In this “From Academia” blog, we focus on a key ingredient for successful bioprinting, the bioinks. The first article is a recently published review article that will lay the foundation of various bioprinting methods as well as a special focus on the natural, synthetic, or hybrid materials used as bioinks. This article also addresses the challenges, limitations, and future directions concerning the bioprinting technique. This second article shows how bioprinting and organoid technology can be merged to generate centimeter-scale tissues that have self-organized features including lumens, branched vasculatures, and tubular intestinal epithelia with in vivo-like crypts and villus domains. This method could potentially be used to produce larger functional tissue with more geometry and cellular control. The third article introduced a new hydrogel bioink composed of partially digested, porcine cardiac decellularized extracellular matrix (cdECM), Laponite-XLG nanoclay, and poly(ethylene glycol)-diacrylate (PEG-DA). The researchers show that 3D printed constructs with this new bioink demonstrated shape fidelity, adaptability to different printing conditions, and high cell viability following extrusion and photo-polymerization, highlighting the potential for applications in modeling both healthy and fibrotic cardiac tissue. “From Academia” features recent, relevant, close to commercialization academic publications. Subjects include but not limited to healthcare 3D printing, 3D bioprinting, and related emerging technologies.
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– Authored by Dr. Roghayeh Khoeini Dr. Hamed Nosrati Dr. Abolfazl Akbarzadeh Dr. Aziz Eftekhari Dr. Taras Kavetskyy Prof. Rovshan Khalilov Dr. Elham Ahmadian Dr. Aygun Nasibova Dr. Pallab Datta Dr. Leila Roshangar Dr. Dante C. Deluca Dr. Soodabeh Davaran Prof. Magali Cucchiarini Prof. Ibrahim T. Ozbolat. Advanced Nanobiomed Research. March 30 2021
Bioprinting offers tremendous potential in the fabrication of functional tissue constructs for replacement of damaged or diseased tissues. Among other fabrication methods used in tissue engineering, bioprinting provides accurate control over the construct’s geometric and compositional attributes using an automated approach.
Bioinks are composed of the hydrogel material and living cells that are critical process variables in the fabrication of functional, mechanically robust constructs. Appropriate cells can be encapsulated in bioinks to create functional tissue structures. Ideal bioinks are required to undergo a sol‐gel transition consuming minimal processing time, and a plethora of chemical and physical crosslinking mechanisms are generally exploited to achieve high shape fidelity and construct stability. On the other hand, crosslinking of hydrogel material at rapid rates can cause nozzle clogging, and hence, optimization of the bioink is often necessary. Bioinks can be formulated using natural or synthetic biomaterials, alone or in combination of these biomaterials.
In this review, we discuss the various bioprinting methods and analyze the natural, synthetic, or hybrid materials used as bioinks and appraise the challenges, limitations, and future directions concerning the bioprinting technique.
Keywords: bioink, bioprinting, hybrid materials, tissue engineering
– Authored by Jonathan A. Brassard, Mike Nikolaev, Tania Hübscher, Moritz Hofer & Matthias P. Lutolf. Nature Materials, September 21 2020
Bioprinting promises enormous control over the spatial deposition of cells in three dimensions but current approaches have had limited success at reproducing the intricate micro-architecture, cell-type diversity and function of native tissues formed through cellular self-organization. We introduce a three-dimensional bioprinting concept that uses organoid-forming stem cells as building blocks that can be deposited directly into extracellular matrices conducive to spontaneous self-organization. By controlling the geometry and cellular density, we generated centimetre-scale tissues that comprise self-organized features such as lumens, branched vasculature and tubular intestinal epithelia with in vivo-like crypts and villus domains. Supporting cells were deposited to modulate morphogenesis in space and time, and different epithelial cells were printed sequentially to mimic the organ boundaries present in the gastrointestinal tract. We thus show how biofabrication and organoid technology can be merged to control tissue self-organization from millimetre to centimetre scales, opening new avenues for drug discovery, diagnostics and regenerative medicine.
Keywords: Assay systems, bioinspired materials, stem-cell biotechnology, tissue engineering, tissues
3D bioprinting of mechanically tuned bioinks derived from cardiac decellularized extracellular matrix
– Authored by Yu Jung Shin, Ryan T. Shafranek, Jonathan H. Tsui, Jelisha Walcott, Alshakim Nelson, Deok-Ho Kim. Acta Biomaterialia. January 1 2021
3D bioprinting is a powerful technique for engineering tissues used to study cell behavior and tissue properties in vitro. With the right formulation and printing parameters, bioinks can provide native biological and mechanical cues while allowing for versatile 3D structures that recapitulate tissue-level organization.
Bio-based materials that support cellular adhesion, differentiation, and proliferation – including gelatin, collagen, hyaluronic acid, and alginate – have been successfully used as bioinks. In particular, decellularized extracellular matrix (dECM) has become a promising material with the unique ability to maintain both biochemical and topographical micro-environments of native tissues. However, dECM has shown technical limitations for 3D printing (3DP) applications posed by its intrinsically low mechanical stability. Herein, we report hydrogel bioinks composed of partially digested, porcine cardiac decellularized extracellular matrix (cdECM), Laponite-XLG nanoclay, and poly(ethylene glycol)-diacrylate (PEG-DA).
The Laponite facilitated extrusion-based 3DP, while PEG-DA enabled photo-polymerization after printing. Improving upon previously reported bioinks derived from dECM, our bioinks combine extrudability, shape fidelity, rapid cross-linking, and cytocompatibility in a single formulation (> 97% viability of encapsulated human cardiac fibroblasts and > 94% viability of human induced pluripotent stem cell derived cardiomyocytes after 7 days). The compressive modulus of the cured hydrogel bioinks was tunable from 13.4-89 kPa by changing the concentration of PEG-DA in the bioink formulation. Importantly, this span of mechanical stiffness encompasses ranges of tissue stiffness from healthy (compressive modulus ~5-15 kPa) to fibrotic (compressive modulus ~30-100 kPa) cardiac tissue states.
The printed constructs demonstrated shape fidelity, adaptability to different printing conditions, and high cell viability following extrusion and photo-polymerization, highlighting the potential for applications in modeling both healthy and fibrotic cardiac tissue.
Keywords: Direct-ink writing,Bioinks,Decellularized extracellular matrix,Cardiac tissue engineering