Three-Dimensional Printing Strategies for Enhanced Hydrogel Applications

This study explores the dynamic field of 3D-printed hydrogels, emphasizing advancements and challenges in customization, fabrication, and functionalization for applications in biomedical engineering, soft robotics, and tissue engineering. It delves into the significance of tailored biomedical scaffolds for tissue regeneration, the enhancement in bioinks for realistic tissue replication, and the development of bioinspired actuators. Additionally, this paper addresses fabrication issues in soft robotics, aiming to mimic biological structures through high-resolution, multimaterial printing. In tissue engineering, it highlights efforts to create environments conducive to cell migration and functional tissue development. This research also extends to drug delivery systems, focusing on controlled release and biocompatibility, and examines the integration of hydrogels with electronic components for bioelectronic applications. The interdisciplinary nature of these efforts highlights a commitment to overcoming material limitations and optimizing fabrication techniques to realize the full potential of 3D-printed hydrogels in improving health and well-being.


Introduction
The field of 3D-printed hydrogels has emerged as a dynamic and rapidly evolving area of research, driven by a diverse array of needs and challenges across various applications (Scheme 1).At the core of this innovative domain is the pursuit of advancing the customization, fabrication, and functionalization of hydrogels to meet specific requirements in biomedical engineering, soft robotics, tissue engineering, and beyond.
Customization of biomedical scaffolds for optimal tissue regeneration [1] remains a pivotal challenge, underscoring the importance of tailored solutions for individual patient needs.This necessity merges with the advancements in multimaterial 3D printing, enabling the creation of structures with unprecedented complexity and functionality.Researchers are also focused on enhancing the mechanical properties of bioinks [2], crucial for the realistic replication of biological tissues and the development of bioinspired actuators [3].
Fabrication challenges are pronounced in the domain of soft robotics, where the replication of soft material 3D printing [4] and embedding long fibers in hydrogels [5] are explored to mimic complex biological structures and functions.The quest for highresolution, multimaterial, 3D hydrogel structures [6] further exemplifies the technical hurdles in achieving precise and scalable manufacturing techniques.
In tissue engineering, the creation of supportive environments for cell migration [7], nutrient/oxygen transport [8], and vasculature networks [9] is essential for the development of functional tissue constructs.This includes overcoming the natural limitations of hydrogel materials, such as the spread of wet droplets [10] and rapid solidification for photocrosslinking [11], to achieve desired geometries and properties.
hancing biocompatibility and mechanical strength [22,23] to achieving precision in nanoparticle arrangement [24] and optimizing scaffold fabrication [25], the field is characterized by a relentless pursuit of solutions that bridge the gap between theoretical potential and practical application.As researchers continue to address these challenges, the field of 3D-printed hydrogels stands on the border of significant breakthroughs that promise to transform a wide range of industries and improve human health and well-being.Scheme 1.General challenges in 3D printing for biomedical applications.

Recent Studies on 3D-Printed Hydrogels
The study of 3D-printed hydrogels in the fields of material science and engineering is a rapidly evolving area focused on enhancing processing techniques, improving material properties, and integrating functional features.This work aims to expand the use of these materials across various disciplines.Key areas of research and development include the following: 1. Advancing photopolymerization methods and creating both thermoresponsive and biodegradable hydrogels to enhance their mechanical and physical characteristics.2. Adding functional additives and creating new composites to address the limitations of hydrogels, thus improving their utility in sophisticated manufacturing and design applications.
Scheme 1.General challenges in 3D printing for biomedical applications.
The application of 3D-printed hydrogels extends into the domain of drug delivery [12,13], where controlled release mechanisms and biocompatibility are paramount.Similarly, the development of high-strength and ultratough hydrogels [14,15] addresses the need for materials that can withstand mechanical stresses while maintaining flexibility and biocompatibility for implantable devices.
Emerging applications also highlight the integration of hydrogels with electronic components [16,17], paving the way for innovative bioelectronics that can monitor and interact with biological systems in real-time.The development of conductive hydrogels [18,19] and self-healing materials [20,21] reflects the interdisciplinary nature of current research efforts, blending materials science with electrical engineering to create multifunctional devices.
The challenges and needs identified across these diverse applications demonstrate the interdisciplinary and innovative nature of research in 3D-printed hydrogels.From enhancing biocompatibility and mechanical strength [22,23] to achieving precision in nanoparticle arrangement [24] and optimizing scaffold fabrication [25], the field is characterized by a relentless pursuit of solutions that bridge the gap between theoretical potential and practical application.As researchers continue to address these challenges, the field of 3D-printed hydrogels stands on the border of significant breakthroughs that promise to transform a wide range of industries and improve human health and well-being.

Recent Studies on 3D-Printed Hydrogels
The study of 3D-printed hydrogels in the fields of material science and engineering is a rapidly evolving area focused on enhancing processing techniques, improving material properties, and integrating functional features.This work aims to expand the use of these materials across various disciplines.Key areas of research and development include the following: 1.
Advancing photopolymerization methods and creating both thermoresponsive and biodegradable hydrogels to enhance their mechanical and physical characteristics.

2.
Adding functional additives and creating new composites to address the limitations of hydrogels, thus improving their utility in sophisticated manufacturing and design applications.

3.
Designing materials that replicate biological systems for use in biofabrication and tissue engineering, which involves improving mechanical properties, responsiveness to stimuli, and functional complexity.This opens new possibilities in regenerative medicine, soft robotics, and other areas.4.
Developing materials for tissue engineering and scaffolding that include bioactive molecules and porous structures, which support cell activity and closely resemble the natural tissue environment for advanced tissue regeneration.5.
Innovating in the field of biomedical devices and drug delivery by integrating bioactive molecules, enhancing mechanical and functional properties, and devising controlled release mechanisms tailored to specific medical treatments.6.
Advancing sensor technology and electronics with the use of conductive, responsive, and bioactive materials to create devices that are flexible, sensitive, and multifunctional.These devices have applications in wearable technology, soft robotics, and bioelectronics.7.
Focusing on the creation of advanced actuators and robotic systems for soft robotics, which are made from materials that exhibit superior mechanical properties and responsiveness for complex movements and mimicking biological functions.8.
Investigating the use of hydrogels in environmental and energy sectors to support sustainable energy production, agricultural development, and environmental cleanup, making use of their unique characteristics for innovative and sustainable solutions.
These initiatives demonstrate a strategic approach to leveraging 3D-printed hydrogels, emphasizing the continuous effort to refine material properties, broaden the scope of applications, and tackle significant challenges in science and technology.

