Search for: All records

Abstract Embedded ink writing (EIW) is an emerging 3D printing technique that fabricates complex 3D structures from various biomaterial inks but is limited to a printing speed of ∼10 mm s⁻¹due to suboptimal rheological properties of particulate‐dominated yield‐stress fluids when used as liquid baths. In this work, a particle‐hydrogel interactive system to design advanced baths with enhanced yield stress and extended thixotropic response time for realizing high‐speed EIW is developed. In this system, the interactions between particle additive and three representative polymeric hydrogels enable the resulting nanocomposites to demonstrate different rheological behaviors. Accordingly, the interaction models for the nanocomposites are established, which are subsequently validated by macroscale rheological measurements and advanced microstructure characterization techniques. Filament formation mechanisms in the particle‐hydrogel interactive baths are comprehensively investigated at high printing speeds. To demonstrate the effectiveness of the proposed high‐speed EIW method, an anatomic‐size human kidney construct is successfully printed at 110 mm s⁻¹, which only takes ∼4 h. This work breaks the printing speed barrier in current EIW and propels the maximum printing speed by at least 10 times, providing an efficient and promising solution for organ reconstruction in the future. 

Abstract Granular hydrogels composed of hydrogel microparticles are promising candidates for 3D bioprinting due to their ability to protect encapsulated cells. However, to achieve high print fidelity, hydrogel microparticles need to jam to exhibit shear‐thinning characteristics, which is crucial for 3D printing. Unfortunately, this overpacking can significantly impact cell viability, thereby negating the primary advantage of using hydrogel microparticles to shield cells from shear forces. To overcome this challenge, a novel solution: a biphasic, granular colloidal bioink designed to optimize cell viability and printing fidelity is introduced. The biphasic ink consists of cell‐laden polyethylene glycol (PEG) hydrogel microparticles embedded in a continuous gelatin methacryloyl (GelMA)‐nanosilicate colloidal network. Here, it is demonstrated that this biphasic bioink offers outstanding rheological properties, print fidelity, and structural stability. Furthermore, its utility for engineering complex tissues with multiple cell types and heterogeneous microenvironments is demonstrated, by incorporating β‐islet cells into the PEG microparticles and endothelial cells in the GelMA‐nanosilicate colloidal network. Using this approach, it is possible to induce cell patterning, enhance vascularization, and direct cellular function. The proposed biphasic bioink holds significant potential for numerous emerging biomedical applications, including tissue engineering and disease modeling. 

Abstract Herein, a method that uses direct‐ink‐write printing to fabricate engineering living materials (ELMs) that respond by undergoing a programmed shape change in response to specific molecules is reported. Stimuli‐responsiveness is imparted to ELMs by integrating genetically engineered yeast that only proliferate in the presence of specific biomolecules. This proliferation, in turn, leads to a shape change in the ELM in response to that biomolecule. These ELMs are fabricated by coprinting bioinks that contain multiple yeast strains. Locally, cellular proliferation leads to controllable shape change of the material resulting in up to a 370% increase in volume. Globally, the printed 3D structures contain regions of material that increase in volume and regions that do not under a given set of conditions, leading to programmable changes in form in response to target amino acids and nucleotides. Finally, this printing method is applied to design a reservoir‐based drug delivery system for the on‐demand delivery of a model drug in response to a specific biomolecule. 

Abstract Bioprinting is an emerging approach for fabricating cell‐laden 3D scaffolds via robotic deposition of cells and biomaterials into custom shapes and patterns to replicate complex tissue architectures. Bioprinting uses hydrogel solutions called bioinks as both cell carriers and structural components, requiring bioinks to be highly printable while providing a robust and cell‐friendly microenvironment. Unfortunately, conventional hydrogel bioinks have not been able to meet these requirements and are mechanically weak due to their heterogeneously crosslinked networks and lack of energy dissipation mechanisms. Advanced bioink designs using various methods of dissipating mechanical energy are aimed at developing next‐generation cellularized 3D scaffolds to mimic anatomical size, tissue architecture, and tissue‐specific functions. These next‐generation bioinks need to have high print fidelity and should provide a biocompatible microenvironment along with improved mechanical properties. To design these advanced bioink formulations, it is important to understand the structure–property–function relationships of hydrogel networks. By specifically leveraging biophysical and biochemical characteristics of hydrogel networks, high performance bioinks can be designed to control and direct cell functions. In this review article, current and emerging approaches in hydrogel design and bioink reinforcement techniques are critically evaluated. This bottom‐up perspective provides a materials‐centric approach to bioink design for 3D bioprinting. 

