Cell Printing Research Articles

Smart Design for Hybrid Bioprinting of Scalable and Viable Tissue Constructs.

Hybrid bioprinting uses sequential printing of melt-extruded biodegradable thermoplastic polymer and cell-encapsulated bioink in a predesigned manner using high- and low-temperature print heads for the fabrication of robust three-dimensional (3D) biological constructs. However, the high-temperature print head and melt-extruded polymer cause irreversible thermal damage to the bioprinted cells, and it affects viability and functionality of 3D bioprinted biological constructs. Thus, there is an urgent need to develop innovative approaches to protect the bioprinted cells, coming into contact or at close proximities to the melt-extruded thermoplastic polymer and the high-temperature print head during hybrid bioprinting. Therefore, this study investigated the potential of iterating the structural architecture pattern (SAP) of melt-printed thermoplastic layers and the cell printing pattern (CPP) to protect the cells from temperature-associated damage during hybrid bioprinting. A novel SAP for printing the thermoplastic polymer and an associated CPP for minimizing thermal damage to the 3D bioprinted construct have been developed. The newly developed SAP- and CPP-based hybrid bioprinted biological constructs showed significantly low thermal damage compared to conventionally hybrid bioprinted biological constructs. The results from this study suggest that the newly developed SAP and CPP can be an improved hybrid bioprinting strategy for developing living constructs at the human scale.

A click chemistry-mediated all-peptide cell printing hydrogel platform for diabetic wound healing

High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.

Recent Progress of 3D Printing of Polymer Electrolyte Membrane-Based Fuel Cells for Clean Energy Generation.

This review summarizes recent advances in the application of 3D printing (additive manufacturing) for the fabrication of various components of hydrogen fuel cells with a polymer electrolyte membrane (HFC-PEMs). This type of fuel cell is an example of green renewable energy, but its active implementation into the real industry is fraught with a number of problems, including rapid degradation and low efficiency. The application of 3D printing is promising for improvement in HFC-PEM performance due to the possibility of creating complex geometric shapes, the exact location of components on the substrate, as well as the low-cost and simplicity of the process. This review examines the use of various 3D printing techniques, such as inkjet printing, fused deposition modeling (FDM) and stereolithography, for the production/modification of electrodes, gas diffusion and catalyst layers, as well as bipolar plates. In conclusion, the challenges and possible solutions of the identified drawbacks for further development in this field of research are discussed. It is expected that this review article will benefit both representatives of applied science interested in specific engineering solutions and fundamental science aimed at studying the processes occurring in the fuel cell.

Over 18% Efficiency Ternary Organic Solar Cells with 300nm Thick Active Layer Enabled by an Oligomeric Acceptor.

The development of high-efficiency thickness-insensitive organic solar cells (OSCs) is crucially important for the mass production of solar panels. However, increasing the active layer thickness usually induces a substantial loss in efficiency. Herein, a ternary strategy in which an oligomer DY-TF is incorporated into PM6:L8-BO system as a guest component is adopted to break this dilemma. The S···F intramolecular noncovalent interactions in the backbone endow DY-TF with a high planarity. Upon the addition of DY-TF, the crystallinity of the blend is effectively improved, leading to increased charge carrier mobility, which is highly desirable in the fabrication of thick-film devices. As a result, thin-film PM6:L8-BO:DY-TF-based device (110nm) shows a power conversion efficiency (PCE) of 19.13%. Impressively, when the active layer thickness increases to 300nm, an efficiency of 18.23% (certified as 17.8%) is achieved, representing the highest efficiency reported for 300 nm thick OSCs thus far. Additionally, blade-coated thick device (300nm) delivers a promising PCE of 17.38%. This work brings new insights into the construction of efficient OSCs with high thickness tolerance, showing great potential for roll-to-roll printing of large-area solar cells.

Crystallization Control for Ambient Printed FA-Based Lead Triiodide Perovskite Solar Cells.