Hydrogel Crosslinking
Hydrogel crosslinking plays a pivotal role in hydrogel bioprinting, serving as the cornerstone for designing scaffolds that mimic the extracellular matrix, enabling the controlled release of bioactive molecules, and encapsulating living cells.Crosslinking methods, both chemical and physical, are integral for tailoring hydrogel properties such as degradation rates, mechanical strength, and biocompatibility, which are crucial for various biomedical applications.
Chemical crosslinking is highlighted for its versatility in creating hydrogels with robust mechanical stability.This method allows for the precise design of hydrogels that can degrade under physiological conditions into non-toxic products, ensuring biocompatibility.However, the use of potentially toxic crosslinking agents necessitates their complete removal to avoid adverse reactions with bioactive substances present within the hydrogel matrix [26].In contrast, physical crosslinking methods offer an alternative that circumvents the use of toxic chemicals.These methods involve interactions that do not require covalent bond formation, thereby avoiding potential negative effects on the bioactive components embedded within the hydrogels.This advantage makes physically crosslinked hydrogels attractive for applications requiring high biocompatibility and functionality [26].
The development of interpenetrating networks through double crosslinking (covalent followed by ionic) not only enhances the hydrogel features but also allows for the modulation of hydrogel properties through the adjustment of preparation parameters.The use of neural network models to simulate and optimize these parameters further highlights the complexity and potential of hydrogel crosslinking in creating tailored matrices for drug delivery and cell encapsulation [27].
Exploring multifunctional crosslinking molecules has opened new avenues for regulating the degradation rates and mechanical properties of hydrogels.By comparing hydrogels formed with multifunctional versus bi-functional crosslinking molecules, it is evident that the former can provide superior mechanical stiffness and slower degradation rates, attributed to the increased crosslinking density and interaction points within the hydrogel network.This method demonstrates the importance of crosslinking chemistry in enhancing the performance of hydrogels for various biomedical applications [28].
Enzyme-catalyzed crosslinking represents an innovative and cell-friendly approach to hydrogel formation, offering a mild alternative to traditional chemical and physical crosslinking methods.This strategy enables the formation of covalently crosslinked hydrogels with complex architectures, mimicking the natural extracellular matrix more closely and providing dynamic scaffolds for tissue engineering and regenerative medicine.The shift towards enzymatic crosslinking features the evolving landscape of hydrogel preparation, where biocompatibility and functionality are paramount [29].
In situ crosslinking strategies for the 3D bioprinting of photo-crosslinkable hydrogels further illustrate the advancements in hydrogel technology.This approach enables the creation of complex, cell-laden constructs with high embedded cell viability and tunable cell behavior, featuring the critical role of crosslinking in the development of next-generation biofabricated tissues and organs [30].
Overall, the evolution of hydrogel crosslinking techniques-from chemical and physical to innovative enzymatic and in situ methods-demonstrates the field's continuous advancement towards creating more sophisticated, biocompatible, and functional hydrogel systems for a myriad of biomedical applications.

Three-Dimensional and 4D Bioprinting
The transition from three-dimensional (3D) printing to four-dimensional (4D) printing represents a significant advancement in additive manufacturing, shifting from static constructs to dynamic, responsive structures.This evolution is characterized by the development of platforms that can change their properties, shape, or functionality over time in response to external stimuli, leveraging the capabilities of stimuli-responsive materials [31].
Three-dimensional printing has laid the groundwork for this advancement by enabling the precise layer-by-layer construction of complex structures, where control over the dimensions and properties of the printed objects is paramount.Among the materials employed in 3D printing, hydrogels have emerged as particularly promising due to their biocompatibility and the ability to undergo reversible transformations.These properties have made hydrogels a key material in the progression towards 4D printing, where the goal is to create structures capable of adapting to their environment [32].
The core of 4D printing technology lies in the use of stimuli-responsive hydrogels.These materials can expand, contract, or otherwise change shape in response to environmental triggers, such as temperature changes or the presence of specific chemicals.This responsiveness to stimuli has opened new avenues for creating devices and structures with applications ranging from actuators and cellular scaffolds to controlled drug release systems.The versatility and low cost of manufacturing these hydrogel-based structures further enhance their appeal for a wide range of applications [31].
An innovative approach in the field involves the development of composite inks, such as those combining cellulose with hydrogels.These composites not only maintain the responsive characteristics of hydrogels but also incorporate the mechanical strength of cellulose fibers.This combination enables the fabrication of structures that can morph according to predetermined designs in response to environmental stimuli, such as moisture levels.Such advancements illustrate the potential of 4D printing in creating more complex, responsive, and durable structures [33].
Among the specific applications of 4D bioprinting, the development of smart valves stands out.These valves, fabricated from a blend of alginate and poly(N-isopropylacrylamide), exemplify the practical application of 4D printing in producing structures that are not only mechanically robust but also capable of actuating in response to temperature changes.This highlights the potential of 4D-printed hydrogels in creating dynamic, responsive systems with possible uses in fluid management and soft robotics [34].
A notable technique in this evolution involves printing stimuli-responsive hydrogel structures with internal gaps using a combination of responsive and non-responsive pregel solutions.By printing these materials in a supportive medium and then solidifying them with ultraviolet light, it is possible to create complex structures capable of dramatic transformations in response to thermal stimuli.This method highlights the sophisticated control over material properties and structural design that 4D printing offers, paving the way for the fabrication of intricate, responsive patterns and shapes [35].

Hydrogel Bioprinting Techniques
Bioprinting is an emerging field that merges engineering, biology, and medicine to innovate in areas such as tissue engineering and regenerative medicine.This field is notable for its application of several key techniques, extrusion-based bioprinting, inkjet bioprinting, and vat photopolymerization, each with unique mechanisms and uses [36].
Extrusion-based bioprinting (EBB) is akin to 3D printing, where biomaterials mixed with cells are pushed through a nozzle to build three-dimensional structures layer by layer.This method supports a broad viscosity range, accommodating various hydrogels and cellladen bioinks, making it adaptable for creating large, intricate structures while preserving high cell viability.Despite its versatility, it struggles with lower resolution and potential shear stress that may harm cell viability and functionality.The performance of EBB is affected by factors such as the viscosity of the hydrogel, the diameter of the nozzle, and the speed of printing.Recent progress has expanded its applications to include printing tissues, organ modules, and microfluidic devices.Nevertheless, challenges persist, including limitations in organ fabrication, feature resolution, and regulatory hurdles, indicating a need for advanced bioprinting solutions and new bioink development to bridge the gap from laboratory to clinical use, aiming to produce viable products for tissue engineering and regenerative medicine [37,38].Extrusion printing can be carried out on a surface or into a suspension bath or media.Figure 1 below shows how a bioink is deposited onto a surface or within a suspension bath with a pattern defined by the user.
changes.This highlights the potential of 4D-printed hydrogels in creating dynamic, responsive systems with possible uses in fluid management and soft robotics [34].
A notable technique in this evolution involves printing stimuli-responsive hydrogel structures with internal gaps using a combination of responsive and non-responsive pregel solutions.By printing these materials in a supportive medium and then solidifying them with ultraviolet light, it is possible to create complex structures capable of dramatic transformations in response to thermal stimuli.This method highlights the sophisticated control over material properties and structural design that 4D printing offers, paving the way for the fabrication of intricate, responsive patterns and shapes [35].

