Preparation and Characterisation of Cellulose Nanocrystal/Alginate/Polyethylene Glycol Diacrylate (CNC/Alg/PEGDA) Hydrogel Using Double Network Crosslinking Technique for Bioprinting Application

In this study, we aimed to prepare and characterise hydrogel formulations using cellulose nanocrystals (CNCs), alginate (Alg), and polyethylene glycol diacrylate (PEGDA). The CNC/Alg/PEGDA formulations were formed using a double network crosslinking approach. Firstly, CNC was extracted from oil palm trunk, and the size and morphology of the CNCs were characterised using TEM analysis. Secondly, different formulations were prepared using CNCs, Alg, and PEGDA. The mixtures were crosslinked with Ca2+ ions and manually extruded using a syringe before being subjected to UV irradiation at 365 nm. The shear-thinning properties of the formulations were tested prior to any crosslinking, while the determination of storage and loss modulus was conducted post extrusion after the Ca2+ ion crosslink using a rheometer. For the analysis of swelling behaviour, the constructs treated with UV were immersed in PBS solution (pH 7.4) for 48 h. The morphology of the UV crosslinked construct was analysed using SEM imaging. The extracted CNC exhibited rod-like structures with an average diameter and length of around 7 ± 2.4 and 113 ± 20.7 nm, respectively. Almost all CNC/Alg/PEGDA formulations (pre-gel formulation) displayed shear-thinning behaviour with the power-law index η < 1, and the behaviour was more prominent in the 1% [w/v] Alg formulations. The CNC/Alg/PEGDA with 2.5% and 4% [w/v] Alg displayed a storage modulus dominance over loss modulus (G′ > G″) which suggests good shape fidelity. After the hydrogel constructs were subjected to UV treatment at 365 nm, only the F8 construct [4% CNC: 4% Alg: 40% PEGDA] demonstrated tough and flexible characteristics that possibly mimic the native articular cartilage property due to a similar water content percentage (79.5%). In addition, the small swelling ratio of 4.877 might contribute to a minimal change of the 3D construct’s geometry. The hydrogel revealed a rough and wavy surface, and the pore size ranged from 3 to 20 µm. Overall, the presence of CNCs in the double network hydrogel demonstrated importance and showed positive effects towards the fabrication of a potentially ideal 3D bioprinted scaffold.

Evaluation of Polycaprolactone Electrospun Nanofiber-Composites for Artificial Skin Based on Dermal Fibroblast Culture

The study’s aim was to develop a dermal equivalent scaffold that can mimic the architecture and biological performance of the human dermis. Poly ε-caprolactone (PCL) electrospun nanofiber material (ENF) was assembled with polyethylene glycol diacrylate (PEGDA), sodium alginate (SA) and type I collagen (CG1) to develop three groups of dermal equivalent scaffolds. These scaffolds were named PEGDA-PCL, SA-PCL and CG1-PCL. Scanning electron microscopy (SEM) images of cell-free scaffolds’ top and cross-sectional surface were collected and analyzed to examine internal morphology, specifically the adhesiveness of PCL fibers with the different scaffolds. Human dermal fibroblasts were cultured on each of the scaffolds. Cell viability studies including cell adhesion, cell differentiation and stress fiber production were conducted on each scaffold. Furthermore, the architectural integrity of each scaffold was verified by degradation analysis for 2 weeks by soaking each scaffold in phosphate-buffered saline (PBS) solution. Finally, we conducted rheological characteristics of each scaffold. Based on our results from the above analysis, the study concluded that CG1-PCL is best suitable for the dermal equivalent model and has potential to be used as a graft for skin repair.

