Nanoparticle-based nanocomposite coatings with postprocessing for enhanced antimicrobial capacity of polymeric film.

Bacterial adhesion and biofilm formation on surfaces pose a significant risk of microbial contamination and chronic diseases, leading to potential health complications. To mitigate this concern, the implementation of antibacterial coatings becomes paramount in reducing pathogen propagation on contaminated surfaces. To address this requirement, our study focuses on developing cost-effective and sustainable methods using polymer composite coatings. Copper and titanium dioxide nanoparticles were used to assess their active antimicrobial functions. After coating the surface with nanoparticles, four different combinations of two postprocessing treatments were performed. Intense pulsed light was utilized to sinter the coatings further, and plasma etching was applied to manipulate the physical properties of the nanocomposite-coated sheet surface. Bacterial viability was comparatively analyzed at four different time points (0, 30, 60, and 120 min) upon contact with the nanocomposite coatings. The samples with nanoparticle coatings and postprocessing treatments showed an above-average 84.82% mortality rate at 30 min and an average of 89.77% mortality rate at 120 min of contact. In contrast, the control sample, without nanoparticle coatings and postprocessing treatments, showed a 95% microbe viability after 120 min of contact. Through this study, we gained critical insights into effective strategies for preventing the spread of microorganisms on high-touch surfaces, thereby contributing to the advancement of sustainable antimicrobial coatings.

High Throughput Screening of Cell Mechanical Response Using a Stretchable 3D Cellular Microarray Platform.

Cells in vivo are constantly subjected to multiple microenvironmental mechanical stimuli that regulate cell function. Although 2D cell responses to the mechanical stimulation have been established, these methods lack relevance as physiological cell microenvironments are in 3D. Moreover, the existing platforms developed for studying the cell responses to mechanical cues in 3D either offer low-throughput, involve complex fabrication, or do not allow combinatorial analysis of multiple cues. Considering this, a stretchable high-throughput (HT) 3D cell microarray platform is presented that can apply dynamic mechanical strain to cells encapsulated in arrayed 3D microgels. The platform uses inkjet-bioprinting technique for printing cell-laden gelatin methacrylate (GelMA) microgel array on an elastic composite substrate that is periodically stretched. The developed platform is highly biocompatible and transfers the applied strain from the stretched substrate to the cells. The HT analysis is conducted to analyze cell mechano-responses throughout the printed microgel array. Also, the combinatorial analysis of distinct cell behaviors is conducted for different GelMA microenvironmental stiffnesses in addition to the dynamic stretch. Considering its throughput and flexibility, the developed platform can readily be scaled up to introduce a wide range of microenvironmental cues and to screen the cell responses in a HT way.

High-throughput investigation of endothelial-to-mesenchymal transformation (EndMT) with combinatorial cellular microarrays.

In the developing heart, a specific subset of endocardium undergoes an endothelial-to-mesenchymal transformation (EndMT) thus forming nascent valve leaflets. Extracellular matrix (ECM) proteins and growth factors (GFs) play important roles in regulating EndMT but the combinatorial effect of GFs with ECM proteins is less well understood. Here we use microscale engineering techniques to create single, binary, and tertiary component microenvironments to investigate the combinatorial effects of ECM proteins and GFs on the attachment and transformation of adult ovine mitral valve endothelial cells to a mesenchymal phenotype. With the combinatorial microenvironment microarrays, we utilized 60 different combinations of ECM proteins (Fibronectin, Collagen I, II, IV, Laminin) and GFs (TGF-ß1, bFGF, VEGF) and were able to identify new microenvironmental conditions capable of modulating EndMT in MVECs. Experimental results indicated that TGF-ß1 significantly upregulated the EndMT while either bFGF or VEGF downregulated EndMT process markedly. Also, ECM proteins could influence both the attachment of MVECs and the response of MVECs to GFs. In terms of attachment, fibronectin is significantly better for the adhesion of MVECs among the five tested proteins. Overall collagen IV and fibronectin appeared to play important roles in promoting EndMT process. Great consistency between macroscale and microarrayed experiments and present studies demonstrates that high-throughput cellular microarrays are a promising approach to study the regulation of EndMT in valvular endothelium. Biotechnol. Bioeng. 2016;113: 1403-1412. © 2015 Wiley Periodicals, Inc.

Multiscale stress-strain characterization of onion outer epidermal tissue in wet and dry states.