Hydrogel Bioprinting Techniques
Bioprinting is an emerging field that merges engineering, biology, and medicine to innovate in areas such as tissue engineering and regenerative medicine.This field is notable for its application of several key techniques, extrusion-based bioprinting, inkjet bioprinting, and vat photopolymerization, each with unique mechanisms and uses [36].
Extrusion-based bioprinting (EBB) is akin to 3D printing, where biomaterials mixed with cells are pushed through a nozzle to build three-dimensional structures layer by layer.This method supports a broad viscosity range, accommodating various hydrogels and cell-laden bioinks, making it adaptable for creating large, intricate structures while preserving high cell viability.Despite its versatility, it struggles with lower resolution and potential shear stress that may harm cell viability and functionality.The performance of EBB is affected by factors such as the viscosity of the hydrogel, the diameter of the nozzle, and the speed of printing.Recent progress has expanded its applications to include printing tissues, organ modules, and microfluidic devices.Nevertheless, challenges persist, including limitations in organ fabrication, feature resolution, and regulatory hurdles, indicating a need for advanced bioprinting solutions and new bioink development to bridge the gap from laboratory to clinical use, aiming to produce viable products for tissue engineering and regenerative medicine [37,38].Extrusion printing can be carried out on a surface or into a suspension bath or media.Figure 1 below shows how a bioink is deposited onto a surface or within a suspension bath with a pattern defined by the user.Inkjet bioprinting utilizes thermal or piezoelectric actuators to place droplets of bioink on a substrate, noted for its high precision and resolution.This method is cost-effective and straightforward but is limited to bioinks with low viscosity and faces potential cell damage from heat or mechanical stress.Factors like bioink viscosity and minimizing cell damage are vital for its performance.The drop-on-demand jetting approach allows for the non-contact deposition of materials and cells, optimizing cell-to-matrix and cell-to-cell interactions.Despite its advantages, the effect of bioink properties on printing performance and cell health is not fully understood.Research indicates that bioink viscoelasticity and viscosity are crucial for printing accuracy and cell viability, emphasizing the importance of bioink formulation for precise cell deposition and the creation of adjustable cell spheroids [39,40].
Vat photopolymerization involves the selective curing of photosensitive polymers or hydrogels with light to create solid 3D structures.It is distinguished by its high resolution and ability to produce complex shapes but is limited to photosensitive materials and the potential toxicity from photoinitiators.The technique's performance depends on the choice and concentration of photoinitiators, as well as optimizing light intensity and exposure time.Recent developments in vat polymerization-based 3D printing and bioprinting have introduced new biomaterial ink formulations and system designs, with the expectation of their swift application in biomedical fields.This indicates a concerted effort to combine innovative vat polymerization techniques with biomaterial inks for better medical outcomes [41,42].The patterns projected are typically derived from computerized 3D drawings or from CT scans or MRIs of patients' resources.These patterns are designed using vat polymerization before remodeling to create patient-specific medical devices, functional human tissues for regeneration, and in vitro human-based tissue models for therapeutic screening, as illustrated in Figure 2 below.ink on a substrate, noted for its high precision and resolution.This method is cost-effective and straightforward but is limited to bioinks with low viscosity and faces potential cell damage from heat or mechanical stress.Factors like bioink viscosity and minimizing cell damage are vital for its performance.The drop-on-demand jetting approach allows for the non-contact deposition of materials and cells, optimizing cell-to-matrix and cell-to-cell interactions.Despite its advantages, the effect of bioink properties on printing performance and cell health is not fully understood.Research indicates that bioink viscoelasticity and viscosity are crucial for printing accuracy and cell viability, emphasizing the importance of bioink formulation for precise cell deposition and the creation of adjustable cell spheroids [39,40].
Vat photopolymerization involves the selective curing of photosensitive polymers or hydrogels with light to create solid 3D structures.It is distinguished by its high resolution and ability to produce complex shapes but is limited to photosensitive materials and the potential toxicity from photoinitiators.The technique's performance depends on the choice and concentration of photoinitiators, as well as optimizing light intensity and exposure time.Recent developments in vat polymerization-based 3D printing and bioprinting have introduced new biomaterial ink formulations and system designs, with the expectation of their swift application in biomedical fields.This indicates a concerted effort to combine innovative vat polymerization techniques with biomaterial inks for better medical outcomes [41,42].The patterns projected are typically derived from computerized 3D drawings or from CT scans or MRIs of patients' resources.These patterns are designed using vat polymerization before remodeling to create patient-specific medical devices, functional human tissues for regeneration, and in vitro human-based tissue models for therapeutic screening, as illustrated in Figure 2 below.In hydrogel bioprinting, selecting a bioprinting technique usually depends on the requirements of the desired application, such as the complexity of the structure, mechanical properties, and biological functionality.The composition of the hydrogel, the type of cells used, and the purpose of the application are crucial in determining the most appropriate bioprinting method.Ongoing research and development aim to address current limitations and expand the possibilities of bioprinting technologies, leading to the creation of more complex and functional bioprinted tissues and organs [43].In hydrogel bioprinting, selecting a bioprinting technique usually depends on the requirements of the desired application, such as the complexity of the structure, mechanical properties, and biological functionality.The composition of the hydrogel, the type of cells used, and the purpose of the application are crucial in determining the most appropriate bioprinting method.Ongoing research and development aim to address current limitations and expand the possibilities of bioprinting technologies, leading to the creation of more complex and functional bioprinted tissues and organs [43].
Recent advancements in 3D printing technologies, particularly in material and process optimization, have led to significant developments across various fields, including tissue engineering, regenerative medicine, soft robotics, and biomedical applications.These innovations demonstrate a concerted effort towards creating more sustainable, efficient, and customized solutions.Figure 3 below shows sample morphologies printed with GT-AT-MMT bioinks of variable concentrations under predetermined pressures.
Recent advancements in 3D printing technologies, particularly in material and process optimization, have led to significant developments across various fields, including tissue engineering, regenerative medicine, soft robotics, and biomedical applications.These innovations demonstrate a concerted effort towards creating more sustainable, efficient, and customized solutions.Figure 3 below shows sample morphologies printed with GT-AT-MMT bioinks of variable concentrations under predetermined pressures.In tissue engineering and regenerative medicine, the customization of bio-based scaffolds has been a notable achievement.These scaffolds, with controlled pore sizes and gradient structures, are designed to enhance tissue regeneration capabilities [1].The optimization of 3D inkjet printing techniques for alginate bioinks has facilitated the creation of structures that closely mimic tissue, supporting physiological flows [10].Additionally, the introduction of hydrogel-based technologies has marked a significant stride in cell therapy and tissue engineering applications, offering precise size control for cell therapy and tissue engineering applications [44] and optimizing cell-friendly fabrication for physiological models [9].This is complemented by developments in bone regeneration, where MXene composite hydrogels have demonstrated synergistic antibacterial and osteogenic effects [45], and in drug delivery systems, where thermosensitive hydrogels show potential for controlled drug release [13].
The field of soft and marine robotics has also seen innovative applications of 3D printing technologies.The fabrication of jellyfish-mimic soft robot actuators [4] and biodegradable hydrogel actuators [46] illustrates the potential of these technologies in developing devices that operate effectively in challenging environments.Furthermore, the In tissue engineering and regenerative medicine, the customization of bio-based scaffolds has been a notable achievement.These scaffolds, with controlled pore sizes and gradient structures, are designed to enhance tissue regeneration capabilities [1].The optimization of 3D inkjet printing techniques for alginate bioinks has facilitated the creation of structures that closely mimic tissue, supporting physiological flows [10].Additionally, the introduction of hydrogel-based technologies has marked a significant stride in cell therapy and tissue engineering applications, offering precise size control for cell therapy and tissue engineering applications [44] and optimizing cell-friendly fabrication for physiological models [9].This is complemented by developments in bone regeneration, where MXene composite hydrogels have demonstrated synergistic antibacterial and osteogenic effects [45], and in drug delivery systems, where thermosensitive hydrogels show potential for controlled drug release [13].
The field of soft and marine robotics has also seen innovative applications of 3D printing technologies.The fabrication of jellyfish-mimic soft robot actuators [4] and biodegradable hydrogel actuators [46] illustrates the potential of these technologies in developing devices that operate effectively in challenging environments.Furthermore, the advancement in material properties, such as full-color luminescence and opacity tuning [3], enhances the adaptability and utility of robotic systems.
Hydrogel technologies have been central to overcoming fabrication limitations and introducing novel functionalities.The development of multiscale, multimaterial 3D hydrogel structures [6] and the improvement in mechanical properties through hydrogel composites [47] are exemplary.Moreover, photocrosslinking techniques for silk-fibroin-based hydrogels [11] and the use of a hydrogel pen for nanometer precision in 3D printing [48] highlight the ongoing efforts in process optimization.
Material science has played a crucial role in these advancements, with the exploration of hydrogel printability [49], rapid hydrogel bead fabrication [44], and the engineering of perfusable vasculature networks on-chip [9] being notable examples.These efforts not only enhance the practical applications of 3D printing technologies but also contribute to the broader understanding of material interactions and fabrication processes.
In conclusion, the advancements in 3D printing technologies stress the dynamic and interdisciplinary nature of this field.By pushing the boundaries of material and process optimization, these innovations offer promising solutions to complex challenges across science, medicine, and engineering.Table 1 below shows the different printing technologies, materials used and their applications.

