Each year worldwide millions of people suffer from organ failures that can only be treated by organ transplant that worsens with a shortage of donors. Research in tissue engineering (TE) directed towards organ printing (OP) provide us with options that hold a direct advantage over other therapies (drug) in offering a permanent solution by creating artificial transplantable organs and tissues. Based on bottom-up approaches, various micro-nano technologies using hydrogels, offer multiple options, which override the limitations from biodegradable solid scaffold approach. Current OP technologies, following the layer-by-layer assembly approach, combine biocompatible materials, cells and supporting components with suitable additive robotic biofabrication techniques. Though they have resulted in successful engineering of organs such as skin, liver, kidney to name some,it is still a challenge to produce them using entirely cell friendly conditions with an inexpensive methodology to expand the scope of experiments, visualization and produce TE organs. My research aims in establishing a simple, cheap and cell friendly process for constructing 3D functional living tissues as a viable alternative. An inspiring idea based on, merging macro-micro-nano scale technologies, using perfusion-based LbL technique (PLbL)1-3 combined with simple cell encapsulation technique4,5 offers us with a unique multipurpose 3D setup. This approach produces 3D constructs (macro) by assembling cell encapsulated building blocks (micro) that are held together by multilayers (nano), thereby combining the individual advantages of polyelectrolyte LbL and bioencapsulation using hydrogels. Coating single bioencapsulated spheres with multilayers yield polyelectrolyte multilayer capsules that show better cell viability due to efficient diffusion of nutrients, oxygen, and cell metabolites because of liquified core enclosed within a permselective membrane.6,7 Despite this, their utility is limited because of the difficulty to assemble or pattern them over length scales for mimicking the complex 3D architecture and organization of native tissues. Brief highlights of our technique include, novelty: real time binding/sticking feature of multilayers, advantages: desktop process, self-assembly without using binders/ crosslinking approaches, freeform fabrication into different shapes/sizes, eliminating prefabrication of 3D core, less volume and time than conventional techniques, customized building blocks, limited use of molds enabling continuous and stable multilayers over contours, high aspect ratio, compartmentalization, decisively switching internal cell microenvironment from solid to liquefied state. This fabricated 3D construct, exhibiting these features and with unlimited freedom to modify, ensures multipurpose applications for OP which can also serve as studying intricate disease model and with easy translation to produce novel drug delivery systems for improving healthcare.
By Dr Praveen Sher
Though they have resulted in successful engineering of organs such as skin, liver, kidney to name some,it is still a challenge to produce them using entirely cell friendly conditions with an inexpensive methodology to expand the scope of experiments, visualization and produce TE organs. My research aims in establishing a simple, cheap and cell friendly process for constructing 3D functional living tissues as a viable alternative”
- P. Sher, C. Custódio, J. Mano, Layer-By-Layer Technique for Producing Porous Nanostructured 3D Constructs Using Moldable Freeform Assembly of Spherical Templates, Small, 6 (2010). 2644-48.
- P. Sher, J. Mano, Multilayers as 3D nanostructured porous constructs, Bioinspired, Biomimetic and Nanobiomaterials, 1 (2012). 245-51.
- J. Silva, N. Georgi, R. Costa, P. Sher, R. Reis, C. Blitterswijk, M. Karperien, J. Mano, Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering, PLoS ONE,8 (2013) e55451.
- P. Sher, C. Correia, R. Costa, J. Mano, Compartmentalized Bioencapsulated Liquefied 3D Macro-Construct by Perfusion-Based Layer-by-Layer Technique, RSC Adv., 5 (2015) 2511-16.
- P. Sher, S. Oliveira, J. Borges, J. Mano, Assembly of cell-laden hydrogel fiber into non-liquefied and liquefied 3D spiral constructs by perfusion-based layer-by-layer technique, Biofabrication, 7 (2015) 011001.
- N. Costa, P. Sher, J. Mano, Liquefied Capsules Coated with Multilayered Polyelectrolyte Films for Cell Immobilization, Adv. Eng. Mater., 13 (2011) B218-24.
- C. Correia, P. Sher, R. Reis, J. Mano, Liquified chitosan–alginate multilayer capsules incorporating poly( l -lactic acid) microparticles as cell carriers, Soft Matter, 9 (2013) 2125-30.