A thermoresponsive Pluronic/alginate semisynthetic hydrogel is used to bioprint 3D hepatic constructs, with the aim to investigate liver-specific metabolic activity of the 3D constructs compared to traditional 2D adherent cultures. The bioprinting method relies on a bioinert hydrogel and is characterized by high-shape fidelity, mild depositing conditions and easily controllable gelation mechanism. Furthermore, the dissolution of the sacrificial Pluronic templating agent significantly ameliorates the diffusive properties of the printed hydrogel. The present findings demonstrate high viability and liver-specific metabolic activity, as assessed by synthesis of urea, albumin, and expression levels of the detoxifying CYP1A2 enzyme of cells embedded in the 3D hydrogel system. A markedly increased sensitivity to a well-known hepatotoxic drug (acetaminophen) is observed for cells in 3D constructs compared to 2D cultures. Therefore, the 3D model developed herein may represent an in vitro alternative to animal models for investigating drug-induced hepatotoxicity.
- Keywords
- 3D liver models, Pluronic/alginate thermogels, bioprinting, drug hepatotoxicity, hepatic constructs,
- MeSH
- Printing, Three-Dimensional MeSH
- Bioprinting * MeSH
- Hydrogels MeSH
- Chemical and Drug Induced Liver Injury * MeSH
- Tissue Engineering MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Hydrogels MeSH
3D bioprinting is revolutionizing tissue engineering and regenerative medicine by enabling the precise fabrication of biologically functional constructs. At its core, the success of 3D bioprinting hinges on the development of bioinks, hydrogel-based materials that support cellular viability, proliferation, and differentiation. However, conventional bioinks face limitations in mechanical strength, biological activity, and customization. Recent advancements in genetic engineering have addressed these challenges by enhancing the properties of bioinks through genetic modifications. These innovations allow the integration of stimuli-responsive elements, bioactive molecules, and extracellular matrix (ECM) components, significantly improving the mechanical integrity, biocompatibility, and functional adaptability of bioinks. This review explores the state-of-the-art genetic approaches to bioink development, emphasizing microbial engineering, genetic functionalization, and the encapsulation of growth factors. It highlights the transformative potential of genetically modified bioinks in various applications, including bone and cartilage regeneration, cardiac and liver tissue engineering, neural tissue reconstruction, and vascularization. While these advances hold promise for personalized and adaptive therapeutic solutions, challenges in scalability, reproducibility, and integration with multi-material systems persist. By bridging genetics and bioprinting, this interdisciplinary field paves the way for sophisticated constructs and innovative therapies in tissue engineering and regenerative medicine.
- Keywords
- 3D bioprinting, Bioink, Gel, Genetics, Tissue engineering,
- MeSH
- Printing, Three-Dimensional * MeSH
- Biocompatible Materials * chemistry MeSH
- Bioprinting * methods MeSH
- Extracellular Matrix chemistry MeSH
- Hydrogels chemistry MeSH
- Ink * MeSH
- Humans MeSH
- Regenerative Medicine MeSH
- Tissue Engineering * methods MeSH
- Tissue Scaffolds MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Biocompatible Materials * MeSH
- Hydrogels MeSH
'Bioinks' are important tools for the fabrication of artificial living-tissue constructs that are able to mimic all properties of native tissues via 3D bioprinting technologies. Bioinks are most commonly made by incorporating live cells of interest within a natural or synthetic biocompatible polymeric matrix. In oncology research, the ability to recreate a tumor microenvironment (TME) using by 3D bioprinting constitutes a promising approach for drug development, screening, and in vitro cancer modeling. Here, we review the different types of bioink used for 3D bioprinting, with a focus on its application in cancer management. In addition, we consider the fabrication of bioink using customized materials/cells and their properties in the field of cancer drug discovery.