Scaffold Mechanical Enhancement and Biocompatibility
The recent advancements in scaffold design, particularly in enhancing mechanical properties and biocompatibility, signify a critical trend in tissue engineering, regenerative medicine, and material science.These advancements, as evidenced by numerous studies, are foundational to the development of scaffolds that support cellular growth and tissue integration effectively.For instance, the improvement in the mechanical properties of sodium alginate through the incorporation of agarose has been noted to facilitate cell growth, thanks to the scaffold's designed micro-pores [56].Additionally, the enhancement in hydrogel scaffolds with microtubes has shown promising results in terms of mechanical strength and biocompatibility, demonstrating the potential for application in soft tissue engineering [23].Figure 4 below shows the core-sheath spinneret set up for the production of the microtubules and the SEM images of the microtubules produced.
The role of 3D printing technology in scaffold fabrication has evolved significantly, enabling the creation of complex structures tailored for specific applications.Innovations such as multiple-layered hydrogel scaffold printing [57], 3D-printed metal foams integrated with hydrogel for bone replacement [58], and the use of photopolymerizable copolypeptides for producing mechanically robust 3D objects [59] exemplify the versatility and precision offered by 3D printing techniques.These advancements highlight the industry's move towards employing manufacturing technologies that allow for customized scaffold designs with enhanced functionality.
There is a growing emphasis on developing scaffolds that offer multifunctional capabilities, such as improved osseointegration, antibacterial properties [60], and conductivity conducive to neuron growth [61].This trend towards multifunctionality reflects a shift in focus towards creating scaffolds that not only support tissue growth but also integrate additional features to enhance the overall therapeutic outcome.
Environmental sustainability and safety in scaffold materials have emerged as important considerations.The development of biodegradable cellulose hydrogel inks for 3D printing metal structures [62] represents a step towards more environmentally friendly and safer additive manufacturing processes.This focus on sustainability indicates a broader commitment within the field to reduce environmental impact and enhance patient safety through innovative material choices.medicine, and material science.These advancements, as evidenced by numerous studies, are foundational to the development of scaffolds that support cellular growth and tissue integration effectively.For instance, the improvement in the mechanical properties of sodium alginate through the incorporation of agarose has been noted to facilitate cell growth, thanks to the scaffold's designed micro-pores [56].Additionally, the enhancement in hydrogel scaffolds with microtubes has shown promising results in terms of mechanical strength and biocompatibility, demonstrating the potential for application in soft tissue engineering [23].Figure 4 below shows the core-sheath spinneret set up for the production of the microtubules and the SEM images of the microtubules produced.The role of 3D printing technology in scaffold fabrication has evolved significantly, enabling the creation of complex structures tailored for specific applications.Innovations such as multiple-layered hydrogel scaffold printing [57], 3D-printed metal foams Moreover, the exploration of scaffold materials for applications beyond traditional tissue engineering showcases the adaptability and potential of these materials in cutting-edge fields.For example, the utilization of scaffolds in soft robotics [63], flexible electronics [16], and space agriculture [64] demonstrates the broad applicability and versatility of scaffold materials, paving the way for novel technological advancements.
In summary, the trends highlighted by recent research in scaffold mechanical enhancement and biocompatibility reflect a dynamic field characterized by innovation in material properties, manufacturing techniques, and application domains.The integration of enhanced mechanical and biological properties, coupled with the advancements in 3D printing technology, multifunctionality, environmental sustainability, and novel applications, emphasize the ongoing evolution of scaffold technology (Table 2).