Bioprinting the Tumor Microenvironment with an Upgraded Consumer Stereolithographic 3D Printer

A widespread application of three-dimensional (3D) bioprinting in basic and translational research requires the accessibility to affordable printers able to produce physiologically relevant tissue models. To facilitate the use of bioprinting as a standard technique in biology, an open-source device based on a consumer-grade 3D stereolithographic (SL) printer was developed. This SL bioprinter can produce complex constructs that preserve cell viability and recapitulate the physiology of tissues. The detailed documentation of the modifications apported to the printer as well as a throughout performance analysis allow for a straightforward adoption of the device in other labs and its customization for specific applications. Given the low cost, several modified bioprinters could be simultaneously operated for a highly parallelized tissue production. To showcase the capability of the bioprinter, we produced constructs consisting of patient-derived cholangiocarcinoma organoids encapsulated in a gelatin methacrylate (GelMA)/polyethylene glycol diacrylate (PEGDA) hydrogel. A thorough characterization of different GelMA/PEGDA ratios revealed that the mechanical properties of the bioprinted tumor model can be accurately fine-tuned to mimic a specific tumor micro-environment. Immunofluorescence and gene expression analyses of tumor markers confirmed that the bioprinted synthetic hydrogel provides a flexible and adequate replacement of animal-derived reconstituted extracellular matrix.

3D Printing Polymeric Materials for Robots with Embedded Systems

The fabrication of robots and their embedded systems is challenging due to the complexity of the interacting components. The integration of additive manufacturing (AM) to robotics has made advancements in robotics manufacturing through sophisticated and state-of-the-art AM technologies and materials. With the emergence of 3D printing, 3D printing materials are also being considered and engineered for specific applications. This study reviews different 3D printing materials for 3D printing embedded robotics. Materials such as polyethylene glycol diacrylate (PEGDA), acrylonitrile butadiene styrene (ABS), flexible photopolymers, silicone, and elastomer-based materials were found to be the most used 3D printing materials due to their suitability for robotic applications. This review paper revealed that the key areas requiring more research are material formulations for improved mechanical properties, cost, and the inclusion of materials for specific applications. Future perspectives are also provided.

3D printing nanocomposite hydrogels with lattice vascular networks using stereolithography

Hydrogels have emerged as leading candidates to reproduce native extracellular matrix. To provide structures and functions similar to tissues in vivo, controlled porosity and vascular networks are required. However, fabrication techniques to introduce these are still limited. In this study we propose stereolithography as a fabrication technique to achieve 3D vascular networks using water-based solvents only. A 3D printable hydrogel is formulated based on available commercial chemicals such as acrylamide (AAm) and polyethylene glycol diacrylate 700 (PEGDA700), with nanocellulose crystals (CNC) as a nanofiller. An optimisation procedure to increase resolution, tune porosity as well as mechanical properties is developed. The results highlight the importance of photoabsorber addition to improve channel resolution. We demonstrate that with the adequate choice of chemicals and fillers for photocurable formulations, structural and functional properties of the fabricated scaffold can be tailored, opening the path for advanced applications. Graphic abstract

Hydrophilic Excipient-Independent Drug Release from SLA-Printed Pellets

Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger–Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone.

Polyethylene glycol diacrylate scaffold filled with cell-laden methacrylamide gelatin/alginate hydrogels used for cartilage repair

Natural cartilage tissue has excellent mechanical properties and has certain cellular components. At this stage, it is a great challenge to produce cartilage scaffolds with excellent mechanical properties, biocompatibility, and biodegradability. Hydrogels are commonly used in tissue engineering because of their excellent biocompatibility; however, the mechanical properties of commonly used hydrogels are difficult to meet the requirements of making cartilage scaffolds. The mechanical properties of high concentration polyethylene glycol diacrylate (PEGDA) hydrogel are similar to those of natural cartilage, but its biocompatibility is poor. Low concentration hydrogel has better biocompatibility, but its mechanical properties are poor. In this study, two different hydrogels were combined to produce cartilage scaffolds with good mechanical properties and strong biocompatibility. First, the PEGDA grid scaffold was printed with light curing 3D printing technology, and then the low concentration GelMA/Alginate hydrogel with chondral cells was filled into the PEGDA grid scaffold. After a series of cell experiments, the filling hydrogel with the best biocompatibility was screened out, and finally the filled hydrogel with cells and excellent biocompatibility was obtained. Cartilage tissue engineering scaffolds with certain mechanical properties were found to have a tendency of cartilage formation in in vitro culture. Compared with the scaffold obtained by using a single hydrogel, this molding method can produce a tissue engineering scaffold with excellent mechanical properties on the premise of ensuring biocompatibility, which has a certain potential application value in the field of cartilage tissue engineering.