Upscalable printing of high-performance and stable perovskite solar cells (PSCs) is highly desired for commercialization. However, the efficiencies of printed PSCs lag behind those of their lab-scale spin-coated counterparts owing to the lack of systematic understanding and control over perovskite crystallization dynamics. Here, the controlled crystallization dynamics achieved using an additive 1-butylpyridine tetrafluoroborate (BPyBF4 ) for high-quality ambient printed α-formamidinium lead triiodide (FAPbI3 ) perovskite films are reported. Using in situ grazing-incidence wide-angle X-ray scattering and optical diagnostics, the spontaneous formation of α-FAPbI3 from precursors during printing without the involvement of δ-FAPbI3 is demonstrated. The addition of BPyBF4 delays the crystallization onset of α-FAPbI3 , enhances the conversion from sol-gel to perovskite, and reduces stacking defects during printing. Therefore, the altered crystallization results in fewer voids, larger grains, and less trap-induced recombination loss within printed films. The printed PSCs yield high power conversion efficiencies of 23.50% and 21.60% for a0.09 cm-2 area device and a 5cm × 5cm-area module, respectively. Improved device stability is further demonstrated, i.e., approximately 94% of the initial efficiency is retained for over 2400h under ambient conditions without encapsulation. This study provides an effective crystallization control method for the ambient printing manufacture of large-area high-performance PSCs.

Rise of tissue- and species-specific 3D bioprinting based on decellularized extracellular matrix-derived bioinks and bioresins

Thanks to its natural complexity and functionality, decellularized extracellular matrix (dECM) serves as an excellent foundation for creating highly cell-compatible bioinks and bioresins. This enables the bioprinted cells to thrive in an environment that closely mimics their native ECM composition and offers customizable biomechanical properties. To formulate dECM bioinks and bioresins, one must first pulverize and/or solubilize the dECM into non-crosslinked fragments, which can then be chemically modified as needed. In bioprinting, the solubilized dECM-derived material is typically deposited and/or crosslinked in a layer-by-layer fashion to build 3D hydrogel structures. Since the introduction of the first liver-derived dECM-based bioinks, a wide variety of decellularized tissue have been employed in bioprinting, including kidney, heart, cartilage, and adipose tissue among others. This review aims to summarize the critical steps involved in tissue-derived dECM bioprinting, starting from the decellularization of the ECM to the standardized formulation of bioinks and bioresins, ultimately leading to the reproducible bioprinting of tissue constructs. Notably, this discussion also covers photocrosslinkable dECM bioresins, which are particularly attractive due to their ability to provide precise spatiotemporal control over the gelation in bioprinting. Both in extrusion printing and vat photopolymerization, there is a need for more standardized protocols to fully harness the unique properties of dECM-derived materials. In addition to mammalian tissues, the most recent bioprinting approaches involve the use of microbial extracellular polymeric substances in bioprinting of bacteria. This presents similar challenges as those encountered in mammalian cell printing and represents a fascinating frontier in bioprinting technology.

Three-Dimensional Bioprinting in Soft Tissue Engineering for Plastic and Reconstructive Surgery.

Skeletal muscle tissue engineering (TE) and adipose tissue engineering have undergone significant progress in recent years. This review focuses on the key findings in these areas, particularly highlighting the integration of 3D bioprinting techniques to overcome challenges and enhance tissue regeneration. In skeletal muscle TE, 3D bioprinting enables the precise replication of muscle architecture. This addresses the need for the parallel alignment of cells and proper innervation. Satellite cells (SCs) and mesenchymal stem cells (MSCs) have been utilized, along with co-cultivation strategies for vascularization and innervation. Therefore, various printing methods and materials, including decellularized extracellular matrix (dECM), have been explored. Similarly, in adipose tissue engineering, 3D bioprinting has been employed to overcome the challenge of vascularization; addressing this challenge is vital for graft survival. Decellularized adipose tissue and biomimetic scaffolds have been used as biological inks, along with adipose-derived stem cells (ADSCs), to enhance graft survival. The integration of dECM and alginate bioinks has demonstrated improved adipocyte maturation and differentiation. These findings highlight the potential of 3D bioprinting techniques in skeletal muscle and adipose tissue engineering. By integrating specific cell types, biomaterials, and printing methods, significant progress has been made in tissue regeneration. However, challenges such as fabricating larger constructs, translating findings to human models, and obtaining regulatory approvals for cellular therapies remain to be addressed. Nonetheless, these advancements underscore the transformative impact of 3D bioprinting in tissue engineering research and its potential for future clinical applications.

