Editorial for the Special Issue "Hydrogels for 3D Printing".

Hydrogels, which are three-dimensional networks of hydrophilic polymers capable of absorbing and retaining large amounts of water, have emerged as versatile materials with vast potential in various fields [...].

Pellets and gummies: Seeking a 3D printed gastro-resistant omeprazole dosage for paediatric administration.

The production of 3D printed pharmaceuticals has thrived in recent years, as it allows the generation of customised medications in small batches. This is particularly helpful for patients who need specific doses or formulations, such as children. Compounding pharmacies seek alternatives to conventional solid oral doses, opting for oral liquid formulations. However, ensuring quality and stability, especially for pH-sensitive APIs like omeprazole, remains a challenge. This paper presents the application of semi-solid extrusion 3D printing technology to develop patient-tailored medicinal gummies, with an eye-catching appearances, serving as an innovative omeprazole pharmaceutical form for paediatric use. The study compares 3D printing hydrogels with dissolved omeprazole to hydrogels loaded with gastro-resistant omeprazole pellets, a ground-breaking approach.. Gastro-resistance and dissolution profiles were studied using different methods for better comparison and to emphasize the significance of the assay's methodology. Both developed formulas exhibit proper rheology, good printability, and meet content and mass uniformity standards. However, the high gastro-resistance and suitable release profile of 3D printed chewable semi-solid doses with enteric pellets highlight this as an effective strategy to address the challenge of paediatric medication.

Essential Guide to Hydrogel Rheology in Extrusion 3D Printing: How to Measure It and Why It Matters?

Rheology plays a crucial role in the field of extrusion-based three-dimensional (3D) printing, particularly in the context of hydrogels. Hydrogels have gained popularity in 3D printing due to their potential applications in tissue engineering, regenerative medicine, and drug delivery. The rheological properties of the printing material have a significant impact on its behaviour throughout the 3D printing process, including its extrudability, shape retention, and response to stress and strain. Thus, understanding the rheological characteristics of hydrogels, such as shear thinning behaviour, thixotropy, viscoelasticity, and gelling mechanisms, is essential for optimising the printing process and achieving desired product quality and accuracy. This review discusses the theoretical foundations of rheology, explores different types of fluid and their properties, and discusses the essential rheological tests necessary for characterising hydrogels. The paper emphasises the importance of terminology, concepts, and the correct interpretation of results in evaluating hydrogel formulations. By presenting a detailed understanding of rheology in the context of 3D printing, this review paper aims to assist researchers, engineers, and practitioners in the field of hydrogel-based 3D printing in optimizing their printing processes and achieving desired product outcomes.

3D Printable Dynamic Hydrogel: As Simple as it Gets!

3D printing technology offers a vast range of applications for tissue engineering applications. Over the past decade a vast range of new equipment has been developed; while, 3D printable biomaterials, especially hydrogels, are investigated to fit the printability requirements. The current candidates for bioprinting often require post-printing cross-linking to maintain their shape. On the other hand, dynamic hydrogels are considered as the most promising candidate for this application with their extrudability and self-healing properties. However, it proves to be very difficult to match the required rheological in a simple material. Here, this study presents for the first time the simplest formulation of a dynamic hydrogel based on thiol-functionalized hyaluronic acid formulated with gold ions that fulfill all the requirements to be printed without the use of external stimuli, as judged by the rheological studies. The printability is also demonstrated with a 3D printer allowing for the printing of the dynamic hydrogel as it is, achieving 3D construct with a relatively good precision and up to 24 layers, corresponding to 10 mm high. This material is the simplest 3D printable hydrogel and its mixture with cells and biological compounds is expected to open a new era in 3D bioprinting.

Effect on Rheological Properties and 3D Printability of Biphasic Calcium Phosphate Microporous Particles in Hydrocolloid-Based Hydrogels.

The production of patient-specific bone substitutes with an exact fit through 3D printing is emerging as an alternative to autologous bone grafting. To the success of tissue regeneration, the material characteristics such as porosity, stiffness, and surface topography have a strong influence on the cell-material interaction and require significant attention. Printing a soft hydrocolloid-based hydrogel reinforced with irregularly-shaped microporous biphasic calcium phosphate (BCP) particles (150-500 µm) is an alternative strategy for the acquisition of a complex network with good mechanical properties that could fulfill the needs of cell proliferation and regeneration. Three well-known hydrocolloids (sodium alginate, xanthan gum, and gelatin) have been combined with BCP particles to generate stable, homogenous, and printable solid dispersions. Through rheological assessment, it was determined that the crosslinking time, printing process parameters (infill density percentage and infill pattern), as well as BCP particle size and concentration all influence the stiffness of the printed matrices. Additionally, the swelling behavior on fresh and dehydrated 3D-printed structures was investigated, where it was observed that the BCP particle characteristics influenced the constructs' water absorption, particle diffusion out of the matrix and degradability.

Three-dimensional bioprinted cancer models: A powerful platform for investigating tunneling nanotube-like cell structures in complex microenvironments.

Bioprinting technology offers layer-by-layer positioning of cells within 3D space with complexity and a defined architecture. Cancer models based in this biofabrication technique are important tools to achieve representative and realistic in vivo conditions of the tumor microenvironment. Here, we show the development of a proof-of-concept three-dimensional bioprinted cancer model that successfully recapitulates the intercellular communication via the assembly of functional tunneling nanotube (TNT)-like cell projections. Different combinations of collagen-containing culture medium, sodium alginate and gelatin were initially prepared and rheologically evaluated. The optimized mixture was used to print two preliminary 3D models for cancer cell seeding. Favourable results in cell viability and proliferation led to the inclusion of 786-O renal cancer cells into the biomaterial mixture to directly bioprint the most suitable 3D model with embedded cells. Bioprinted cells remained viable for at least 15 days of culture and proliferated. More importantly, these cancer cells were able to build TNT-like cellular projections inside the hydrogel that established direct contacts between distant cells. We show that these structures were used as channels for the scrolling and intercellular transfer of mitochondria thus reproducing TNT's function in 2D culture systems. This 3D bioprinted renal cancer model provides a novel alternative tool for studying the functional relevance of TNT-like structures in tumorigenesis and anticancer drug susceptibility in a highly controlled and reproducible tumor microenvironment.

3D printed gummies: Personalized drug dosage in a safe and appealing way.

Obtention of customized dosage forms is one of the main attractions of 3D printing in pharmaceuticals. In this sense, children are one of the groups within the population with a greater need for drug doses adapted to their requirements (age, weight, pathological state…), but most 3D printed oral dosages are solid forms and, therefore, not suitable for them. This work developed patient-tailored medicinal gummies, an alternative oral dosage form with eye-catching appearance and appropriate organoleptic characteristics. Four inks were formulated, characterised and 3D printed by means of syringe-based extrusion mechanism. Different tests were performed to ensure reproducibility of the process and validate work methodology for dosage unit fabrication applying basic manufacturing standards. Rheological test helped in evaluating inks printability. Visual characterization concluded that drugmies, apart from a high fidelity in the 3D model shape reproduction, had a bright and uniformly coloured appearance and a pleasant aroma, which made them highly appetising and attractive. The printed gummy oral dosages complied comfortably with the mass uniformity assay regardless of the formulated ink used or the 3D model selected for printing. Ranitidine hydrochloride individual contents were determined using uv-vis spectrophotometry, showing successful results both in dose accuracy, uniformity of drug content and dissolution.