Highly conductive, stretchable, and biocompatible graphene oxide biocomposite hydrogel for advanced tissue engineering.

The importance of hydrogels in tissue engineering cannot be overemphasized due to their resemblance to the native extracellular matrix (ECM). However, natural hydrogels with satisfactory biocompatibility exhibit poor mechanical behavior, which hampers their application in stress-bearing soft tissue engineering. Here, we describe the fabrication of a double methacrylated gelatin bioink covalently linked to graphene oxide (GO) via a zero-length crosslinker, digitally light-processed (DLP) printable into 3D complex structures with high fidelity. The resultant natural hydrogel (GelGOMA) exhibits a conductivity of 15.0 S m-1 as a result of the delocalization of the π-orbital from the covalently linked GO. Furthermore, the hydrogel shows a compressive strength of 1.6 MPa, and a 2.0 mm thick GelGOMA can withstand a 1.0 kg ms­1 momentum. The printability and mechanical properties of GelGOMA were demonstrated by printing a fish heart with a functional fluid pumping mechanism and tricuspid valves. Its biocompatibility, electroconductivity, and physiological relevance enhanced the proliferation and differentiation of myoblasts and neuroblasts and the contraction of hiPSC-derived cardiomyocytes. GelGOMA demonstrates the potential for the tissue engineering of functional hearts and wearable electronic devices. .

Efficient Light-Based Bioprinting via Rutin Nanoparticle Photoinhibitor for Advanced Biomedical Applications.

Digital light processing (DLP) bioprinting, known for its high resolution and speed, enables the precise spatial arrangement of biomaterials and has become integral to advancing tissue engineering and regenerative medicine. Nevertheless, inherent light scattering presents significant challenges to the fidelity of the manufactured structures. Herein, we introduce a photoinhibition strategy based on Rutin nanoparticles (Rnps), attenuating the scattering effect through concurrent photoabsorption and free radical reaction. Compared to the widely utilized biocompatible photoabsorber tartrazine (Tar), Rnps-infused bioink enhanced printing speed (1.9×), interlayer homogeneity (58% less overexposure), resolution (38.3% improvement), and print tolerance (3× high-precision range) to minimize trial-and-error. The biocompatible and antioxidative Rnps significantly improved cytocompatibility and exhibited resistance to oxidative stress-induced damage in printed constructs, as demonstrated with human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs). The related properties of Rnps facilitate the facile fabrication of multimaterial, heterogeneous, and cell-laden biomimetic constructs with intricate structures. The developed photoinhibitor, with its profound adaptability, promises wide biomedical applications tailored to specific biological requirements.

Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers.

BACKGROUND: The encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy resistance cell states. Here, we deploy time series measurements of triple negative breast cancer (TNBC) single-cell transcriptomes, along with co-measured single-cell CN fitness, identifying genomic and transcriptomic mechanisms in drug-associated transcriptional cell states. RESULTS: We present scRNA-seq data (53,641 filtered cells) from serial passaging TNBC patient-derived xenograft (PDX) experiments spanning 2.5 years, matched with genomic single-cell CN data from the same samples. Our findings reveal distinct clonal responses within TNBC tumors exposed to platinum. Clones with high drug fitness undergo clonal sweeps and show subtle transcriptional reversion, while those with weak fitness exhibit dynamic transcription upon drug withdrawal. Pathway analysis highlights convergence on epithelial-mesenchymal transition and cytokine signaling, associated with resistance. Furthermore, pseudotime analysis demonstrates hysteresis in transcriptional reversion, indicating generation of new intermediate transcriptional states upon platinum exposure. CONCLUSIONS: Within a polyclonal tumor, clones with strong genotype-associated fitness under platinum remained fixed, minimizing transcriptional reversion upon drug withdrawal. Conversely, clones with weaker fitness display non-genomic transcriptional plasticity. This suggests CN-associated and CN-independent transcriptional states could both contribute to platinum resistance. The dominance of genomic or non-genomic mechanisms within polyclonal tumors has implications for drug sensitivity, restoration, and re-treatment strategies.

Engineering biomimetic silk fibroin hydrogel scaffolds with "organic-inorganic assembly" strategy for rapid bone regeneration.

