao, W. J. (2016). Human pancreatic stellate cells modulate 3D collagen alignment to promote the migration of pancreatic ductal adenocarcinoma cells. Biomed Microdevices 18, 105.

Erndt-Marino, J., and Hahn, M. S. (2016). Probing the response of human osteoblasts following exposure to sympathetic neuron-like PC-12 cells in a 3D co-culture model. J Biomed Mater Res A.

Eyckmans, J., and Chen, C. S. (2016). 3D culture models of tissues under tension. J Cell Sci.

Fan, R., Piou, M., Darling, E., Cormier, D., Sun, J., and Wan, J. (2016). Bio-printing cell-laden Matrigel-agarose constructs. J Biomater Appl 31, 684-692.

Fong, E. L., Harrington, D. A., Farach-Carson, M. C., and Yu, H. (2016). Heralding a new paradigm in 3D tumor modeling. Biomaterials 108, 197-213.

Forrestal, D. P., Klein, T. J., and Woodruff, M. A. (2016). Challenges in engineering large customized bone constructs. Biotechnol Bioeng.

Freeman, F. E., and McNamara, L. M. (2016). Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration. Tissue Eng Part B Rev.

Furuhata, Y., Kikuchi, Y., Tomita, S., and Yoshimoto, K. (2016). Small spheroids of adipose-derived stem cells with time-dependent enhancement of IL-8 and VEGF-A secretion. Genes Cells.

Galbraith, T., Clafshenkel, W. P., Kawecki, F., Blanckaert, C., Labbe, B., Fortin, M., Auger, F. A., and Fradette, J. (2016). A Cell-Based Self-Assembly Approach for the Production of Human Osseous Tissues from Adipose-Derived Stromal/Stem Cells. Adv Healthc Mater.

Ganesan, M. K., Finsterwalder, R., Leb, H., Resch, U., Neumuller, K., de Martin, R., and Petzelbauer, P. (2016). 3D co-culture model to analyze the crosstalk between endothelial and smooth muscle cells. Tissue Eng Part C Methods.

Gardner, J. K., and Herbst-Kralovetz, M. M. (2016). Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions. Viruses 8.

Geiger, P., Mayer, B., Wiest, I., Schulze, S., Jeschke, U., and Weissenbacher, T. (2016). Binding of galectin-1 to breast cancer cells MCF7 induces apoptosis and inhibition of proliferation in vitro in a 2D- and 3D- cell culture model. BMC Cancer 16, 870.

Ghourichaee, S. S., Powell, E. M., and Leach, J. B. (2016). Enhancement of human neural stem cell self-renewal in 3D hypoxic culture. Biotechnol Bioeng.

Gonneaud, A., Jones, C., Turgeon, N., Levesque, D., Asselin, C., Boudreau, F., and Boisvert, F. M. (2016). A SILAC-Based Method for Quantitative Proteomic Analysis of Intestinal Organoids. Sci Rep 6, 38195.

Grego, S., Dougherty, E. R., Alexander, F. J., Auerbach, S. S., Berridge, B. R., Bittner, M. L., Casey, W., Cooley, P. C., Dash, A., Ferguson, S. S., et al. (2016). Systems biology for organotypic cell cultures. Altex.

Gulati, K., Kogawa, M., Prideaux, M., Findlay, D. M., Atkins, G. J., and Losic, D. (2016a). Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability. Mater Sci Eng C Mater Biol Appl 69, 831-840.

Gulati, K., Prideaux, M., Kogawa, M., Lima-Marques, L., Atkins, G. J., Findlay, D. M., and Losic, D. (2016b). Anodized 3D-printed titanium implants with dual micro- and nano-scale topography promote interaction with human osteoblasts and osteocyte-like cells. J Tissue Eng Regen Med.

Guneta, V., Tan, N. S., Chan, S. K., Tanavde, V., Lim, T. C., Wong, T. C., and Choong, C. (2016). Comparative study of adipose-derived stem cells and bone marrow-derived stem cells in similar microenvironmental conditions. Exp Cell Res 348, 155-164.

Gurumurthy, B., Bierdeman, P. C., and Janorkar, A. V. (2016). Spheroid model for functional osteogenic evaluation of human adipose derived stem cells. J Biomed Mater Res A.

Gwon, K., Kim, E., and Tae, G. (2016). Heparin-hyaluronic acid hydrogel for efficient cellular activities of 3D encapsulated adipose derived stem cells. Acta Biomater.

Hamlet, S. M., Vaquette, C., Shah, A., Hutmacher, D. W., and Ivanovski, S. (2016). 3-Dimensional functionalized polycaprolactone-hyaluronic acid hydrogel constructs for bone tissue engineering. J Clin Periodontol.

Hernandez Vera, R., Schwan, E., Fatsis-Kavalopoulos, N., and Kreuger, J. (2016). A Modular and Affordable Time-Lapse Imaging and Incubation System Based on 3D-Printed Parts, a Smartphone, and Off-The-Shelf Electronics. PLoS One 11, e0167583.

Hindley, C. J., Cordero-Espinoza, L., and Huch, M. (2016). Organoids from adult liver and pancreas: Stem cell biology and biomedical utility. Dev Biol 420, 251-261.