- MeSH
- Printing, Three-Dimensional * MeSH
- Bioprinting * MeSH
- Humans MeSH
- Neoplasms drug therapy MeSH
- Drug Discovery * MeSH
- Antineoplastic Agents therapeutic use MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Antineoplastic Agents MeSH
Reconstruction with the use of custom-made implants aims at optimal replacement of lost or damaged bone structures and restoration of their funkction. In this study the development and construction of a custom-made implant and the operative technique used for the treatment of an extensive tibial defect are described. The patient was a 65-year-old man treated for over 20 years for psoriatic arthritis and severe instability of the right knee, particularly in the frontal plane, with a worsening varus deformity. The radiogram showed an extensive destruction of the medial tibial condyle that also deeply involved the lateral condyle. The extent of defect made it impossible to use any commercial tibial augmentation. The geometry of the custom-designed implant for the medial tibial condyle was constructed on the basis of a 3D defect model and the shape of the medial tibial condyle of the collateral knee seen on CT scans. After its correct shape was verified on a plastic model, its coordinates were set in the software of a machine tool, and a titanium augmentation otherwise compatible with a standard knee replacement was produced.The use of such a custom implant to complete standard total knee arthroplasty has so far been demanding in terms of organisation and manufacture. Its production in the future could be facilitated by substituting titanium for plastic material such as poly-ether-ether-ketone (PEEK). Key words: custom-made implant, tibial augmentation, knee prosthesis.
- MeSH
- Computer-Aided Design * MeSH
- Humans MeSH
- Prosthesis Design * MeSH
- Prostheses and Implants * MeSH
- Arthritis, Psoriatic surgery MeSH
- Aged MeSH
- Tibia surgery MeSH
- Arthroplasty, Replacement, Knee * MeSH
- Imaging, Three-Dimensional MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- English Abstract MeSH
- Journal Article MeSH
- Case Reports MeSH
The development of bioink-based 3D-printed scaffolds has revolutionized bone tissue engineering (BTE) by enabling patient-specific and biomimetic constructs for bone regeneration. This review focuses on the biocompatibility and mechanical properties essential for scaffold performance, highlighting advancements in bioink formulations, material combinations, and printing techniques. The key biomaterials, including natural polymers (gelatin, collagen, alginate), synthetic polymers (polycaprolactone, polyethylene glycol), and bioactive ceramics (hydroxyapatite, calcium phosphate), are discussed concerning their osteoconductivity, printability, and structural integrity. Despite significant progress, challenges remain in achieving optimal mechanical strength, degradation rates, and cellular interactions. The review explores emerging strategies such as gene-activated bioinks, nanocomposite reinforcements, and crosslinking techniques to enhance scaffold durability and bioactivity. By synthesizing recent developments, this work provides insights into future directions for bioink-based scaffolds, paving the way for more effective and personalized bone regenerative therapies.
- MeSH
- Printing, Three-Dimensional * MeSH
- Biocompatible Materials * chemistry MeSH
- Bioprinting MeSH
- Ink MeSH
- Humans MeSH
- Bone Regeneration * MeSH
- Tissue Engineering methods MeSH
- Tissue Scaffolds * chemistry MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Biocompatible Materials * MeSH
Three-dimensional (3D) printing has showed great potential for the construction of electrochemical sensor devices. However, reported 3D-printed biosensors are usually constructed by physical adsorption and needed immobilizing reagents on the surface of functional materials. To construct the 3D-printed biosensors, the simple modification of the 3D-printed device by non-expert is mandatory to take advantage of the remote, distributed 3D printing manufacturing. Here, a 3D-printed electrode was prepared by fused deposition modeling (FDM) 3D printing technique and activated by chemical and electrochemical methods. A glucose oxidase-based 3D-printed nanocarbon electrode was prepared by covalent linkage method to an enzyme on the surface of the 3D-printed electrode to enable biosensing. X-ray photoelectron spectroscopy and scanning electron microscopy were used to characterize the glucose oxidase-based biosensor. Direct electrochemistry glucose oxidase-based biosensor with higher stability was then chosen to detect the two biomarkers, hydrogen peroxide and glucose by chronoamperometry. The prepared glucose oxidase-based biosensor was further used for the detection of glucose in samples of apple cider. The covalently linked glucose oxidase 3D-printed nanocarbon electrode as a biosensor showed excellent stability. This work can open new doors for the covalent modification of 3D-printed electrodes in other electrochemistry fields such as biosensors, energy, and biocatalysis.