Although natural polymers have been widely used in constructing bone scaffolds, it still remains challenging to fabricate natural polymer-derived bone scaffolds with biomimetic mechanical properties as well as outstanding osteogenic properties for large-size and weight-bearing bone defects regeneration. Herein, an "organic-inorganic assembly" strategy is developed to construct silk fibroin (SF)-based bone scaffolds with the aforementioned merits. After secondary structure reshuffling, the 3.3-fold increment of ß-sheet structures in SF hydrogel resulted in a 100-fold improvement of mineral-assembly efficacy via influencing the ion adsorption process and providing templates for mineral growth. Notably, abundant minerals were deposited within the hydrogel and also on the surface, which indicated entire mineral-assembly, which ensured the biomimetic mechanical properties of the digital light processing 3D printed SF hydrogel scaffolds with haversian-mimicking structure. In vitro experiments proved that the assembly between the mineral and SF results in rapid adhesion and enhanced osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. In vivo experiments further proved that the mineral-assembled SF hydrogel scaffold could significantly enhance integration and bone regeneration at the weight-bearing site within one month. This SF-based "organic-inorganic assembly" strategy sheds light on constructing cell-free, growth factor-free and natural polymer-derived bone scaffolds with biomimetic 3D structure, mechanical properties and excellent osteogenic properties.

Excess Dally-like Induces Malformation of Drosophila Legs.

Glypicans are closely associated with organ development and tumorigenesis in animals. Dally-like (Dlp), a membrane-bound glypican, plays pivotal roles in various biological processes in Drosophila. In this study, we observed that an excess of Dlp led to the malformation of legs, particularly affecting the distal part. Accordingly, the leg disc was shrunken and frequently exhibited aberrant morphology. In addition, elevated Dlp levels induced ectopic cell death with no apparent cell proliferation changes. Furthermore, Dlp overexpression in the posterior compartment significantly altered Wingless (Wg) distribution. We observed a marked expansion of Wg distribution within the posterior compartment, accompanied by a corresponding decrease in the anterior compartment. It appears that excess Dlp guides Wg to diffuse to cells with higher Dlp levels. In addition, the distal-less (dll) gene, which is crucial for leg patterning, was up-regulated significantly. Notably, dachshund (dac) and homothorax (hth) expression, also essential for leg patterning and development, only appeared to be negligibly affected. Based on these findings, we speculate that excess Dlp may contribute to malformations of the distal leg region of Drosophila, possibly through its influence on Wg distribution, dll expression and induced cell death. Our research advances the understanding of Dlp function in Drosophila leg development.

3D Printed Drug Delivery Systems in Action-Magnetic Resonance Imaging and Relaxometry for Monitoring Mass Transport Phenomena.

The hypothesis of the study was that (1) 3D printed drug delivery systems (DDS) could be characterized in situ during drug release using NMR/MRI techniques in terms of mass transport phenomena description (interfacial phenomena), particularly for systems dealing with two mobile phases (e.g., water and low molecular weight liquid polymer); (2) consequently, it could be possible to deduce how these interfacial mass transport phenomena influence functional properties of 3D printed DDS. Matrix drug delivery systems, prepared using masked stereolithography (MSLA), containing poly(ethylene glycol) diacrylate (PEGDA) and low molecular weight polyethylene glycol (PEG) with ropinirole hydrochloride (RH) were studied as example formulations. The PEGDA to PEG (mobile phase) concentration ratio influenced drug release. It was reflected in spatiotemporal changes in parametric T2 relaxation time (T2) and amplitude (A) images obtained using magnetic resonance imaging (MRI) and T1-T2 relaxation time correlations obtained using low-field time-domain nuclear magnetic resonance (LF TD NMR) relaxometry during incubation in water. For most of the tested formulations, two signal components related to PEG and water were assessed in the hydrated matrices by MRI relaxometry (parametric T2/A images). The PEG component faded out due to outward PEG diffusion and was gradually replaced by the water component. Both components spatially and temporally changed their parameters, reflecting evolving water-polymer interactions. The study shows that dynamic phenomena related to bidirectional mass transport can be quantified in situ using NMR and MRI techniques to gain insight into drug release mechanisms from 3D printed DDS systems.