Stretchable and Conductive Hydrogels
Recent advancements in the field of stretchable and conductive hydrogels have marked significant milestones across several applications, including but not limited to soft robotics, tissue engineering, human motion detection, and soft bioelectronics.These innovations are primarily driven by the integration of advanced printing techniques with hydrogel technology, the development of conductive hydrogels with enhanced functionalities, pioneering applications in soft bioelectronics and sensing, and innovations in sensing and energy generation.
The integration of advanced printing techniques with hydrogel technology has led to notable achievements.The high-resolution printing of stretchable double-network (DN) hydrogels has addressed the shaping challenges in soft robotics and tissue engineering, facilitated by quick lithography techniques [89].Further, the field has seen the development of ultrastretchable and self-healing DN hydrogel printing, which exhibits remarkable mechanical strength and strain sensitivity, crucial for robotics and human motion detection [90].
Additionally, the introduction of a cryogenic 3D printing method for conductive hydrogel inks has produced cytocompatible, conductive scaffolds suitable for tissue engineering applications [91].
The development of conductive hydrogels with enhanced functionalities has also been a key area of progress.The coupling of 3D printing with interfacial polymerization has enabled the creation of conductive hydrogels with complex geometries, paving the way for the development of electroactive materials with precisely defined structures for advanced applications [92].Moreover, the development of ultrasensitive and self-adhesive wearable devices with exceptional conductivity and stretchability has advanced motion monitoring and health detection, showcasing the potential of conductive hydrogels in wearable technology [92].
In soft bioelectronics and sensing, significant strides have been made.High-performance conducting polymer hydrogel-based Electrobiosignal Interfaces (EBIs) have improved ECG and EMG signal recording capabilities [93].The fabrication of self-healable hydrogelliquid metal composites for customizable multimodular sensor systems demonstrates practical advances in self-healing electronics [94].Additionally, the reporting on 3Dprinted implantable hydrogel bioelectronics for precise electrophysiological monitoring and electrical modulation emphasizes the potential in healthcare monitoring and therapies [95].
Furthermore, innovations in sensing and energy generation highlight the versatility of hydrogels.The rapid construction of double-network ionic conductive hydrogel for iontronic pressure sensors with biomimetic fingerprint microstructures enables tactile sensing and human motion detection [96].The development of a 3D-printed conducting polymer hydrogel-based direct current (DC) generator for self-powered electromechanical sensing underlines the robust mechanical properties and flexibility, crucial for wearable electronics and environmental monitoring [97].
These advancements show the potential of conductive hydrogels to transform various industries by providing flexible, durable, and increasingly integrated solutions with electronic functionalities.The progress in this field is a testament to the collaborative efforts of researchers and engineers in pushing the boundaries of material science, electronics, and biomedical engineering (Table 3).

Self-Healing and Responsive Hydrogels
The recent advancements in hydrogel technology, as evidenced by various studies, underscore significant progress in the fields of material science, 3D printing, and responsive actuators.A notable development includes the preparation of self-healing polyacrylamide (PAA)-based hydrogels tailored for extrusion-based 3D printing, which exhibit exceptional self-healing capabilities and rheological properties.This innovation enables the creation of diverse 3D structures that maintain integrity without deformation, enhancing the potential for practical applications [20].Furthermore, improvements in the 3D printing resolution of Digital Light Processing (DLP) for high-water-content hydrogels have been achieved through the use of water-soluble photo-absorbers, which serve to enhance both mechanical properties and biocompatibility [101].Figure 5 below shows a picture of an extrusion-based 3D printer and different views of 3D-printed structures.
The field has also seen the introduction of multi-responsive hydrogel actuators capable of anisotropic swelling, thereby enabling controllable motion.This development highlights the versatility of 3D printing in encoding complex behaviors within materials [102].Similarly, photothermal responsiveness has been integrated into nanocomposite hydrogels, providing a pathway for actuators to exhibit controlled behaviors, thereby widening their application scope [103].The incorporation of aligned graphene oxide (GO) within hydrogels has led to the realization of multi-stimuli-responsive actuation, facilitating complex architectural transformations [104].The field has also seen the introduction of multi-responsive hydrogel actuators capable of anisotropic swelling, thereby enabling controllable motion.This development highlights the versatility of 3D printing in encoding complex behaviors within materials [102].Similarly, photothermal responsiveness has been integrated into nanocomposite hydrogels, providing a pathway for actuators to exhibit controlled behaviors, thereby widening their application scope [103].The incorporation of aligned graphene oxide (GO) within hydrogels has led to the realization of multi-stimuli-responsive actuation, facilitating complex architectural transformations [104].
On the front of innovative applications, there have been significant strides in developing hydrogel-based systems for sensing and soft robotics.A skin-like sensor incorporating a thermo-responsive hydrogel demonstrates temperature and pressure sensitivity, marking an advancement in wearable device applications and artificial intelligence [105].Additionally, bio-hygromorphs that combine fish swim bladder hydrogels with 3D-printed scaffolds exhibit moisture-triggered morphing, presenting new possibilities for actuators and soft robotics [106].The development of photothermal responsive hydrogels capable of ultra-fast and reversible deformation under near-infrared light exposure suggests potential uses in ultra-fast microrobotics for object manipulation [107].
The integration of hydrogels with 3D printing and electrospinning techniques has led to the creation of actuators with rapid response and enhanced designability in threedimensional shapes [108].This approach, along with the development of anisotropic models for hydrogel-fiber composites, enables the design of shape-morphing structures with tailored swelling behaviors [109].The advancements in achieving the complex and controllable shape deformation of hydrogel architectures broaden their applications in soft robotics and tissue engineering [110].
In conclusion, the research and developments in hydrogel technology have led to a broad spectrum of applications ranging from 3D printing, soft robotics, to wearable sensors.These advancements, characterized by innovations in self-healing materials, multi-responsive actuators, and programmable shape transformations, highlight the material's versatility and potential to address various challenges across multiple disciplines (Table 4).On the front of innovative applications, there have been significant strides in developing hydrogel-based systems for sensing and soft robotics.A skin-like sensor incorporating a thermo-responsive hydrogel demonstrates temperature and pressure sensitivity, marking an advancement in wearable device applications and artificial intelligence [105].Additionally, bio-hygromorphs that combine fish swim bladder hydrogels with 3D-printed scaffolds exhibit moisture-triggered morphing, presenting new possibilities for actuators and soft robotics [106].The development of photothermal responsive hydrogels capable of ultra-fast and reversible deformation under near-infrared light exposure suggests potential uses in ultra-fast microrobotics for object manipulation [107].
The integration of hydrogels with 3D printing and electrospinning techniques has led to the creation of actuators with rapid response and enhanced designability in threedimensional shapes [108].This approach, along with the development of anisotropic models for hydrogel-fiber composites, enables the design of shape-morphing structures with tailored swelling behaviors [109].The advancements in achieving the complex and controllable shape deformation of hydrogel architectures broaden their applications in soft robotics and tissue engineering [110].
In conclusion, the research and developments in hydrogel technology have led to a broad spectrum of applications ranging from 3D printing, soft robotics, to wearable sensors.These advancements, characterized by innovations in self-healing materials, multiresponsive actuators, and programmable shape transformations, highlight the material's versatility and potential to address various challenges across multiple disciplines (Table 4).