UNLABELLED: • PREMISE OF THE STUDY: Quantitative measurements of water's effects on the tension response of plant tissue will assist in understanding the regulatory mechanism underlying expansive growth. Such measurements should be multiscale in nature to account for plants' hierarchical structure.• METHODS: Outer onion epidermal tissues were cut and bonded to uniaxial displacement-controlled mechanical loading devices to apply and measure the force on the sample. Fluorescent polystyrene beads (500 nm in diameter) were dispersed on the sample surface under various levels of tensile load conditions to obtain displacement maps with a confocal fluorescent microscope. The resulting strain was measured using a digital image correlation technique by tracking individual bead displacements. The applied forces were obtained by measuring the displacement of the calibrated force-sensing device. Tissue- and cell-scale mechanical properties were quantified by calculating the applied stress and the corresponding global and local strains.• KEY RESULTS: The Young's modulus values of individual cell walls of dehydrated and rehydrated samples were 3.0 ± 1.0 GPa and 0.4 ± 0.2 GPa, respectively, and are different from the Young's modulus values of the global tissue-scale dehydrated and rehydrated samples, which were 1.9 ± 0.3 GPa and 0.08 ± 0.02 GPa, respectively. Poisson's ratio increased more than 3-fold due to hydration.• CONCLUSION: The results on global, cell-to-cell, and point-to-point mechanical property variations suggest the importance of the mechanical contribution of extracellular features including the middle lamella, cell shape, and dimension. This study shows that a multiscale investigation is essential for fundamental insights into the hierarchical deformation of biological systems.

Microfluidics-assisted fabrication of gelatin-silica core-shell microgels for injectable tissue constructs.

Microfabrication technology provides a highly versatile platform for engineering hydrogels used in biomedical applications with high-resolution control and injectability. Herein, we present a strategy of microfluidics-assisted fabrication photo-cross-linkable gelatin microgels, coupled with providing protective silica hydrogel layer on the microgel surface to ultimately generate gelatin-silica core-shell microgels for applications as in vitro cell culture platform and injectable tissue constructs. A microfluidic device having flow-focusing channel geometry was utilized to generate droplets containing methacrylated gelatin (GelMA), followed by a photo-cross-linking step to synthesize GelMA microgels. The size of the microgels could easily be controlled by varying the ratio of flow rates of aqueous and oil phases. Then, the GelMA microgels were used as in vitro cell culture platform to grow cardiac side population cells on the microgel surface. The cells readily adhered on the microgel surface and proliferated over time while maintaining high viability (∼90%). The cells on the microgels were also able to migrate to their surrounding area. In addition, the microgels eventually degraded over time. These results demonstrate that cell-seeded GelMA microgels have a great potential as injectable tissue constructs. Furthermore, we demonstrated that coating the cells on GelMA microgels with biocompatible and biodegradable silica hydrogels via sol-gel method provided significant protection against oxidative stress which is often encountered during and after injection into host tissues, and detrimental to the cells. Overall, the microfluidic approach to generate cell-adhesive microgel core, coupled with silica hydrogels as a protective shell, will be highly useful as a cell culture platform to generate a wide range of injectable tissue constructs.

Microfluidics-assisted rapid generation of tubular cell-laden microgel inside glass capillaries.

Drug screening using engineered blood vessels (EBVs) faces considerable barriers in approximating the conditions of an in vivo environment. To address this issue, we have introduced a microfluidic system for cell-laden tubular microgels. N-Carboxyethyl chitosan crosslinked with oxidized dextran was used for in situ gelable tubular scaffolds. The microfluidic system consisted of four glass capillaries that generated a coaxial flow of pre-polymer and phosphate buffered solutions. It rapidly produced cell-laden tubular microgels inside glass capillaries. The mechanical strength of the tubular microgels was suitable for their application as EBVs, with a maximum Young's modulus of 12.2 ± 1.9 kPa. In vitro cell studies using human umbilical vein endothelial cells verified the biocompatibility and non-cytotoxicity of the gelation and fabrication process. Thus, in situ gelable cell-laden tubular microgels can be a potential platform for screening drugs to treat blood vessel diseases.

An optical multi-sensing system for detection of cardiovascular toxicity.