Evaluation of Shear Bond Strengths of 3D Printed Materials for Permanent Restorations with Different Surface Treatments.

The development of high-filled 3D printing resin necessitates a bonding protocol for dental indirect restorations to achieve optimal bond strength after cementation. This study evaluates shear bond strengths of high-filler 3D printed materials for permanent restorations with various surface treatments. Rodin Sculpture 1.0 (50% lithium disilicate fillers) and 2.0 Ceramic Nanohybrid (>60% zirconia and lithium disilicate fillers) were tested, with Aelite All-Purpose Body composite resin as control. Samples were prepared, post-cured, and sandblasted with alumina (25 µm). Surface roughness was analyzed using an optical profilometer. Two bonding protocols were compared. First, groups were treated with lithium disilicate silane (Porcelain Primer) or zirconia primer (Z-Prime Plus) or left untreated without a bonding agent. Beam-shaped resin cement (DuoLink Universal) specimens were bonded and stored in a 37 °C water bath. Second, additional sets of materials were coated with a bonding agent (All-Bond Universal), either followed by silane application or left untreated. These sets were then similarly stored alongside resin cement specimens. Shear bond tests were performed after 24 h. SEM images were taken after debonding. One-Way ANOVA and post hoc Duncan were performed for the statistical analysis. Rodin 1.0 exhibited increased adhesive failure with silane or zirconia primer coating, but significantly improved bond strengths with bonding agent application. Rodin 2.0 showed consistent bond strengths regardless of bonding agent application, but cohesive failure rates increased with bonding agent and filler coating. In all groups, except for Rodin 1.0 without bonding agent, silane coating increased cohesive failure rate. In conclusion, optimal shear bond strength for high-filler 3D printing materials can be achieved with silane coating and bonding agent application.

Structural tuning of anisotropic mechanical properties in 3D-Printed hydrogel lattices.

We investigated the ability to tune the anisotropic mechanical properties of 3D-printed hydrogel lattices by modifying their geometry (lattice strut diameter, unit cell size, and unit cell scaling factor). Many soft tissues are anisotropic and the ability to mimic natural anisotropy would be valuable for developing tissue-surrogate "phantoms" for elasticity imaging (shear wave elastography or magnetic resonance elastography). Vintile lattices were 3D-printed in polyethylene glycol di-acrylate (PEGDA) using digital light projection printing. Two mechanical benchtop tests, dynamic shear testing and unconfined compression, were used to measure the apparent shear storage moduli (G') and apparent Young's moduli (E) of lattice samples. Increasing the unit cell size from 1.25 mm to 2.00 mm reduced the Young's and shear moduli of the lattices by 91% and 85%, respectively. Decreasing the strut diameter from 300 µm to 200 µm reduced the apparent shear moduli of the lattices by 95%. Increasing the geometric scaling ratio of the lattice unit cells from 1.00 × to 2.00 × increased mechanical anisotropy in shear (by a factor of 3.1) and in compression (by a factor of 2.9). Both simulations and experiments show that the effects of unit cell size and strut diameter are consistent with power law relationships between volume fraction and apparent elastic moduli. In particular, experimental measurements of apparent Young's moduli agree well with predictions of the theoretical Gibson-Ashby model. Thus, the anisotropic mechanical properties of a lattice can be tuned by the unit cell size, the strut diameter, and scaling factors. This approach will be valuable in designing tissue-mimicking hydrogel lattice-based composite materials for elastography phantoms and tissue engineered scaffolds.

Tailorable acrylate-endcapped urethane-based polymers for precision in digital light processing: Versatile solutions for biomedical applications.