Horvath, P., Aulner, N., Bickle, M., Davies, A. M., Nery, E. D., Ebner, D., Montoya, M. C., Ostling, P., Pietiainen, V., Price, L. S., et al. (2016). Screening out irrelevant cell-based models of disease. Nat Rev Drug Discov 15, 751-769.

Houshmand, M., Soleimani, M., Atashi, A., Saglio, G., Abdollahi, M., and Nikougoftar Zarif, M. (2016). Mimicking the Acute myeloid leukemia niche for molecular study and drug screening. Tissue Eng Part C Methods.

Hudson, K. D., and Bonassar, L. J. (2016). Hypoxic Expansion of Human Mesenchymal Stem Cells Enhances 3D Maturation of Tissue Engineered Intervertebral Discs. Tissue Eng Part A.

Hunt, N. C., Hallam, D., Karimi, A., Mellough, C. B., Chen, J., Steel, D. H., and Lako, M. (2016). 3D culture of human pluripotent stem cells in RGD-alginate hydrogel improves retinal tissue development. Acta Biomater.

Hynes, J., Carey, C., and Will, Y. (2016). Fluorescence-Based Microplate Assays for In Vitro Assessment of Mitochondrial Toxicity, Metabolic Perturbation, and Cellular Oxygenation. Curr Protoc Toxicol 70, 2.16.11-12.16.30.

Ingthorsson, S., Briem, E., Bergthorsson, J. T., and Gudjonsson, T. (2016). Epithelial Plasticity During Human Breast Morphogenesis and Cancer Progression. J Mammary Gland Biol Neoplasia.

Jamieson, P. R., Dekkers, J. F., Rios, A. C., Fu, N. Y., Lindeman, G. J., and Visvader, J. E. (2016). Derivation of a robust mouse mammary organoid system for studying tissue dynamics. Development.

Jenkins, J., Borisov, S. M., Papkovsky, D. B., and Dmitriev, R. I. (2016). Sulforhodamine Nanothermometer for Multiparametric Fluorescence Lifetime Imaging Microscopy. Anal Chem 88, 10566-10572.

Jeong, Y. G., Lee, J. S., Shim, J. K., and Hur, W. (2016). A scaffold-free surface culture of B16F10 murine melanoma cells based on magnetic levitation. Cytotechnology 68, 2323-2334.

Joo, S., Oh, S. H., Sittadjody, S., Opara, E. C., Jackson, J. D., Lee, S. J., Yoo, J. J., and Atala, A. (2016). The effect of collagen hydrogel on 3D culture of ovarian follicles. Biomed Mater 11, 065009.

Jorgenson, A. J., Choi, K. M., Sicard, D., Smith, K. M., Hiemer, S. E., Varelas, X., and Tschumperlin, D. J. (2016). TAZ activation drives fibroblast spheroid growth, expression of pro-fibrotic paracrine signals, and context dependent ECM gene expression. Am J Physiol Cell Physiol, ajpcell.00205.02016.

Kaisar, M. A., Sajja, R. K., Prasad, S., Abhyankar, V. V., Liles, T., and Cucullo, L. (2016). New experimental models of the blood-brain barrier for CNS drug discovery. Expert Opin Drug Discov, 1-15.

Kamei, K. I., Koyama, Y., Tokunaga, Y., Mashimo, Y., Yoshioka, M., Fockenberg, C., Mosbergen, R., Korn, O., Wells, C., and Chen, Y. (2016). Characterization of Phenotypic and Transcriptional Differences in Human Pluripotent Stem Cells under 2D and 3D Culture Conditions. Adv Healthc Mater 5, 2951-2958.

Khalil, S., El-Badri, N., El-Mokhtaar, M., Al-Mofty, S., Farghaly, M., Ayman, R., Habib, D., and Mousa, N. (2016). A Cost-Effective Method to Assemble Biomimetic 3D Cell Culture Platforms. PLoS One 11, e0167116.

Kim, S. K., Lee, J., Song, M., Kim, M., Hwang, S. J., Jang, H., and Park, Y. (2016a). Combination of three angiogenic growth factors has synergistic effects on sprouting of endothelial cell/mesenchymal stem cell-based spheroids in a 3D matrix. J Biomed Mater Res B Appl Biomater 104, 1535-1543.

Kim, Y. Y., Tamadon, A., and Ku, S. Y. (2016b). Potential Use of Antiapoptotic Proteins and Noncoding RNAs for Efficient In Vitro Follicular Maturation and Ovarian Bioengineering. Tissue Eng Part B Rev.

Kinoshita, K., Iwase, M., Yamada, M., Yajima, Y., and Seki, M. (2016). Fabrication of multilayered vascular tissues using microfluidic agarose hydrogel platforms. Biotechnol J 11, 1415-1423.

Kumar, D., Lyness, A., Gerges, I., Lenardi, C., Forsyth, N. R., and Liu, Y. (2016a). Stem Cell Delivery With Polymer Hydrogel for Treatment of Intervertebral Disc Degeneration: From 3D Culture to Design of the Delivery Device for Minimally Invasive Therapy. Cell Transplant 25, 2213-2220.

Kumar, M., Coburn, J., Kaplan, D. L., and Mandal, B. B. (2016b). Immuno-Informed 3D Silk Biomaterials for Tailoring Biological Responses. ACS Appl Mater Interfaces 8, 29310-29322.

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