A mini-microscope-based system for multisite detection of cardiovascular toxicity was developed. The mini-microscope consisted of an image sensor and lens module extracted from an inexpensive webcam. The flipped lens module enabled cells to be magnified and monitored during testing. The portability and compactness of this system enables short-term and potential long-term experimentation inside a conventional incubator. The toxicity test results demonstrated that the normalized beating rates of cardiac muscle cells selected from multiple regions increased over time when treated with 100 nM isoprenaline. The presented system could be a promising cost-effective cell-based testing tool for discovering and screening drugs.

Precision improvement of robotic bioprinting via vision-based tool path compensation.

Robotic 3D bioprinting is a rapidly advancing technology with applications in organ fabrication, tissue restoration, and pharmaceutical testing. While the stepwise generation of organs characterizes bioprinting, challenges such as non-linear material behavior, layer shifting, and trajectory tracking are common in freeform reversible embedding of suspended hydrogels (FRESH) bioprinting, leading to imperfections in complex organ construction. To overcome these limitations, we propose a computer vision-based strategy to identify discrepancies between printed filaments and the reference robot path. Employing error compensation techniques, we generate an adjusted reference path, enhancing robotic 3D bioprinting by adapting the robot path based on vision system data. Experimental assessments confirm the reliability and agility of our vision-based robotic 3D bioprinting approach, showcasing precision in fabricating human blood vessel segments through case studies. Significantly, it minimizes the printing layer width disparity to just 0.15 mm compared to the 0.6 mm in traditional methods, and it decreases the average error for curved filaments to 7.0 mm2 from the previous 12.7 mm2 in conventional printing. While these results underscore the significant potential of our innovation in creating precise biomimetic constructs, further investigation is necessary to tackle challenges such as accurately distinguishing closely stacked layers using a vision system, especially under varying lighting conditions. These limitations, coupled with issues of computational complexity and scalability in larger-scale bioprinting, emphasize the importance of enhancing the reliability of the vision-based approach across various conditions. Nonetheless, our innovation demonstrates substantial promise in creating precise biomimetic constructs and paves the way for future advancements in vision-guided robotic bioprinting, including the integration of multi-material printing techniques to enhance versatility.

Manipulating mechanical properties of PEG-based hydrogel nanocomposite: A potential versatile bio-adhesive for the suture-less repair of tissue.

Multifunctional bio-adhesives with tunable mechanical properties are obtained by controlling the orientation of anisotropic particles in a blend of fast-curing hydrogel with an imposed capillary flow. The suspensions' microstructural evolution was monitored by the small-angle light scattering (SALS) method during flow up to the critical Péclet number (Pe≈1) necessary for particle orientation and hydrogel crosslinking. The multifunctional bio-adhesives were obtained by combining flow and UV light exposure for rapid photo-curing of PEGDA medium and freezing titania rods' ordered microstructures. Blending the low- and high-molecular weight of PEGDA polymer improved the mechanical properties of the final hydrogel. All the hydrogel samples were non-cytotoxic up to 72 h after cell culturing. The system shows rapid blood hemostasis and promotes adhesive and cohesive strength matching targeted tissue properties with an applicating methodology compatible with surgical conditions. The developed SALS approach to optimize nanoparticles' microstructures in bio-adhesive applies to virtually any optically transparent nanocomposite and any type of anisotropic nanoparticles. As such, this method enables rational design of bio-adhesives with enhanced anisotropic mechanical properties which can be tailored to potentially any type of tissue.

Anisotropic hydrogel scaffold by flow-induced stereolithography 3D printing technique.

Essential organs, such as the heart and liver, contain a unique porous network that allows oxygen and nutrients to be exchanged, with distinct random to ordered regions displaying varying degrees of strength. A novel technique, referred to here as flow-induced lithography, was developed. This technique generates tunable anisotropic three-dimensional (3D) structures. The ink for this bioprinting technique was made of titanium dioxide nanorods (Ti) and kaolinite nanoclay (KLT) dispersed in a GelMA/PEGDA polymeric suspension. By controlling the flow rate, aligned particle microstructures were achieved in the suspensions. The application of UV light to trigger the polymerization of the photoactive prepolymer freezes the oriented particles in the polymer network. Because the viability test was successful in shearing suspensions containing cells, the flow-induced lithography technique can be used with both acellular scaffolds and cell-laden structures. Fabricated hydrogels show outstanding mechanical properties resembling human tissues, as well as significant cell viability (> 95 %) over one week. As a result of this technique and the introduction of bio-ink, a novel approach has been pioneered for developing anisotropic tissue implants utilizing low-viscosity biomaterials.