Bioengineering seeks to replicate biological tissues exploiting scaffolds often based on polymeric biomaterials. Digital light processing (DLP) has emerged as a potent technique to fabricate tissue engineering (TE) scaffolds. However, the scarcity of suitable biomaterials with desired physico-chemical properties along with processing capabilities limits DLP's potential. Herein, we introduce acrylate-endcapped urethane-based polymers (AUPs) for precise physico-chemical tuning while ensuring optimal computer-aided design/computer-aided manufacturing (CAD/CAM) mimicry. Varying the polymer backbone (i.e. poly(ethylene glycol) (PEG) versus poly(propylene glycol) (PPG)) and photo-crosslinkable endcap (i.e. di-acrylate versus hexa-acrylate), we synthesized a series of photo-crosslinkable materials labeled as UPEG2, UPEG6, UPPG2 and UPPG6. Comprehensive material characterization including physico-chemical and biological evaluations, was followed by a DLP processing parametric study for each material. The impact of the number of acrylate groups per polymer (2 to 6) on the physico-chemical properties was pronounced, as reflected by a reduced swelling, lower water contact angles, accelerated crosslinking kinetics, and increased Young's moduli upon increasing the acrylate content. Furthermore, the different polymer backbones also exerted a substantial effect on the properties, including the absence of crystallinity, remarkably reduced swelling behaviors, a slight reduction in Young's modulus, and slower crosslinking kinetics for UPPG vs UPEG. The mechanical characteristics of DLP-printed samples showcased the ability to tailor the materials' stiffness (ranging from 0.4 to 5.3 MPa) by varying endcap chemistry and/or backbone. The in vitro cell assays confirmed biocompatibility of the material as such and the DLP-printed discs. Furthermore, the structural integrity of 3D scaffolds was preserved both in dry and swollen state. By adjusting the backbone chemistry or acrylate content, the post-swelling dimensions could be customized towards the targeted application. This study showcases the potential of these materials offering tailorable properties to serve many biomedical applications such as cartilage TE.

Three-Dimensional Bioprinted Skin Microrelief and Its Role in Skin Aging.

Skin aging is a complex physiological process, in which cells and the extracellular matrix (ECM) interreact, which leads to a change in the mechanical properties of skin, which in turn affects the cell secretion and ECM deposition. The natural skin microrelief that exists from birth has rarely been taken into account when evaluating skin aging, apart from the common knowledge that microreliefs might serve as the starting point or initialize micro-wrinkles. In fact, microrelief itself also changes with aging. Does the microrelief have other, better uses? In this paper, owing to the fast-developing 3D printing technology, skin wrinkles with microrelief of different age groups were successfully manufactured using the Digital light processing (DLP) technology. The mechanical properties of skin samples with and without microrelief were tested. It was found that microrelief has a big impact on the elastic modulus of skin samples. In order to explore the role of microrelief in skin aging, the wrinkle formation was numerically analyzed. The microrelief models of different age groups were created using the modified Voronoi algorithm for the first time, which offers fast and flexible mesh formation. We found that skin microrelief plays an important role in regulating the modulus of the epidermis, which is the dominant factor in wrinkle formation. The wrinkle length and depth were also analyzed numerically for the first time, owing to the additional dimension offered by microrelief. The results showed that wrinkles are mainly caused by the modulus change of the epidermis in the aging process, and compared with the dermis, the hypodermis is irrelevant to wrinkling. Hereby, we developed a hypothesis that microrelief makes the skin adaptive to the mechanical property changes from aging by adjusting its shape and size. The native-like skin samples with microrelief might shed a light on the mechanism of wrinkling and also help with understanding the complex physiological processes associated with human skin.

The Effect of Build Angle and Artificial Aging on the Accuracy of SLA- and DLP-Printed Occlusal Devices.

The aim of this study is to investigate the influence of printing material, build angle, and artificial aging on the accuracy of SLA- and DLP-printed occlusal devices in comparison to each other and to subtractively manufactured devices. A total of 192 occlusal devices were manufactured by one SLA-printing and two DLP-printing methods in 5 different build angles as well as milling. The specimens were scanned and superimposed to their initial CAD data and each other to obtain trueness and precision data values. A second series of scans were performed after the specimens underwent an artificial aging simulation by thermocycling. Again, trueness and precision were investigated, and pre- and post-aging values were compared. A statistically significant influence was found for all main effects: manufacturing method, build angle, and thermocycling, confirmed by two-way ANOVA. Regarding trueness, overall tendency indicated that subtractively manufactured splints were more accurate than the 3D-printed, with mean deviation values around ±0.15 mm, followed by the DLP1 group, with ±0.25 mm at 0 degree build angle. Within the additive manufacturing methods, DLP splints had significantly higher trueness for all build angles compared to SLA, which had the highest mean deviation values, with ±0.32 mm being the truest to the original CAD file. Regarding precision, subtractive manufacturing showed better accuracy than additive manufacturing. The artificial aging demonstrated a significant influence on the dimensional accuracy of only SLA-printed splints.