Fine‐tuning Dynamic Cross–linking for Enhanced 3D Bioprinting of Hyaluronic Acid Hydrogels

Abstract3D bioprinting of stem cells shows promise for medical applications, but the development of an efficient bioink remains a challenge. Recently, the emergence of dynamically cross–linked hydrogels has advanced this field to obtain self‐healing materials. However, more advanced bioinks are needed that display optimum gelling kinetics, viscoelasticity, shear‐thinning property, structural fidelity, and hold the printed structures sufficiently long enough that allow maturation of the new tissue. Here, a novel extracellular matrix‐based bioink for human mesenchymal stem cells (hMSCs) is presented. Hyaluronic acid (HA) is modified with cysteine and aldehyde functional groups, creating hydrogels with dual cross–linking of disulfide and thiazolidine products. The investigation demonstrates that this cross–linking significantly improves hydrogel stability and biological properties. The bioink exhibits fast gelation kinetics, shear‐thinning, shape‐maintaining properties, high cell survival after printing with >2‐fold increase in stemness marker (OCT3/4 and NANOG), and supports cell proliferation and migration. Disulfide cross–linking contributes to self‐healing and cell migration, while thiazolidine cross–linking reduces gelation time, enhances long‐term stability, and supports cell proliferation. Overall, the HA‐based bioink fulfills the requirements for successful 3D printing of stem cells, providing a promising solution for cell therapy and regenerative medicine.

A Pillar and Perfusion Plate Platform for Robust Human Organoid Culture and Analysis.

Human organoids have the potential to revolutionize in vitro disease modeling by providing multicellular architecture and function that are similar to those in vivo. This innovative and evolving technology, however, still suffers from assay throughput and reproducibility to enable high-throughput screening (HTS) of compounds due to cumbersome organoid differentiation processes and difficulty in scale-up and quality control. Using organoids for HTS is further challenged by the lack of easy-to-use fluidic systems that are compatible with relatively large organoids. Here, these challenges are overcome by engineering "microarray three-dimensional (3D) bioprinting" technology and associated pillar and perfusion plates for human organoid culture and analysis. High-precision, high-throughput stem cell printing, and encapsulation techniques are demonstrated on a pillar plate, which is coupled with a complementary deep well plate and a perfusion well plate for static and dynamic organoid culture. Bioprinted cells and spheroids in hydrogels are differentiated into liver and intestine organoids for in situ functional assays. The pillar/perfusion plates are compatible with standard 384-well plates and HTS equipment, and thus may be easily adopted in current drug discovery efforts.

Rapidly Direct Laser 3D Printing of High-Performance Protonic Ceramic Fuel Cells

Fuel cells with a dense ionic conducting electrolyte layer sandwiched between two porous electrode layers are one of the most efficient fuel-to-electricity energy conversion devices. Their reversible operation can also efficiently electrolyze water to hydrogen, reduce carbon dioxide to fuels, synthesize ammonia, upgrade fuels, and store energy on large scales. Compared with the popular low-temperature (~80 oC) proton exchange/polymer electrolyte membrane fuel cells and the high-temperature (700-1000 oC) oxygen ion-conducting solid oxide fuel cells (SOFCs), initially used in electric vehicles, auxiliary powers, power plants, and hydrogen electrolyzers, the rising star of protonic ceramic fuel cells (PCFCs) based on proton conducting oxide electrolytes offers excellent suitability for operating at 400-700 oC, the optimum temperature range for electrochemical energy devices, enabling extensive superiorities (high efficiency and performance, long thermal and chemical stabilities, flexible fuels, and cost-effective compatible materials) compared to their counterparts. In recent ten years, many high-performance PCFCs have been reported. However, most performances were achieved using small-area button cells (<0.5cm2) fabricated using spin coating, drop coating, manual brushing, and screen printing of electrolytes on the dry-pressed anode supports, followed by co-firing. There are challenges to transferring the excellent microstructures and materials chemistries/properties obtained from small-area cells to large-area cells and stacks. Furthermore, the decrease in cell component layer thickness for high volumetric cell performance and the requirement for more efficient, faster, and more cost-effective manufacturing motivated the advanced manufacturing of PCFCs.This work will focus on the direct laser 3D printing (DL3DP) of PCFCs performed at Clemson University. The DL3DP integrated 3D printing (microextrusion and ultrasonic spraying) and laser processing (drying, sintering, and machining), allowing for manufacturing PCFC components, single cells, and stacks with the desired microstructures and geometries irrelevant to the area. The DL3DP could rapidly and cost-effectively manufacture PCFCs without conventional long-term furnace processing. The processing speed could be 2 orders of magnitude faster than the conventional tape-casting and furnace co-firing method. The achieved cells and stacks showed excellent fuel cell performance and less dependence on the effective area. The cells showed peak power densities 1.6-2.6 times that of the conventionally processed samples. The stacks demonstrated a peak power of 7 W and constant power outputs of 0.5-3.1 W for 110-260 hours. This DL3DP can be expanded to manufacturing other heterogeneous ceramics for energy conversion and storage devices. Figure 1