Sacrificial layer technique for axial force post assay of immature cardiomyocytes.

Immature primary and stem cell-derived cardiomyocytes provide useful models for fundamental studies of heart development and cardiac disease, and offer potential for patient specific drug testing and differentiation protocols aimed at cardiac grafts. To assess their potential for augmenting heart function, and to gain insight into cardiac growth and disease, tissue engineers must quantify the contractile forces of these single cells. Currently, axial contractile forces of isolated adult heart cells can only be measured by two-point methods such as carbon fiber techniques, which cannot be applied to neonatal and stem cell-derived heart cells because they are more difficult to handle and lack a persistent shape. Here we present a novel axial technique for measuring the contractile forces of isolated immature cardiomyocytes. We overcome cell manipulation and patterning challenges by using a thermoresponsive sacrificial support layer in conjunction with arrays of widely separated elastomeric microposts. Our approach has the potential to be high-throughput, is functionally analogous to current gold-standard axial force assays for adult heart cells, and prescribes elongated cell shapes without protein patterning. Finally, we calibrate these force posts with piezoresistive cantilevers to dramatically reduce measurement error typical for soft polymer-based force assays. We report quantitative measurements of peak contractile forces up to 146 nN with post stiffness standard error (26 nN) far better than that based on geometry and stiffness estimates alone. The addition of sacrificial layers to future 2D and 3D cell culture platforms will enable improved cell placement and the complex suspension of cells across 3D constructs.

Microfluidic fabrication of cell adhesive chitosan microtubes.

Chitosan has been used as a scaffolding material in tissue engineering due to its mechanical properties and biocompatibility. With increased appreciation of the effect of micro- and nanoscale environments on cellular behavior, there is increased emphasis on generating microfabricated chitosan structures. Here we employed a microfluidic coaxial flow-focusing system to generate cell adhesive chitosan microtubes of controlled sizes by modifying the flow rates of a chitosan pre-polymer solution and phosphate buffered saline (PBS). The microtubes were extruded from a glass capillary with a 300 µm inner diameter. After ionic crosslinking with sodium tripolyphosphate (TPP), fabricated microtubes had inner and outer diameter ranges of 70-150 µm and 120-185 µm. Computational simulation validated the controlled size of microtubes and cell attachment. To enhance cell adhesiveness on the microtubes, we mixed gelatin with the chitosan pre-polymer solution. During the fabrication of microtubes, fibroblasts suspended in core PBS flow adhered to the inner surface of chitosan-gelatin microtubes. To achieve physiological pH values, we adjusted pH values of chiotsan pre-polymer solution and TPP. In particular, we were able to improve cell viability to 92 % with pH values of 5.8 and 7.4 for chitosan and TPP solution respectively. Cell culturing for three days showed that the addition of the gelatin enhanced cell spreading and proliferation inside the chitosan-gelatin microtubes. The microfluidic fabrication method for ionically crosslinked chitosan microtubes at physiological pH can be compatible with a variety of cells and used as a versatile platform for microengineered tissue engineering.

Biofabrication of Cellulose-based Hydrogels for Advanced Wound Healing: A Special Emphasis on 3D Bioprinting.

Even with the current advancements in wound management, addressing most skin injuries and wounds continues to pose a significant obstacle for the healthcare industry. As a result, researchers are now focusing on creating innovative materials utilizing cellulose and its derivatives. Cellulose, the most abundant biopolymer in nature, has unique properties that make it a promising material for wound healing, such as biocompatibility, tunable physiochemical characteristics, accessibility, and low cost. 3D bioprinting technology has enabled the production of cellulose-based wound dressings with complex structures that mimic the extracellular matrix. The inclusion of bioactive molecules such as growth factors offers the ability to aid in promoting wound healing, while cellulose creates an ideal environment for controlled release of these biomolecules and moisture retention. The use of 3D bioprinted cellulose-based wound dressings has potential benefits for managing chronic wounds, burns, and painful wounds by promoting wound healing and reducing the risk of infection. This review provides an up-to-date summary of cellulose-based dressings manufactured by 3D bioprinting techniques by looking into wound healing biology, biofabrication methods, cellulose derivatives, and the existing cellulose bioinks targeted toward wound healing.