Novel reusable hydrogel adsorbents for precious metal recycle

A novel polyethylene glycol diacrylate-allylthiourea (ATU-PEGDA) hydrogel was simply synthesized through photo-reaction. Modified thiourea simultaneously employed chelation and electrostatic force to selectively recycle Ag(I) and Pd(II) from electrolytic wastewater. Sorption efficiency was nearly 100% for Ag(I) and Pd(II), which occurred at initial pH of 1 within 300 min. The adsorption characteristics of ATU-PEGDA followed Langmuir isotherm model and the maximum adsorption capacity of Ag(I) and Pd(II) achieved 83.33 and 152.81 mg g−1 sorbent, respectively where Pseudo-first order model demonstrate the adsorption kinetics. In the presence of other heavy metals, ATU-PEGDA performed high selectivity, 0.89 and 1.31 towards Ag(I) and Pd(II). ATU-PEGDA can be completely regenerated within 120 min using 0.5 M thiourea—0.001 M HNO3 and 1 M thiourea—4 M HCl after the adsorption of Ag(I) and Pd(II), respectively. Thiourea-branched structure was created after regeneration, improving the adsorption capacity. Compared to initial hydrogel, the adsorption capacity of Ag(I) and Pd(II) increased 31.83 ± 3.08% and 75.12 ± 11.02%, respectively. Over 10 consecutive adsorption–desorption cycles, ATU-PEGDA performed 111.34 and 263.79 mg g−1 sorbent in adsorption capacity of Ag(I) and Pd(II). Chromism of ATU-PEGDA hydrogel was a benefit to determine adsorption saturation and completely desorption of Ag(I) and Pd(II). Potentially, ATU-PEGDA can be extended to industrial applications.

Evaluation of Microfluidic Approaches to Encapsulate Cells into PEGDA Microparticles

Purpose Polyethylene glycol diacrylate (PEGDA) is increasingly used to microencapsulate cells via a vortex-induced water-in-oil emulsion process. Herein, we evaluated methods to encapsulate cells into microparticles using microfluidic methods. Methods PEGDA prepolymer solution with or without cells was photopolymerized with white light under varying microfluidic parameters to form empty microspheres or cell-laden microparticles. Microparticles and entrapped cells were assessed for size and viability. Results PEGDA microparticles were easily formed when cells were absent; the introduction of cells resulted in aggregation that clogged microfluidic devices, resulting in a mix of empty polymer microparticles and cells that were not encapsulated. Cells that were successfully encapsulated had poor viability. Conclusion Microfluidic methods may work for low density microencapsulation of mammalian cells; however, when the cell density within each microparticle must be relatively high, emulsion-based methods are superior to microfluidic methods. Lay Summary The synthetic polymer polyethylene glycol diacrylate (PEGDA) has been increasingly used to encapsulate cells into micrometer-sized hydrogel spheres (microspheres). One method to microencapsulate cells has been to form a water-in-oil emulsion with liquid polymer containing cells and then expose the suspended droplets to white light, polymerizing them into PEGDA hydrogel microspheres. Although successful, this method has poor control over the process, resulting in polydisperse microsphere sizes with varying cell density. We evaluated microfluidic methods to form both empty and cell-laden PEGDA microspheres. Although microfluidic methods resulted in monodisperse microsphere sizes, the introduction of cells resulted in clogging of microfluidic devices, non-spherical microparticles, and poor cell viability. Future Work Because the microfluidic approach successfully formed cell-free microspheres, the effect of reducing cell aggregation will be examined. Specifically, the use of anti-aggregation agents as well as a reduced cell density in the liquid polymer phase and their effects on polymer formation will be explored.