3D Cell Printing of Advanced Vascularized Proximal Tubule-on-a-Chip for Drug Induced Nephrotoxicity Advancement.

Renal dysfunction due to drug-induced nephrotoxicity (DIN) affects >20% of the adult population worldwide. The vascularized proximal tubule is a complex structure that is often the primary site of drug-induced kidney injury. Herein, a vascularized proximal tubule-on-a-chip (Vas-POAC) was fabricated, demonstrating improved physiological emulation over earlier single-cell proximal tubule models. A perfusable model of vascularized proximal tubules permits the growth and proliferation of renal proximal tubule cells and adjacent endothelial cells under various conditions. An in vitro Vas-POAC showed mature expressions of the tubule and endothelial cell markers in the mature epithelium and endothelium lumens after 7 days of culture. Expression in the mature proximal tubule epithelium resembled the polarized expression of sodium-glucose cotransporter-2 and the de novo synthesis of ECM proteins. These perfusable Vas-POACs display significantly improved functional properties relative to the proximal tubules-on-a-chip (POAC), which lacks vascular components. Furthermore, the developed Vas-POAC model evaluated the cisplatin-induced nephrotoxicity and revealed enhanced drug receptivity compared to POAC. We further evaluated the capability of the developed proximal tubule model to act as a functional platform that targets screening drug doses that can cause renal proximal tubule injury in adults. Thus, our cell-printed models may prove valuable for screening, thoughtful mechanistic investigations of DIN, and discovery of drugs that interfere with tubule formation.

Trackable and highly fluorescent nanocellulose-based printable bio-resins for image-guided tissue regeneration

Dynamic tracking of cell migration during tissue regeneration remains challenging owing to imaging techniques that require sophisticated devices, are often lethal to healthy tissues. Herein, we developed a 3D printable non-invasive polymeric hydrogel based on 2,2,6,6-(tetramethylpiperidin-1-yl) oxyl (TEMPO)-oxidized nanocellulose (T-CNCs) and carbon dots (CDs) for the dynamic tracking of cells. The as-prepared T-CNC@CDs were used to fabricate a liquid bio-resin containing gelatin methacryloyl (GelMA) and polyethylene glycol diacrylate (GPCD) for digital light processing (DLP) bioprinting. The shear-thinning properties of the GPCD bio-resin were further improved by the addition of T-CNC@CDs, allowing high-resolution 3D printing and bioprinting of human cells with higher cytocompatibility (viability ∼95 %). The elastic modulus of the printed GPCD hydrogel was found to be ∼13 ± 4.2 kPa, which is ideal for soft tissue engineering. The as-fabricated hydrogel scaffold exhibited tunable structural color property owing to the addition of T-CNC@CDs. Owing to the unique fluorescent property of T-CNC@CDs, the human skin cells could be tracked within the GPCD hydrogel up to 30 days post-printing. Therefore, we anticipate that GPCD bio-resin can be used for 3D bioprinting with high structural stability, dynamic tractability, and tunable mechanical stiffness for image-guided tissue regeneration.

Synthetic Cell Armor Made of DNA Origami.

The bioengineering applications of cells, such as cell printing and multicellular assembly, are directly limited by cell damage and death due to a harsh environment. Improved cellular robustness thus motivates investigations into cell encapsulation, which provides essential protection. Here we target the cell-surface glycocalyx and cross-link two layers of DNA nanorods on the cellular plasma membrane to form a modular and programmable nanoshell. We show that the DNA origami nanoshell modulates the biophysical properties of cell membranes by enhancing the membrane stiffness and lowering the lipid fluidity. The nanoshell also serves as armor to protect cells and improve their viability against mechanical stress from osmotic imbalance, centrifugal forces, and fluid shear stress. Moreover, it enables mediated cell-cell interactions for effective and robust multicellular assembly. Our results demonstrate the potential of the nanoshell, not only as a cellular protection strategy but also as a platform for cell and cell membrane manipulation.