Osteochondral and Bone Tissue Engineering
Recent advancements in the field of osteochondral and bone tissue engineering have been marked by significant progress in scaffold development, emphasizing the balance between mechanical strength, biodegradability, and biological performance.A pivotal aspect of this progress is the development of high-strength, biohybrid gradient hydrogel scaffolds, which exhibit controllable architecture and mechanical properties, making them suitable for direct 3D printing applications [119].This is complemented by the fabrication of biodegradable supramolecular-polymer-reinforced-gelatin hydrogel scaffolds tailored for osteochondral regeneration, highlighting an emphasis on both enhanced mechanical strength and biological performance [120].Such advancements emphasize the industry's focus on creating supportive environments conducive to tissue repair and regeneration.Figure 6 below shows mechanical testing of pristine PNT-35%-6 hydrogel scaffolds and its TCP biohybrid.
In hydrogel scaffolds, notable innovations include the development of beta-sheetreinforced NP hydrogels, which boast improved mechanical properties and anti-swelling capabilities, beneficial for osteochondral tissue regeneration.These scaffolds facilitate cell support and differentiation, showcasing the potential of bilayer structures in tissue engineering [121].Additionally, hybrid hydrogel scaffolds have been developed for bone tissue engineering, demonstrating improved osteogenesis and cell adhesion capabilities.This highlights the potential of 3D printing technology in creating scaffolds that support complex tissue engineering applications [122].
The application of 3D printing and bioprinting technologies represents a significant trend in tissue engineering, offering innovative solutions for fabricating scaffolds with precise structural and mechanical properties.For instance, the creation of gelatin/HA/3Dgraphene scaffolds with enhanced mechanical properties signals a move towards scaffolds that can better mimic the physical and biological environment of native tissues [123].Furthermore, the adoption of 3D bioprinting for the development of tissue-engineered heart valves demonstrates the versatility of these technologies in producing viable constructs for in vitro testing and potential clinical applications [124].
Novel scaffold designs have been introduced to promote enhanced tissue regeneration, incorporating drug-release mechanisms and bioactive materials to stimulate specific biological responses.Alg/Gel ink containing MBG and ZIF-8 has been used to develop bone scaffolds with drug-release capabilities, aiming to enhance bone regeneration (e.g., [125]).Hybrid scaffolds have also been shown to improve osteogenic and angiogenic performance, offering promising solutions for the regeneration of large bone defects (e.g., [126]).
Furthermore, efforts to improve tissue integration and angiogenesis have yielded significant results, particularly in the context of wound healing and bone regeneration.For example, 3D-printed alginate/gelatin-based scaffolds have demonstrated enhanced tissue integration and angiogenesis, crucial for diabetic wound healing [127].An ECMenriched hydrogel in a 3D-printed scaffold has shown potential in enhancing vascularized bone formation, emphasizing the importance of scaffold design in supporting not only cell growth but also integration with the surrounding tissues and promoting blood vessel formation [128].
In conclusion, the trends in osteochondral and bone tissue engineering reflect a comprehensive approach towards developing scaffolds that support effective tissue regeneration.These developments illustrate a commitment to overcoming the challenges inherent in tissue engineering, aiming to offer innovative solutions for tissue repair and regeneration (Table 5).

Drug Delivery Systems and Therapeutic Applications
The exploration of innovative drug delivery systems and their therapeutic applications has seen significant advancements, focusing on improving treatment efficacy, minimizing side-effects, and enhancing patient compliance through the utilization of novel materials and techniques.Three exemplary developments in this field include fabricated hydrogel scaffolds for cancer therapy, hydrogel contact lenses for the treatment of diabetic retinopathy, and DNA-induced biomineralization techniques for 3D-printed wound dressings.
Fabricated hydrogel scaffolds have been developed for targeted cancer therapy, demonstrating a capacity for controlled drug release directly at the tumor site, which significantly reduces systemic toxicity associated with conventional chemotherapy treatments.This approach not only offers a more personalized and targeted therapy but also aims to enhance the efficacy of postoperative treatment, aligning with the trend towards more patientspecific cancer treatments.The precise control over drug release exemplified by these hydrogel scaffolds represents a significant step forward in the field of oncology, aiming to improve therapeutic outcomes while reducing adverse effects [138].
In ophthalmology, hydrogel contact lenses have been explored as a novel drug delivery system for diabetic retinopathy, a leading cause of blindness globally.This development marks a shift towards non-invasive, accessible treatments, offering a simpler and costeffective alternative to traditional invasive procedures.The use of drug-eluting contact lenses points to a broader trend in healthcare towards improving treatment accessibility and patient compliance, facilitating easier management of chronic conditions such as diabetic retinopathy [139].
Furthermore, the introduction of a DNA-induced biomineralization technique for the creation of 3D-printed wound dressings highlights a significant innovation in wound care, particularly for diabetic wounds.This technique enhances the biological activity of dressings, promoting accelerated healing and reducing infection risks.By leveraging DNA sequences to induce biomineralization, this approach illustrates the convergence of biotechnology and material science, aiming to produce wound care solutions that are not only effective but also biologically active, setting a new standard in the treatment of complex wounds [140].
These developments collectively reflect a broader trend towards leveraging advanced technologies and materials to address specific healthcare challenges, emphasizing the importance of personalized treatment, minimal side-effects, and enhanced patient compliance (Table 6).

