The Physics of Microdroplets

The Physics of Microdroplets gives the reader the theoretical and numerical tools to understand, explain, calculate, and predict the often nonintuitive observed behavior of droplets in microsystems. Microdrops and interfaces are now a common feature in most fluidic microsystems, from biology, to biotechnology, materials science, 3D-microelectronics, optofluidics, and mechatronics. On the other hand, the behavior of droplets and interfaces in today's microsystems is complicated and involves complex 3D geometrical considerations. From a numerical standpoint, the treatment of interfaces separati

Computational Simulation of Interstitial Flow in Bioprinted 3D Tissue Constructs

Organ printing is a robotic computer-aided layer by layer additive biofabrication of 3D tissue and organ constructs using tissue spheroids as building blocks. It has been demonstrated that intraorgan branched vascular tree could be bioprinted inside 3D tissue and organ constructs. However, maturation of built-in branched vascular tree suitable for perfusion needs some time. In order to buy time necessary for maturation of branched vascular tree and maintain viability of bioprinted 3D tissue constructs an interstitial perfusion with special irrigation dripping bioreactor could be used. Computational simulations with using Surface Evolver software and Computational Fluid Dynamics software demonstrated that short term viability of bioprinted 3D tissue and organ constructs by interstitial flow is feasible.Published versio

Design, Physical Prototyping and Initial Characterization of “Lockyballs”

Directed tissue self-assembly or bottom-up modular approach in tissue biofabrication is an attractive and potentially superior alternative to a classic top-down solid scaffoldbased approach in tissue engineering. For example, rapidly emerging organ printing technology using self-assembling tissue spheroids as building blocks is enabling a computer-aided robotic bioprinting of 3D tissue constructs. However, achieving proper material properties while maintaining desirable geometry and shape of 3D bioprinted tissue engineered constructs using directed tissue self-assembly, is still a challenge. Proponents of directed tissue self-assembly see solution of this problem in developing methods of accelerated tissue maturation and/or using sacrificial temporal supporting of removable hydrogels. In the meantime, there is a growing consensus that a third strategy based on the integration of a directed tissue self-assembly approach with a conventional solid scaffold-based approach could be a potential optimal solution. We hypothesize that tissue spheroids with “velcro®-like” interlockable solid microscaffolds or simply “lockyballs” could enable the rapid in vivo biofabrication of 3D tissue constructs at desirable material properties and high initial cell density. Recently, biocompatible and biodegradable photo-sensitive biomaterials could be fabricated at nanoscale resolution using two-photon polymerization (2PP), a development rendering this technique a high potential to fabricate “velcro-like” interlockable microscaffolds. Here we report design studies, physical prototyping using 2PP and initial functional characterization of interlockable solid microscaffolds or so-called “lockyballs”. 2PP was used as a novel enabling platform technology for rapid bottom-up modular tissue biofabrication of interlockable constructs. The principle of lockable tissue spheroids fabricated using the described lockyballs as solid microscaffolds is characterized by attractive new functionalities such as lockability and tunable material properties of the engineered constructs. It is reasonable to predict that these building blocks create the basis for a development of a clinical in vivo rapid biofabrication approach and forms part of recent promising emerging bioprinting technologies

Biofabrication of human ASCs spheroid into lockyballs.

<p>Micro-molded resections showing (A, B, C) one, (D, E, F) two or (G, H, I) three lockyballs. Note that all spheroids are inside lockyballs. (D-I) Resections showing interlocking. (A, D, G) Light microscopy, (B, E, H) Green: autofluorescent lockyballs due to autofluorescence of photo-polymerized biomaterial (C, F, I) Merge of pictures: light microscopy, DAPI staining (blue), green. Bar size: 100 micrometers.</p