Recent Advances in Organ-on-Chips Integrated with Bioprinting Technologies for Drug Screening.

Currently, the demand for more reliable drug screening devices has made scientists and researchers develop novel potential approaches to offer an alternative to animal studies. Organ-on-chips are newly emerged platforms for drug screening and disease metabolism investigation. These microfluidic devices attempt to recapitulate the physiological and biological properties of different organs and tissues using human-derived cells. Recently, the synergistic combination of additive manufacturing and microfluidics has shown a promising impact on improving a wide array of biological models. In this review, different methods are classified using bioprinting to achieve the relevant biomimetic models in organ-on-chips, boosting the efficiency of these devices to produce more reliable data for drug investigations. In addition to the tissue models, the influence of additive manufacturing on microfluidic chip fabrication is discussed, and their biomedical applications are reviewed.

Closed-loop vasculature network design for bioprinting large, solid tissue scaffolds.

Vascularization is an indispensable requirement for fabricating large solid tissues and organs. The natural vasculature derived from medical imaging modalities for large tissues and organs are highly complex and convoluted. However, the present bioprinting capabilities limit the fabrication of such complex natural vascular networks. Simplified bioprinted vascular networks, on the other hand, lack the capability to sustain large solid tissues. This work proposes a generalized and adaptable numerical model to design the vasculature by utilizing the tissue/organ anatomy. Starting with processing the patient's medical images, organ structure, tissue-specific cues, and key vasculature tethers are determined. An open-source abdomen magnetic resonance image dataset was used in this work. The extracted properties and cues are then used in a mathematical model for guiding the vascular network formation comprising arterial and venous networks. Next, the generated three-dimensional networks are used to simulate the nutrient transport and consumption within the organ over time and the regions deprived of the nutrients are identified. These regions provide cues to evolve and optimize the vasculature in an iterative manner to ensure the availability of the nutrient transport throughout the bioprinted scaffolds. The mass transport of six components of cell culture media-glucose, glycine, glutamine, riboflavin, human serum albumin, and oxygen was studied within the organ with designed vasculature. As the vascular structure underwent iterations, the organ regions deprived of these key components decreased significantly highlighting the increase in structural complexity and efficacy of the designed vasculature. The numerical method presented in this work offers a valuable tool for designing vascular scaffolds to guide the cell growth and maturation of the bioprinted tissues for faster regeneration post bioprinting.

Visible light laser direct-writing of high-resolution, biocompatible, super-multifunctional and tough hydrogels without photoinitiators in 30 s.

Currently, the lack of bioinks and long printing time limits the further development of biofabrication. Here we report a novel biocompatible, multi-functional and tough 3D printable hydrogel via visible light photocrosslinking of polyvinyl alcohol bearing styrylpyridinium group (PVA-SbQ). The high-resolution PVA-SbQ hydrogels with different designed shapes can be generated via laser direct-writing in 30 s without extra toxic crosslinkers or photoinitiators, and demonstrates excellent biocompatibility. The rapid laser direct-writing technology also results in a super-strong, tough hydrogel with excellent adhesive, swelling, self-healing, and photo-tunable properties due to the photodimerization of styrylpyridinium (SbQ) groups and the left-over massive amount of free hydroxyl groups in the hydrogel. For example, the maximum tensile strength, elongation, compressive strength adhesive strength of printed PVA-SbQ hydrogels can reach 1.0 MPa, 810 %, 33 MPa, 31 kPa, and 25,000 % respectively. And these properties can be adjusted by controlling the parameters for laser direct-writing. In addition, the introduced nitrogen cations by SbQ groups further endow hydrogels with the potential to develop novel functionality, which is demonstrated by integrating negatively charged nanocelluloses in the PVA-SbQ system to develop underwater adhesives, anti-freezing (-24.9 °C), and anti-bacterial hydrogels. This discovery opens multiple doors for developing PVA-SbQ based multi-functional hydrogel for various applications including biofabrication and tissue engineering.

Development of Antifreezing, Printable, Adhesive, Tough, Biocompatible, High-Water Content Hydrogel for Versatile Applications.