Hydrogel Testing and Evaluation
The exploration of 3D-printed hydrogels involves a comprehensive range of testing methods and evaluations, aiming to optimize their utility for varied applications.This analysis highlights the importance of customizing hydrogel properties to meet the specific requirements of diverse fields such as biomedical applications, mechanical enhancements, and responsive functionalities.Through a detailed review, several key trends in testing methodologies emerge, showcasing the interdisciplinary nature of hydrogel research and development.
A pivotal area of focus is on the mechanical properties and structural integrity of hydrogels, with a significant body of work [2,22,23,49,56,57,59,60,62,65,[71][72][73][74]80] emphasizing the evaluation of tensile strength, compressive strength, elasticity, toughness, and viscoelastic properties.This emphasis is crucial for applications where mechanical integrity is paramount, such as tissue engineering scaffolds [119,121,122,129] and soft robotics [63].Various methods, including traditional mechanical testing, rheological measurements [47], and optimization of sintering processes [62], highlight the diverse strategies employed to enhance and assess hydrogel mechanical performance.Ultrasound-based techniques such as macro-indentation [141], multimode ultrasound viscoelastography (MUVE) [142], and dual-mode ultrasound elastography (DUE) [143] provide precise, non-invasive methods to measure the mechanical properties of hydrogels.These methods enable the estimation of elastic moduli, and the characterization of viscoelastic properties with high spatial and temporal resolution.MUVE excels in measuring viscoelastic behavior in soft hydrogels, offering superior sensitivity and resolution compared to traditional methods [142].DUE allows for the non-invasive creep testing of hydrogel biomaterials, providing insights into the material's stiffness and viscoelastic properties [143].Additionally, ultrasound elastography has potential applications in medical diagnostics, such as differentiating between normal uterine tissue and pathological conditions [144].These ultrasound techniques are instrumental in advancing research in mechanobiology and tissue engineering by accurately characterizing the microscale mechanical properties of biomaterials.
Another trend is the focus on biocompatibility and cellular interactions, with numerous studies [9,13,44,45,54,55,58,[83][84][85] investigating cell viability, proliferation, differentiation, and specific biological responses.These assessments are vital for hydrogels intended for regenerative medicine, drug delivery systems, and tissue engineering, where the material's compatibility with biological systems is a key determinant of success.Techniques such as confocal microscopy, cell patterning, and co-culture perfusion [9,10,54] play a crucial role in evaluating the hydrogels' biomedical efficacy.
There is also a concerted effort to optimize the 3D printing process and integrate functional capabilities within hydrogels, as seen in studies [1,4,6,10,11,50,145].This research highlights the importance of refining printing techniques to achieve gradient structures, em-bedded functionalities, and precise architectural control, catering to advanced applications such as microvasculature fabrication [10] and embedded microchannels [6].
The development of responsive or "smart" hydrogels [102][103][104][107][108][109][110][111][112]115,118] represents a forward-thinking trend.These materials are designed to alter their properties in response to external stimuli, targeting applications in actuation, sensing, and controlled drug release.This move towards dynamic, adaptable materials signifies a shift towards hydrogels capable of performing complex, responsive tasks.In hydrogel scaffolds, notable innovations include the development of beta-sheetreinforced NP hydrogels, which boast improved mechanical properties and anti-swelling capabilities, beneficial for osteochondral tissue regeneration.These scaffolds facilitate cell support and differentiation, showcasing the potential of bilayer structures in tissue engineering [121].Additionally, hybrid hydrogel scaffolds have been developed for bone tissue engineering, demonstrating improved osteogenesis and cell adhesion capabilities.This highlights the potential of 3D printing technology in creating scaffolds that support complex tissue engineering applications [122].
The application of 3D printing and bioprinting technologies represents a significant trend in tissue engineering, offering innovative solutions for fabricating scaffolds with precise structural and mechanical properties.For instance, the creation of gelatin/HA/3Dgraphene scaffolds with enhanced mechanical properties signals a move towards scaffolds that can better mimic the physical and biological environment of native tissues [123].Furthermore, the adoption of 3D bioprinting for the development of tissue-engineered heart valves demonstrates the versatility of these technologies in producing viable constructs for in vitro testing and potential clinical applications [124].
Novel scaffold designs have been introduced to promote enhanced tissue regeneration, incorporating drug-release mechanisms and bioactive materials to stimulate specific biological responses.Alg/Gel ink containing MBG and ZIF-8 has been used to develop bone scaffolds with drug-release capabilities, aiming to enhance bone regeneration (e.g., [125]).Hybrid scaffolds have also been shown to improve osteogenic and angiogenic performance, offering promising solutions for the regeneration of large bone defects (e.g., [126]).
Furthermore, efforts to improve tissue integration and angiogenesis have yielded significant results, particularly in the context of wound healing and bone regeneration.For example, 3D-printed alginate/gelatin-based scaffolds have demonstrated enhanced tissue integration and angiogenesis, crucial for diabetic wound healing [127].An ECM- Furthermore, the research on stretchable and conductive hydrogels [17,89,90,[92][93][94][95]97,100] is gaining traction.Evaluations of electrical conductivity, stretchability, self-healing abilities, and gauge factors are critical for applications in wearable electronics, sensors, and bioelectronic interfaces, highlighting the potential of hydrogels that merge mechanical durability with electrical functionality.
In conclusion, the array of testing methodologies applied to 3D-printed hydrogels features the material's adaptability and the broad spectrum of potential applications.From structural and mechanical assessments to biocompatibility evaluations and the integration of functional features, the current trends in testing reflect a concerted, interdisciplinary effort to tailor hydrogel properties to specific needs.As the research in this field continues to evolve, refining these testing methods will play a crucial role in unveiling new applications and enhancing the capabilities of hydrogel-based systems.

Limitations of Using 3D Printed Hydrogels
In the domain of 3D printing technology, materials, and process optimization, hydrogels have faced difficulties in achieving the requisite mechanical properties for specific biomedical applications, such as load-bearing tissue regeneration.This is attributed to their lack of strength and durability [2,5].Efforts to enhance biocompatibility and biofunctionality are ongoing, focusing on the incorporation of cell-signaling molecules and the creation of bioinspired scaffolds [45,54].Despite innovative approaches, such as the development of multi-hydrogel vasculature systems, vascularization remains a critical challenge for the survival and integration of engineered tissues [9].Furthermore, the field grapples with achieving high resolution and fidelity in 3D-printed structures [7,50], compounded by the complexity of regulatory landscapes for clinical applications [7,9,45,50,54].
Optimization efforts towards scaffold mechanical enhancement and biocompatibility have yet to fully succeed in matching the mechanical properties and elasticity of native tissues [23,[56][57][58].The pursuit of universal biocompatibility to promote desired cellular activities continues [14,67,68], alongside engineering scaffolds that support vascularization and integration with host tissues, particularly for complex constructs [58,66].High-resolution printing and regulatory requirements pose significant barriers to clinical adoption [7,50,58,66].
The creation of stretchable and conductive hydrogels, which maintain mechanical flexibility and electrical conductivity under stress, presents its own set of challenges [89,90,92].Further optimization is necessary for their integration with biological tissues for applications in bioelectronics and tissue engineering [91,93].Issues of scalability, reproducibility, self-healing efficiency, degradation rates, and environmental impact remain significant hurdles [21,94,[98][99][100].
For self-healing and responsive hydrogels, ensuring long-term durability under repetitive stress conditions is a challenge [20,102,103].Developing hydrogels that respond rapidly to stimuli requires further optimization [101,104,111].Scalability and the simplification of manufacturing processes, without compromising functionality, are essential for sustainable development, alongside integration with electronic and biomedical systems and addressing environmental stability and degradability [105][106][107]110,112,113,115,117,118].
Finally, in drug delivery systems and therapeutic applications, developing precise and controllable drug release profiles is elusive, necessitating tailored kinetics [138,139].Ensuring long-term biocompatibility, minimizing potential toxicity, and achieving predictable degradation rates are critical for efficacy [138,140].Moreover, the scalability of production and enhancing patient compliance, especially for hydrogel-based devices like contact lenses, are vital for commercial viability and therapeutic effectiveness [139,140].This comprehensive overview highlights the multifaceted challenges in the development of 3D-printed hydrogels, underlining the need for interdisciplinary approaches to overcome these obstacles and advance the field.

