From Academia: 3D Bioprined Dendritic Vascular Networks, Cornea, Alternative Drug Delivery

Category: Blog,From Academia
blank blank Jul 16, 2020

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Generation of model tissues with dendritic vascular networks via sacrificial laser-sintered carbohydrate templates 

– Authored by Ian S. Kinstlinger, Sarah H. Saxton, Gisele A. Calderon, Karen Vasquez Ruiz, David R. Yalacki, Palvasha R. Deme, Jessica E. Rosenkrantz, Jesse D. Louis-Rosenberg, Fredrik Johansson, Kevin D. Janson, Daniel W. Sazer, Saarang S. Panchavati, Karl-Dimiter Bissig, Kelly R. Stevens & Jordan S. Miller. Nature Biomedical Engineering, 29 June 2020

Fabrication, perfusion and volumetric analysis of 3D dendritic vascular networks. a,b A dendritic vascular network computationally grown within an ellipsoidal domain was fabricated using carbohydrate SLS.c,d Sacrificially templating the dendritic carbohydrate template in a yielded the corresponding channel architecture in an agarose gel. e  Metabolic activity in a cell-laden gel was supported by perfusion (in the positive z direction) through the dendritic network, with an annular zone of cell metabolism and cell proliferation around the majority of the channels (scale bar, 5 mm). Volumetric reconstruction of MTT signal demonstrates that the metabolically active zone of cells closely follows the contour of the dendritic vascular network. g,h, Evaluating the perfusion efficacy of individual channels in a centre slice of the dendritic network shows that most channels support a robust metabolically active zone of surrounding cells and that the less effective channels collectively lie downstream of a common parent channel. Copyright.  Nature Biomedical Engineering 


Sacrificial templates for patterning perfusable vascular networks in engineered tissues have been constrained in architectural complexity, owing to the limitations of extrusion-based 3D printing techniques. Here, we show that cell-laden hydrogels can be patterned with algorithmically generated dendritic vessel networks and other complex hierarchical networks by using sacrificial templates made from laser-sintered carbohydrate powders. We quantified and modulated gradients of cell proliferation and cell metabolism emerging in response to fluid convection through these networks and to the diffusion of oxygen and metabolites out of them. We also show scalable strategies for the fabrication, perfusion culture, and volumetric analysis of large tissue-like constructs with complex and heterogeneous internal vascular architectures. Perfusable dendritic networks in cell-laden hydrogels may help sustain thick and densely cellularized engineered tissues and assist interrogations of the interplay between mass transport and tissue function.

3D printed artificial cornea for corneal stromal transplantation 

– Authored by Songul Ulag, Elif Ilhan, Ali Sahin, Betul Karademir Yilmaz, Deepak M. kalaskar, Nazmi Ekren, Osman Kilic, Faik Nuzhet Oktar, Oguzhan Gunduz. European Polymer Journal, 15 June 2020

The printing steps for production of corneal construct, solid model (a), Aluminium mold (b), 3D device (c), after printing process (d), printed corneal stroma. Copyright. European Polymer Journal


The aim of this study is to understand the optical, biocompatible, and mechanical properties of chitosan (CS) and polyvinyl-alcohol (PVA) based corneal stroma constructs using 3D printing process. The corneal stroma is tested for biocompatibility with human adipose tissue-derived mesenchymal stem cells (hASCs). Physico-chemical and chemical characterization of the construct was performed using scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR). Optical transmittance was analyzed using UV-Spectrophotometer. Results showed fabricated constructs have required shape and size. SEM images showed construct has a thickness of 400 µm. The FTIR spectra demonstrated the presence of various predicted peaks. The swelling and degradation studies of 13%(wt)PVA and 13%(wt)PVA/(1, 3, 5)%(wt)CS showed to have high swelling ratios of 7 days and degradation times of 30 days, respectively. The light transmittance values of the fabricated cornea constructs decreased with CS addition slightly. Tensile strength values decreased with increasing CS ratio, but we found to support intraocular pressure (IOP) which ranges from 12 to 22 mm-Hg. Preliminary biostability studies showed that composite constructs were compatible with hASCs even after 30 days of degradation, showing potential for these cells to be differentiated to the stroma layer in the future. This study has implications for the rapid and custom fabrication of various cornea constructs for clinical applications.

Design and Fabrication of Three-Dimensional Printed Scaffolds for Cancer Precision Medicine

Authored by Abbas Shafiee. Tissue Engineering Part A, 17 March 2020. 

Current applications of 3DP in medicine. Small circles represent manufacturing methods or devices. BJ, binder jetting; DIW, direct ink writing; DLM, direct metal laser sintering; DLP, digital light processing; FDM, fused deposition modeling; MJM, multijet modeling; SLA, stereolithography; SLM, selective laser melting; SLS, selective laser sintering. Copyright. Tissue Engineering Part A 


Three-dimensional (3D)-engineered scaffolds have been widely investigated as drug delivery systems (DDS) or cancer models with the aim to develop effective cancer therapies. The in vitro and in vivo models developed via 3D printing (3DP) and tissue engineering concepts have significantly contributed to our understanding of cell–cell and cell–extracellular matrix interactions in the cancer microenvironment. Moreover, 3D tumor models were used to study the therapeutic efficiency of anticancer drugs. The present study aims to provide an overview of applying the 3DP and tissue engineering concepts for cancer studies with suggestions for future research directions. The 3DP technologies being used for the fabrication of personalized DDS have been highlighted and the potential technical approaches and challenges associated with the fused deposition modeling, the inkjet-powder bed, and stereolithography as the most promising 3DP techniques for drug delivery purposes are briefly described. Then, the advances, challenges, and future perspectives in tissue-engineered cancer models for precision medicine are discussed. Overall, future advances in this arena depend on the continuous integration of knowledge from cancer biology, biofabrication techniques, multiomics and patient data, and medical needs to develop effective treatments ultimately leading to improved clinical outcomes.

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