DLP 3D Printing of Levoglucosenone-Based Monomers: Exploiting Thiol-ene Chemistry for Bio-Based Polymeric Resins.

Additive manufacturing (AM) is a well-established technique that allows for the development of complex geometries and structures with multiple applications. While considered a more environmentally-friendly method than traditional manufacturing, a significant challenge lies in the availability and ease of synthesis of bio-based alternative resins. In our endeavor to valorize biomass, this work proposes the synthesis of new α,ω-dienes derived from cellulose-derived levoglucosenone (LGO). These dienes are not only straightforward to synthesize but also offer a tunable synthesis approach. Specifically, LGO is first converted into diol precursor, which is subsequently esterified using various carboxylic acids (in this case, 3-butenoic, and 4-pentenoic acids) through a straightforward chemical pathway. The resulting monomers were then employed in UV-activated thiol-ene chemistry for digital light process (DLP). A comprehensive study of the UV-curing process was carried out by Design of Experiment (DoE) to evaluate the influence of light intensity and photoinitiator to find the optimal curing conditions. Subsequently, a thorough thermo-mechanical characterization highlighted the influence of the chemical structure on material properties. 3D printing was performed, enabling the fabrication of complex and self-stain structures with remarkable accuracy and precision. Lastly, a chemical degradation study revealed the potential for end-of-use recycling of the bio-based thermosets.

Droplet bioprinting of acellular and cell-laden structures at high-resolutions.

Advances in digital light projection(DLP) based (bio) printers have made printing of intricate structures at high resolution possible using a wide range of photosensitive bioinks. A typical setup of a DLP bioprinter includes a vat or reservoir filled with liquid bioink, which presents challenges in terms of cost associated with bioink synthesis, high waste, and gravity-induced cell settling, contaminations, or variation in bioink viscosity during the printing process. Here, we report a vat-free, low-volume, waste-free droplet bioprinting method capable of rapidly printing 3D soft structures at high resolution using model bioinks and model cells. A multiphase many-body dissipative particle dynamics model was developed to simulate the dynamic process of droplet-based DLP printing and elucidate the roles of surface wettability and bioink viscosity. Process variables such as light intensity, photo-initiator concentration, and bioink formulations were optimized to print 3D soft structures (∼0.4-3 kPa) with a typical layer thickness of 50µm, an XY resolution of 38 ± 1.5µm and Z resolution of 237 ± 5.4µm. To demonstrate its versatility, droplet bioprinting was used to print a range of acellular 3D structures such as a lattice cube, a Mayan pyramid, a heart-shaped structure, and a microfluidic chip with endothelialized channels. Droplet bioprinting, performed using model C3H/10T1/2 cells, exhibited high viability (90%) and cell spreading. Additionally, microfluidic devices with internal channel networks lined with endothelial cells showed robust monolayer formation while osteoblast-laden constructs showed mineral deposition upon osteogenic induction. Overall, droplet bioprinting could be a low-cost, no-waste, easy-to-use, method to make customized bioprinted constructs for a range of biomedical applications.

Optimizing CT Abdomen-Pelvis Scan Radiation Dose: Examining the Role of Body Metrics (Waist Circumference, Hip Circumference, Abdominal Fat, and Body Mass Index) in Dose Efficiency.