Hydrogels with different functionalities such as printability, antifreezing properties, adhesion, biocompatibility, and toughness are being continually developed. However, it has been extremely challenging to design adhesive, antifreezing, tough, and biocompatible multifunctional hydrogels with complex shapes simultaneously and prepare them in a short period. In this paper, novel composite hydrogels, which consist of poly(vinyl alcohol) grafted with styrylpyridinium group (PVA-SbQ) and TEMPO-oxidized cellulose nanofibrils (CNF), were successfully synthesized via UV photo-cross-linking. In addition to UV photo-cross-linking, the PVA-SbQ/CNF hydrogels with different shapes could be rapidly printed by facile visible light-based stereolithography printing and laser direct-writing without any photoinitiators in 3 min and 30 s, respectively. The results show that PVA-SbQ/CNF hydrogels are biocompatible because there are no photoinitiators and cross-linkers required during the printing process under visible light. Moreover, the adhesive, antifreezing, mechanical properties, and water-binding capacity of PVA-SbQ/CNF with high-water contents improved significantly as the CNF contents increased. Such hydrogels, which combine multiple advantages, present great potential for application in wound dressings and portable devices with specific requirements for shapes, adhesion, toughness, and tolerance in extreme environments such as dry environments and low temperatures.

Optimized 3D Bioprinting Technology Based on Machine Learning: A Review of Recent Trends and Advances.

The need for organ transplants has risen, but the number of available organ donations for transplants has stagnated worldwide. Regenerative medicine has been developed to make natural organs or tissue-like structures with biocompatible materials and solve the donor shortage problem. Using biomaterials and embedded cells, a bioprinter enables the fabrication of complex and functional three-dimensional (3D) structures of the organs or tissues for regenerative medicine. Moreover, conventional surgical 3D models are made of rigid plastic or rubbers, preventing surgeons from interacting with real organ or tissue-like models. Thus, finding suitable biomaterials and printing methods will accelerate the printing of sophisticated organ structures and the development of realistic models to refine surgical techniques and tools before the surgery. In addition, printing parameters (e.g., printing speed, dispensing pressure, and nozzle diameter) considered in the bioprinting process should be optimized. Therefore, machine learning (ML) technology can be a powerful tool to optimize the numerous bioprinting parameters. Overall, this review paper is focused on various ideas on the ML applications of 3D printing and bioprinting to optimize parameters and procedures.

The Effect of Crosslinking Degree of Hydrogels on Hydrogel Adhesion.

The development of adhesive hydrogel materials has brought numerous advances to biomedical engineering. Hydrogel adhesion has drawn much attention in research and applications. In this paper, the study of hydrogel adhesion is no longer limited to the surface of hydrogels. Here, the effect of the internal crosslinking degree of hydrogels prepared by different methods on hydrogel adhesion was explored to find the generality. The results show that with the increase in crosslinking degree, the hydrogel adhesion decreased significantly due to the limitation of segment mobility. Moreover, two simple strategies to improve hydrogel adhesion generated by hydrogen bonding were proposed. One was to keep the functional groups used for hydrogel adhesion and the other was to enhance the flexibility of polymer chains that make up hydrogels. We hope this study can provide another approach for improving the hydrogel adhesion generated by hydrogen bonding.

Recent trends in gelatin methacryloyl nanocomposite hydrogels for tissue engineering.

Gelatin methacryloyl (GelMA), a photocrosslinkable gelatin-based hydrogel, has been immensely used for diverse applications in tissue engineering and drug delivery. Apart from its excellent functionality and versatile mechanical properties, it is also suitable for a wide range of fabrication methodologies to generate tissue constructs of desired shapes and sizes. Despite its exceptional characteristics, it is predominantly limited by its weak mechanical strength, as some tissue types naturally possess high mechanical stiffness. The use of high GelMA concentrations yields high mechanical strength, but not without the compromise in its porosity, degradability, and three-dimensional (3D) cell attachment. Recently, GelMA has been blended with various natural and synthetic biomaterials to reinforce its physical properties to match with the tissue to be engineered. Among these, nanomaterials have been extensively used to form a composite with GelMA, as they increase its biological and physicochemical properties without affecting the unique characteristics of GelMA and also introduce electrical and magnetic properties. This review article presents the recent advances in the formation of hybrid GelMA nanocomposites using a variety of nanomaterials (carbon, metal, polymer, and mineral-based). We give an overview of each nanomaterial's characteristics followed by a discussion of the enhancement in GelMA's physical properties after its incorporation. Finally, we also highlight the use of each GelMA nanocomposite for different applications, such as cardiac, bone, and neural regeneration.