- Keywords
- 3D-printed electrode, Covalent modification, Electrochemical detection, Glucose, Hydrogen peroxide,
- MeSH
- Printing, Three-Dimensional * MeSH
- Aspergillus niger enzymology MeSH
- Biosensing Techniques * methods MeSH
- Electrochemical Techniques * methods instrumentation MeSH
- Electrodes * MeSH
- Enzymes, Immobilized * chemistry metabolism MeSH
- Glucose * analysis chemistry MeSH
- Glucose Oxidase * chemistry metabolism MeSH
- Limit of Detection MeSH
- Malus chemistry MeSH
- Hydrogen Peroxide * chemistry analysis MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Enzymes, Immobilized * MeSH
- Glucose * MeSH
- Glucose Oxidase * MeSH
- Hydrogen Peroxide * MeSH
Engineered nanoparticles for the encapsulation of bioactive agents hold promise to improve disease diagnosis, prevention and therapy. To advance this field and enable clinical translation, the rational design of nanoparticles with controlled functionalities and a robust understanding of nanoparticle-cell interactions in the complex biological milieu are of paramount importance. Herein, a simple platform obtained through the nanocomplexation of glycogen nanoparticles and albumin is introduced for the delivery of chemotherapeutics in complex multicellular 2D and 3D systems. We found that the dendrimer-like structure of aminated glycogen nanoparticles is key to controlling the multivalent coordination and phase separation of albumin molecules to form stable glycogen-albumin nanocomplexes. The pH-responsive glycogen scaffold conferred the nanocomplexes the ability to undergo partial endosomal escape in tumour, stromal and immune cells while albumin enabled nanocomplexes to cross endothelial cells and carry therapeutic agents. Limited interactions of nanocomplexes with T cells, B cells and natural killer cells derived from human blood were observed. The nanocomplexes can accommodate chemotherapeutic drugs and release them in multicellular 2D and 3D constructs. The drugs loaded on the nanocomplexes retained their cytotoxic activity, which is comparable with the activity of the free drugs. Cancer cells were found to be more sensitive to the drugs in the presence of stromal and immune cells. Penetration and cytotoxicity of the drug-loaded nanocomplexes in tumour mimicking tissues were validated using a 3D multicellular-collagen construct in a perfusion bioreactor. The results highlight a simple and potentially scalable strategy for engineering nanocomplexes made entirely of biological macromolecules with potential use for drug delivery.
- MeSH
- Albumins * chemistry MeSH
- Endothelial Cells MeSH
- Glycogen * chemistry MeSH
- Humans MeSH
- Nanoparticles * chemistry MeSH
- Antineoplastic Agents * administration & dosage MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Albumins * MeSH
- Glycogen * MeSH
- Antineoplastic Agents * MeSH
Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel-like scaffolds and endothelial cells seeded in their lumen form native-like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites the bioprinted vasculature and endothelium to cooperatively create vessels, enabling tissue perfusion through the scaffold lumen. Using a cuffing microsurgery approach, the engineered tissue is directly anastomosed with a rat femoral artery, promoting a rich host vasculature within the implanted tissue. After two weeks in vivo, contrast microcomputer tomography imaging and lectin perfusion of explanted engineered tissues verify the host ingrowth vasculature's functionality. Furthermore, the hierarchical vessel network (VesselNet) supports in vitro functionality of cardiomyocytes. Finally, the proposed approach is expanded to mimic complex structures with native-like millimetric vessels. This work presents a novel strategy aiming to create fully-engineered patient-specific thick tissue flaps.