LIFT of cell spheroids: Proof of concept

The application of spheroids in tissue engineering has a number of advantages over conventional cell suspensions and 2D cultures. One of the methods for tissue and organ fabrication from spheroids is bioprinting. As one of bioprinting methods, laser-induced forward transfer (LIFT) has received much attention in terms of cell printing, while its potential has not been realized for spheroid patterning yet. In this paper, the authors have shown for the first time the practical applicability of LIFT for spheroid transfer with high survival rates and printing precision. For this, a special optical device, a piShaper, was used to change the laser energy distribution to non-Gaussian profile which allowed for mitigating the negative effects of laser radiation on the spheroids during LIFT. The authors showed that non-Gaussian energy distribution in the laser spot in the form of double ring led to higher post-printing viability of spheroids than in case of conventional Gaussian energy distribution in laser beam. Subsequently, using the double ring laser spot geometry, the spheroids were bioprinted in the form of simple geometric figures: line, triangle, and square. Overall, LIFT bioprinting of spheroids has demonstrated a strong potential as the precise, safe, and reproducible method for biofabrication that can be potentially used for making tissue-engineered bioequivalents or building specific organ-on-a-chip platforms.

A Systematic Review on Polyester Scaffolds in Dental Three-dimensional Cell Printing: Transferring Art from the Laboratories to the Clinics.

The purpose of this systematic review is to describe developments in three-dimensional (3D) cell printing in the formation of dental pulp tissue using polyester as a scaffold to revitalize the damaged dental pulp tissue. A literature search for all the data published in PubMed and Google Scholar from January 2000 to April 2022 was conducted. Articles with the keywords 3D cell printing, scaffolds, polyester, dental pulp, and dentistry were used. Inclusion criteria consisted of any publication in electronic or print media directly studying or commenting on the use of polyester scaffolds in 3D cell printing technology in the regeneration of dental pulp. A total of 528 articles were selected, of which 27 duplicates and 286 irrelevant articles were discarded. A total of 215 articles were finally included in the systematic review. For dental pulp regeneration, several scaffolds have been discovered to be appealing. Polylactic acid (PLA), polyglycolic acid (PGA), and their copolymers are nontoxic and biocompatible synthetic polyesters that degrade by hydrolysis and have received Food and Drug Administration (FDA) approval for a variety of applications. This review paper is intended to spark new ideas for using a certain scaffold in a specific regenerative approach to produce the desired pulp-dentin complex.

P41: 4D Manufacturing: Immunoprotective Materials for Islet Tissue Patches in Cell-Based Diabetes Treatments

Purpose: In order to cure diabetes on a large scale, researchers are working to develop insulin-producing cells differentiated from human pluripotent stem cells, encapsulating the tissues to protect the cells from immune attack, and implanting the cells for regulated insulin secretion. This project explored the synthesis and in vivo performance of a 4D biomaterial intended to protect implanted insulin-producing cells in the body. 3D printing of insulin-producing cells encapsulated within the biomaterial with additional timed-release anti-inflammatory agents enabled complex, personalized shapes and a 4D functional material. Methods: Anti-inflammatory agents were functionalized with varying permanent and degradable linkages to achieve a range of timed-release therapeutics to prevent immune system-mediated rejection. The molecules were crosslinked with a multi-arm polyethylene glycol (PEG) material in the subcutaneous space of immunocompetent C57BL/6 mice. After 30 days, tissue slices of the explant were examined using H&E staining revealing the thickness of biological encapsulation compared to alginate controls. Results: PEG-based implants with acetal linkages enabling the slow release (~30 days) of anti-inflammatory agents achieved the thinnest layer of biological encapsulation compared to the controls. Summary: Collectively, the described 4D biomaterial with other novel approaches and tools will enable the investigation of survival and function of a stem cell-based therapy for diabetes that could ultimately allow patients to live a diabetes-free lifestyle.

Microgel-Extracellular Matrix Composite Support for the Embedded 3D Printing of Human Neural Constructs.