Abstract A nanoengineered bioink loaded with therapeutic proteins is designed to direct cell function in a 3D printed construct. The bioink is developed from a hydrolytically degradable polymer and 2D synthetic nanoparticle. The synthesis of poly(ethylene glycol)‐dithiothreitol (PEGDTT) via a Michael‐like step growth polymerization results in acrylate terminated degradable macromer. The addition of 2D nanosilicates to PEGDTT results in formation of shear‐thinning bioinks with high printability and structural fidelity. The mechanical properties, swelling kinetics, and degradation rate of 3D printed constructs can be modulated by changing the ratio of PEG:PEGDTT and nanosilicates concentration. Due to high surface area and charged characteristic of nanosilicates, protein therapeutics can be sequestered in 3D printing structure for prolong duration. Sustained release of pro‐angiogenic therapeutics from 3D printed structure, promoted rapid migration of human endothelial umbilical vein cell. This approach to design biologically active inks to control and direct cell behavior can be used to engineer 3D complex tissue structure for regenerative medicine. 

Abstract 3D bioprinting is an emerging additive manufacturing technique to fabricate constructs for human disease modeling. However, current cell‐laden bioinks lack sufficient biocompatibility, printability, and structural stability needed to translate this technology to preclinical and clinical trials. Here, a new class of nanoengineered hydrogel‐based cell‐laden bioinks is introduced, that can be printed into 3D, anatomically accurate, multicellular blood vessels to recapitulate both the physical and chemical microenvironments of native human vasculature. A remarkably unique characteristic of this bioink is that regardless of cell density, it demonstrates a high printability and ability to protect encapsulated cells against high shear forces in the bioprinting process. 3D bioprinted cells maintain a healthy phenotype and remain viable for nearly one‐month post‐fabrication. Leveraging these properties, the nanoengineered bioink is printed into 3D cylindrical blood vessels, consisting of living co‐culture of endothelial cells and vascular smooth muscle cells, providing the opportunity to model vascular function and pathophysiology. Upon cytokine stimulation and blood perfusion, this 3D bioprinted vessel is able to recapitulate thromboinflammatory responses observed only in advanced in vitro preclinical models or in vivo. Therefore, this 3D bioprinted vessel provides a potential tool to understand vascular disease pathophysiology and assess therapeutics, toxins, or other chemicals. 

Abstract Clay nanomaterials are an emerging class of 2D biomaterials of interest due to their atomically thin layered structure, charged characteristics, and well‐defined composition. Synthetic nanoclays are plate‐like polyions composed of simple or complex salts of silicic acids with a heterogeneous charge distribution and patchy interactions. Due to their biocompatible characteristics, unique shape, high surface‐to‐volume ratio, and charge, nanoclays are investigated for various biomedical applications. Here, a critical overview of the physical, chemical, and physiological interactions of nanoclay with biological moieties, including cells, proteins, and polymers, is provided. The state‐of‐the‐art biomedical applications of 2D nanoclay in regenerative medicine, therapeutic delivery, and additive manufacturing are reviewed. In addition, recent developments that are shaping this emerging field are discussed and promising new research directions for 2D nanoclay‐based biomaterials are identified. 

Abstract Additive manufacturing is a promising method for producing customized 3D bioactive constructs for regenerative medicine. Here, 3D printed highly osteogenic scaffolds using nanoengineered ionic–covalent entanglement ink (NICE) for bone tissue engineering are reported. This NICE ink consists of ionic–covalent entanglement reinforced with Laponite, a 2D nanosilicate (nSi) clay, allowing for the printing of anatomic‐sized constructs with high accuracy. The 3D printed structure is able to maintain high structural stability in physiological conditions without any significant swelling or deswelling. The presence of nSi imparts osteoinductive characteristics to the NICE scaffolds, which is further augmented by depositing pluripotent stem cell‐derived extracellular matrix (ECM) on the scaffolds. This is achieved by stimulating human induced pluripotent stem cell‐derived mesenchymal stem cells (iP‐hMSCs) with 2‐chloro‐5‐nitrobenzanilide, a PPARγ inhibitor that enhances Wnt pathway, resulting in the deposition of an ECM characterized by high levels of collagens VI and XII found in anabolic bone. The osteoinductive characteristics of these bioconditioned NICE (bNICE) scaffolds is demonstrated through osteogenic differentiation of bone marrow derived human mesenchymal stem cells. A significant increase in the expression of osteogenic gene markers as well as mineralized ECM are observed on bioconditioned NICE (bNICE) scaffolds compared to bare scaffolds (NICE). The bioconditioned 3D printed scaffolds provide a unique strategy to design personalized bone grafts for in situ bone regeneration.