- Keywords
- 3D bioprinting, ECM bioink, engineered flap, personalized medicine, tissue engineering, vascularization,
- MeSH
- Printing, Three-Dimensional MeSH
- Femoral Artery surgery MeSH
- Biomimetic Materials chemistry MeSH
- Bioprinting methods MeSH
- Endothelial Cells cytology metabolism MeSH
- Hydrogels chemistry MeSH
- Ink MeSH
- Stem Cells cytology metabolism MeSH
- Collagen Type I chemistry genetics metabolism MeSH
- Rats MeSH
- Humans MeSH
- Methacrylates chemistry MeSH
- Polymers chemistry MeSH
- Rats, Sprague-Dawley MeSH
- Prostheses and Implants MeSH
- Tissue Engineering * MeSH
- Tissue Scaffolds chemistry MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Hydrogels MeSH
- Collagen Type I MeSH
- Methacrylates MeSH
- Polymers MeSH
In stereolithographic (SLA) 3D printing, objects are constructed by exposing layers of photocurable resin to UV light. It is a highly user-friendly fabrication method that opens a possibility for technology sharing through CAD file online libraries. Here, we present a prototyping procedure of a microfluidics-enhanced dot-blot device (Affiblot) designed for simple and inexpensive screening of affinity molecule characteristics (antibodies, oligonucleotides, cell receptors, etc.). The incorporation of microfluidic features makes sample processing user-friendly, less time-consuming, and less laborious, all performed completely on-device, distinguishing it from other dot-blot devices. Initially, the Affiblot device was fabricated using CNC machining, which required significant investment in manual post-processing and resulted in low reproducibility. Utilization of SLA 3D printing reduced the amount of manual post-processing, which significantly streamlined the prototyping process. Moreover, it enabled the fabrication of previously impossible features, including internal fluidic channels. While 3D printing of sub-millimeter microchannels usually requires custom-built printers, we were able to fabricate microfluidic features on a readily available commercial printer. Open microchannels in the size range 200-300 μm could be fabricated with reliable repeatability and sealed with a replaceable foil. Economic aspects of device fabrication are also discussed.
- Keywords
- 3D printing, Antibody, Dot-blot, Microfluidics, Prototyping,
- MeSH
- Printing, Three-Dimensional * MeSH
- Lab-On-A-Chip Devices MeSH
- Humans MeSH
- Microfluidic Analytical Techniques instrumentation methods MeSH
- Stereolithography * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The problem of designing tablet geometry and its internal structure that results into a specified release profile of the drug during dissolution was considered. A solution method based on parametric programming, inspired by CAD (computer-aided design) approaches currently used in other fields of engineering, was proposed and demonstrated. The solution of the forward problem using a parametric series of structural motifs was first carried out in order to generate a library of drug release profiles associated with each structural motif. The inverse problem was then solved in three steps: first, the combination of basic structural motifs whose superposition provides the closest approximation of the required drug release profile was found by a linear combination of pre-calculated release profiles. In the next step, the final tablet design was constructed and its dissolution curve found computationally. Finally, the proposed design was 3D printed and its dissolution profile was confirmed experimentally. The computational method was based on the numerical solution of drug diffusion in a boundary layer surrounding the tablet, coupled with erosion of the tablet structure encoded by the phase volume function. The tablets were 3D printed by fused deposition modelling (FDM) from filaments produced by hot-melt extrusion. It was found that the drug release profile could be effectively controlled by modifying the tablet porosity. Custom release profiles were obtained by combining multiple porosity regions in the same tablet. The computational method yielded accurate predictions of the drug release rate for both single- and multi-porosity tablets.
- Keywords
- 3D printing, dissolution, hot-melt extrusion, mathematical modelling, parametric programming,
- MeSH
- Printing, Three-Dimensional * MeSH
- Technology, Pharmaceutical methods MeSH
- Porosity MeSH
- Tablets chemistry pharmacokinetics MeSH
- Drug Liberation MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Tablets MeSH