Objective: This study investigates the correlation between patient body metrics and radiation dose in abdominopelvic CT scans, aiming to identify significant predictors of radiation exposure. Methods: Employing a cross-sectional analysis of patient data, including BMI, abdominal fat, waist, abdomen, and hip circumference, we analyzed their relationship with the following dose metrics: the CTDIvol, DLP, and SSDE. Results: Results from the analysis of various body measurements revealed that BMI, abdominal fat, and waist circumference are strongly correlated with increased radiation doses. Notably, the SSDE, as a more patient-centric dose metric, showed significant positive correlations, especially with waist circumference, suggesting its potential as a key predictor for optimizing radiation doses. Conclusions: The findings suggest that incorporating patient-specific body metrics into CT dosimetry could enhance personalized care and radiation safety. Conclusively, this study highlights the necessity for tailored imaging protocols based on individual body metrics to optimize radiation exposure, encouraging further research into predictive models and the integration of these metrics into clinical practice for improved patient management.

Fabrication of High Thermal Conductivity Aluminum Nitride Ceramics via Digital Light Processing 3D Printing.

The sintering of high-performance ceramics with complex shapes at low temperatures has a significant impact on the future application of ceramics. A joint process of digital light processing (DLP) 3D printing technology and a nitrogen-gas pressure-assisted sintering method were proposed to fabricate AlN ceramics in the present work. Printing parameters, including exposure energy and time, were optimized for the shaping of green bodies. The effects of sintering temperature, as well as nitrogen pressure, on the microstructure, density, and thermal conductivity of AlN ceramics were systematically discussed. A high thermal conductivity of 168 W·m-1·K-1 was achieved by sintering and holding at a significantly reduced temperature of 1720 °C with the assistance of a 0.6 MPa nitrogen-gas pressure. Further, a large-sized AlN ceramic plate and a heat sink with an internal mini-channel structure were designed and successfully fabricated by using the optimized printing and sintering parameters proposed in this study. The heat transfer performance of the ceramic heat sink was evaluated by infrared thermal imaging, showing excellent cooling abilities, which provides new opportunities for the development of ceramic heat dissipation modules with complex geometries and superior thermal management properties.

Three-Dimensional Printing of Molecularly Imprinted Polymers by Digital Light Processing for Copper Ion Sequestration.

Highly structured, molecularly imprinted polymer (MIP) networks for copper(II) ion sequestration have been realized using the additive manufacturing technology. Photopolymerizable formulations with acrylic functional monomers and two different porogens (water and methanol) in different ratios were studied to produce emulsions with 50 vol% of the internal phase. The results of morphological characterization indicate that all MIPs have cauliflower-like multiscale structures that change as a function of the solvent combination and fabrication process. X-ray fluorescence microscopy maps presented a layered structure and homogeneous distribution of copper in the printed MIP. Copper(II) ion adsorption-desorption tests were performed on MIPs prepared using a three-dimensional (3D) printing approach and MIPs prepared by bulk polymerization. Results indicate that the 3D printed MIP is able to absorb copper up to ten times more efficiently than the nonprinted one and the printed MIP with 100% water content has the highest imprint recognition.

Voxel Design of Grayscale DLP 3D-Printed Soft Robots.

Grayscale digital light processing (DLP) printing is a simple yet effective way to realize the variation of material properties by tuning the grayscale value. However, there is a lack of available design methods for grayscale DLP 3D-printed structures due to the complexities arising from the voxel-level grayscale distribution, nonlinear material properties, and intricate structures. Inspired by the dexterous motions of natural organisms, a design and fabrication framework for grayscale DLP-printed soft robots is developed by combining a grayscale-dependent hyperelastic constitutive model and a voxel-based finite-element model. The constitutive model establishes the relationship between the projected grayscale value and the nonlinear mechanical properties, while the voxel-based finite-element model enables fast and efficient calculation of the mechanical performances with arbitrarily distributed material properties. A multiphysics modeling and experimental method is developed to validate the homogenization assumption of the degree of conversion (DoC) variation in a single voxel. The design framework is used to design structures with reduced stress concentration and programmable multimodal motions. This work paves the way for integrated design and fabrication of functional structures using grayscale DLP 3D printing.

Innovative technologies for the fabrication of 3D/4D smart hydrogels and its biomedical applications - A comprehensive review.