The embedded 3D printing of cells inside a granular support medium has emerged in the past decade as a powerful approach for the freeform biofabrication of soft tissue constructs. However, granular gel formulations have been restricted to a limited number of biomaterials that allow for the cost-effective generation of large amounts of hydrogel microparticles. Therefore, granular gel support media have generally lacked the cell-adhesive and cell-instructive functions found in the native extracellular matrix (ECM). To address this, a methodology has been developed for the generation of self-healing annealable particle-extracellular matrix (SHAPE) composites. SHAPE composites consist of a granular phase (microgels) and a continuous phase (viscous ECM solution) that, together, allow for both programmable high-fidelity printing and an adjustable biofunctional extracellular environment. This work describes how the developed methodology can be utilized for the precise biofabrication of human neural constructs. First, alginate microparticles, which serve as the granular component in the SHAPE composites, are fabricated and combined with a collagen-based continuous component. Then, human neural stem cells are printed inside the support material, followed by the annealing of the support. The printed constructs can be maintained for weeks to allow the differentiation of the printed cells into neurons. Simultaneously, the collagen continuous phase allows for axonal outgrowth and the interconnection of regions. Finally, this works provides information on how to perform live-cell fluorescence imaging and immunocytochemistry to characterize the 3D-printed human neural constructs.

Evolution of bioprinting and current applications.

Bioprinting is a very useful tool that has a huge application potential in different fields of science and biotechnology. In medicine, advances in bioprinting are focused on the printing of cells and tissues for skin regeneration and the manufacture of viable human organs, such as hearts, kidneys, and bones. This review provides a chronological overview of some of the most relevant developments of bioprinting technique and its current status. A search was carried out in SCOPUS, Web of Science, and PubMed databases, and a total of 31,603 papers were found, of which 122 were finally chosen for analysis. These articles cover the most important advances in this technique at the medical level, its applications, and current possibilities. Finally, the paper ends with conclusions about the use of bioprinting and our expectations of this technique. This paper presents a review on the tremendous progress of bioprinting from 1998 to the present day, with many promising results indicating that our society is getting closer to achieving the total reconstruction of damaged tissues and organs and thus solving many healthcare-related problems, including the shortage of organ and tissue donors.

High Performing Inverted Flexible Perovskite Solar Cells via Solution Phase Deposition of Yttrium-Doped SnO2 Directly on Perovskite

Solution processing of flexible perovskite solar cells (f-PSCs) provides an avenue for scalable, high-throughput printing of lightweight, scalable, and cost-effective flexible solar cells. However, the deposition of fully solution-processed metal oxide charge transport layers on perovskites has been limited by solvent incompatibilities and high processing temperatures for metal oxide nanoparticles. In this study, we present high-performance, inverted f-PSCs from the direct deposition of yttrium-doped SnO2 nanoparticles functionalized with acetate on top of perovskite as an ink in anhydrous ethanol via blade coating. Yttrium doping improved device performance by improving the charge extraction with a decreased series resistance leading to improvements in the open-circuit voltage and fill factor. The champion power conversion efficiency for 0.1 cm2 devices increased from 14.3% for undoped SnO2 to 16.5% with 2% Y:SnO2 doping, which is unprecedented for f-PSCs on ITO-PET substrates employing SnO2 as an ETL.

Visible light-crosslinkable tyramine-conjugated alginate-based microgel bioink for multiple cell-laden 3D artificial organ

While the natural carbohydrate alginate has enabled effective three-dimensional (3D) extrusion bioprinting, it still suffers from some issues such as low printability and resolution and limited cellular function due to ionic crosslinking dependency. Here, we prepared a harmless visible light-based photocrosslinkable alginate by chemically bonding tyrosine-like residues onto alginate chains to propose a new microgel manufacturing system for the development of 3D-printed bioinks. The photocrosslinkable tyramine-conjugated alginate microgel achieved both higher cell viability and printing resolution compared to the bulk gel form. This alginate-based jammed granular microgel bioink showed excellent 3D bioprinting ability with maintained structural stability. As a biocompatible material, the developed multiple cell-loaded photocrosslinkable alginate-based microgel bioink provided excellent proliferation and migration abilities of laden living cells, providing an effective strategy to construct implantable functional artificial organ structures for 3D bioprinting-based tissue engineering.