Future Directions
The future of 3D-printed hydrogels is poised at the confluence of innovation and optimization, spanning materials, processes, and technologies.

Three-Dimensional Printing Technology, Material, and Process Optimization
The evolution of material innovation is fundamental, emphasizing the development of new hydrogel formulations to precisely emulate target tissues.This includes the integration of smart materials capable of responding to environmental stimuli [55] and fostering cellular activities [13], alongside hybrid approaches that combine Direct Ink Writing with melt electrowriting [47] to improve both resolution and mechanical properties.Computational modeling and design are also highlighted as key for achieving more accurate scaffold designs, leveraging predictive modeling within CAD/CAM tools to align closely with physiological requirements.Furthermore, research focusing on in vivo integration and functionality, such as immune response, degradation, and tissue remodeling [45,54], is deemed critical for the clinical success of printed structures.The development of clear regulatory guidelines and standards is identified as essential for smoothing the regulatory approval pathway.

Scaffold Mechanical Enhancement and Biocompatibility
The field is advancing through novel crosslinking methods [15,18,19] and the incorporation of functional materials [69][70][71], aiming to strike a balance between strength, biocompatibility, and biodegradability.Enhanced bioprinting techniques [74][75][76] and the integration of bioactive molecules [60,72,73] are paving the way for more intricate and functional tissue constructs.The development of smart and responsive hydrogels [77][78][79] heralds new prospects for medical devices and drug delivery systems.Furthermore, the emphasis on customization and patient-specific solutions emphasizes the importance of interdisciplinary collaboration and personalized medicine [84,85,146].

Stretchable and Conductive Hydrogels
Innovations are merging hydrogels with materials like liquid metals [94,100] and conducting polymers [93,95], aiming to surpass current limitations and augment functionality.The development of next-generation implantable devices is being driven by advanced manufacturing techniques [21,89,91] and biohybrid interfaces [93].Additionally, the exploration of smart sensing systems for health monitoring and environmental sensing [96,97] emphasizes the quest for sustainable and biodegradable solutions [99].

Self-Healing and Responsive Hydrogels
The field is moving towards emulating complex biological processes through selfhealing hydrogels [102,103,115] and precision 3D printing techniques [101,110,111].This is complemented by material development inspired by bioinspired design principles [108,113,118], with a focus on sustainable production [106,107].

Osteochondral and Bone Tissue Engineering
The enhancement in tissue regeneration mimicry is being addressed through advanced material combinations and hybrid scaffolds [25,119,121,123,129,137], along with smart hydrogels [102,103,135].Achieving control over scaffold architecture [110,111,122] is essential, as is the conducting of in vivo and clinical studies [126,128,131].

Drug Delivery Systems and Therapeutic Applications
The advancement of targeted therapy is being pursued with smart and responsive hydrogels capable of controlled drug release, integrating nanotechnology [138,140] and advanced fabrication techniques [139,140].Addressing clinical, regulatory, sustainability, and ethical aspects is crucial for the responsible development of these systems [138][139][140].
In conclusion, the progression of 3D-printed hydrogels represents a holistic approach that blends material innovation, fabrication advancements, in vivo functionality, regulatory compliance, and interdisciplinary collaboration.Such concerted efforts are vital for addressing existing challenges and unlocking the extensive potential of hydrogels in various applications.

Conclusions
The advancements in 3D-printed hydrogels have revolutionized various fields, offering solutions to complex challenges in tissue engineering, drug delivery, soft robotics, and beyond.By customizing hydrogels, tissue engineering has seen significant progress, with bio-based scaffolds improving tissue regeneration and microvasculature engineering enhancing functionality.Bioprinting technologies have become more versatile, enabling complex structures and sacrificial techniques for enhanced nutrient transport.In soft robotics, hydrogels have enabled the creation of responsive actuators and environmentally sustainable systems.Drug delivery systems benefit from controlled release mechanisms and personalized treatment options.Despite challenges like mechanical strength and regulatory hurdles, ongoing research aims to optimize materials and processes, ensuring the continued evolution and widespread adoption of 3D-printed hydrogels across diverse applications.

Figure 1 .
Figure 1.Extrusion printing (A) on a surface and (B) within a suspension bath [37].Figure 1. Extrusion printing (A) on a surface and (B) within a suspension bath [37].

Figure 1 .
Figure 1.Extrusion printing (A) on a surface and (B) within a suspension bath [37].Figure 1. Extrusion printing (A) on a surface and (B) within a suspension bath [37].

Figure 2 .
Figure 2. (A) Patient-specific designs from medical scanning images.(B) Biomaterial ink/bioink preparations.(C) The VP printing process in a layer-by-layer manner.(D-F) Exemplary applications of VP-printed constructs in biomedicine [42].

Figure 2 .
Figure 2. (A) Patient-specific designs from medical scanning images.(B) Biomaterial ink/bioink preparations.(C) The VP printing process in a layer-by-layer manner.(D-F) Exemplary applications of VP-printed constructs in biomedicine [42].

Table 1 .
Three-dimensional printing technologies, material, and process optimization.

Table 2 .
Three-dimensional hydrogel compositions for scaffold mechanical enhancement and biocompatibility.

Table 5 .
Three-dimensionally printed hydrogel compositions in osteochondral and bone tissue engineering.

Table 6 .
Three-dimensionally printed hydrogel compositions in drug delivery and therapeutics.