Repairing and regenerating damaged tissues or organs, and restoring their functioning has been the ultimate aim of medical innovations. 'Reviving healthcare' blends tissue engineering with alternative techniques such as hydrogels, which have emerged as vital tools in modern medicine. Additive manufacturing (AM) is a practical manufacturing revolution that uses building strategies like molding as a viable solution for precise hydrogel manufacturing. Recent advances in this technology have led to the successful manufacturing of hydrogels with enhanced reproducibility, accuracy, precision, and ease of fabrication. Hydrogels continue to metamorphose as the vital compatible bio-ink matrix for AM. AM hydrogels have paved the way for complex 3D/4D hydrogels that can be loaded with drugs or cells. Bio-mimicking 3D cell cultures designed via hydrogel-based AM is a groundbreaking in-vivo assessment tool in biomedical trials. This brief review focuses on preparations and applications of additively manufactured hydrogels in the biomedical spectrum, such as targeted drug delivery, 3D-cell culture, numerous regenerative strategies, biosensing, bioprinting, and cancer therapies. Prevalent AM techniques like extrusion, inkjet, digital light processing, and stereo-lithography have been explored with their setup and methodology to yield functional hydrogels. The perspectives, limitations, and the possible prospects of AM hydrogels have been critically examined in this study.

Three-Dimensional-Printed GelMA-KerMA Composite Patches as an Innovative Platform for Potential Tissue Engineering of Tympanic Membrane Perforations.

Tympanic membrane (TM) perforations, primarily induced by middle ear infections, the introduction of foreign objects into the ear, and acoustic trauma, lead to hearing abnormalities and ear infections. We describe the design and fabrication of a novel composite patch containing photocrosslinkable gelatin methacryloyl (GelMA) and keratin methacryloyl (KerMA) hydrogels. GelMA-KerMA patches containing conical microneedles in their design were developed using the digital light processing (DLP) 3D printing approach. Following this, the patches were biofunctionalized by applying a coaxial coating with PVA nanoparticles loaded with gentamicin (GEN) and fibroblast growth factor (FGF-2) with the Electrohydrodynamic Atomization (EHDA) method. The developed nanoparticle-coated 3D-printed patches were evaluated in terms of their chemical, morphological, mechanical, swelling, and degradation behavior. In addition, the GEN and FGF-2 release profiles, antimicrobial properties, and biocompatibility of the patches were examined in vitro. The morphological assessment verified the successful fabrication and nanoparticle coating of the 3D-printed GelMA-KerMA patches. The outcomes of antibacterial tests demonstrated that GEN@PVA/GelMA-KerMA patches exhibited substantial antibacterial efficacy against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Furthermore, cell culture studies revealed that GelMA-KerMA patches were biocompatible with human adipose-derived mesenchymal stem cells (hADMSC) and supported cell attachment and proliferation without any cytotoxicity. These findings indicated that biofunctional 3D-printed GelMA-KerMA patches have the potential to be a promising therapeutic approach for addressing TM perforations.

Improving the 3D Printability and Mechanical Performance of Biorenewable Soybean Oil-Based Photocurable Resins.

The general requirement of replacing petroleum-derived plastics with renewable resources is particularly challenging for new technologies such as the additive manufacturing of photocurable resins. In this work, the influence of mono- and bifunctional reactive diluents on the printability and performance of resins based on acrylated epoxidized soybean oil (AESO) was explored. Polyethylene glycol di(meth)acrylates of different molecular weights were selected as diluents based on the viscosity and mechanical properties of their binary mixtures with AESO. Ternary mixtures containing 60% AESO, polyethylene glycol diacrylate (PEGDA) and polyethyleneglycol dimethacrylate (PEG200DMA) further improved the mechanical properties, water resistance and printability of the resin. Specifically, the terpolymer AESO/PEG575/PEG200DMA 60/20/20 (wt.%) improved the modulus (16% increase), tensile strength (63% increase) and %deformation at the break (21% increase), with respect to pure AESO. The enhancement of the printability provided by the reactive diluents was proven by Jacobs working curves and the improved accuracy of printed patterns. The proposed formulation, with a biorenewable carbon content of 67%, can be used as the matrix of innovative resins with unrestricted applicability in the electronics and biomedical fields. However, much effort must be done to increase the array of bio-based raw materials.