Direct‐Write Assembly of Microperiodic Silk Fibroin Scaffolds for Tissue Engineering Applications

Three–dimensional, microperiodic scaffolds of regenerated silk fibroin have been fabricated for tissue engineering by direct ink writing. The ink, which consisted of silk fibroin solution from the Bombyx mori silkworm, was deposited in a layer‐by‐layer fashion through a fine nozzle to produce a 3D array of silk fibers of diameter 5 µm. The extruded fibers crystallized when deposited into a methanol‐rich reservoir, retaining a pore structure necessary for media transport. The rheological properties of the silk fibroin solutions were investigated and the crystallized silk fibers were characterized for structure and mechanical properties by infrared spectroscopy and nanoindentation, respectively. The scaffolds supported human bone marrow‐derived mesenchymal stem cell (hMSC) adhesion, and growth. Cells cultured under chondrogenic conditions on these scaffolds supported enhanced chondrogenic differentiation based on increased glucosaminoglycan production compared to standard pellet culture. Our results suggest that 3D silk fibroin scaffolds may find potential application as tissue engineering constructs due to the precise control of their scaffold architecture and their biocompatibility.     

3D Printing of Multifunctional Conductive Polymer Composite Hydrogels

Functional conductive hydrogels are widely used in various application scenarios, such as artificial skin, cell scaffolds, and implantable bioelectronics. However, their novel designs and technological innovations are severely hampered by traditional manufacturing approaches. Direct ink writing (DIW) is considered a viable industrial-production 3D-printing technology for the custom production of hydrogels according to the intended applications. Unfortunately, creating functional conductive hydrogels by DIW has long been plagued by complicated ink formulation and printing processes. In this study, a highly 3D printable poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS)-based ink made from fully commercially accessible raw materials is demonstrated. It is shown that complex structures can be directly printed with this ink and then precisely converted into high-performance hydrogels via a post-printing freeze–thawing treatment. The 3D-printed hydrogel exhibits high electrical conductivity of ≈2000 S m⁻¹, outstanding elasticity, high stability and durability in water, electromagnetic interference shielding, and sensing capabilities. Moreover, the hydrogel is biocompatible, showing great potential for implantable and tissue engineering applications. With significant advantages, the fabrication strategy is expected to open up a new route to create multifunctional hydrogels with custom features, and can bring new opportunities to broaden the applications of hydrogel materials.     

Direct 3D Printed Biomimetic Scaffolds Based on Hydrogel Microparticles for Cell Spheroid Growth

Biocompatible hydrogel inks with shear‐thinning, appropriate yield strength, and fast self‐healing are desired for 3D bioprinting. However, the lack of ideal 3D bioprinting inks with outstanding printability and high structural fidelity, as well as cell‐compatibility, has hindered the progress of extrusion‐based 3D bioprinting for tissue engineering. In this study, novel self‐healable pre‐cross‐linked hydrogel microparticles (pcHμPs) of chitosan methacrylate (CHMA) and polyvinyl alcohol (PVA) hybrid hydrogels are developed and used as bioinks for extrusion‐based 3D printing of scaffolds with high fidelity and biocompatibility. The pcHμPs display excellent shear thinning when injected through a syringe and subsequently self‐heal into gels as shear forces are removed. Numerical simulations indicate that the pcHμPs experience a plug flow in the nozzle with minimal disturbance, which favors a steady and continuous printing. Moreover, the pcHμPs show a self‐supportive yield strength (540 Pa), which is critical for the fidelity of printed constructs. A series of biomimetic constructs with very high aspect ratio and delicate fine structures are directly printed by using the pcHμP ink. The 3D printed scaffolds support the growth of bone‐marrow‐derived mesenchymal stem cells and formation of cell spheroids, which are most important for tissue engineering.     

Direct 3D Printing of High Strength Biohybrid Gradient Hydrogel Scaffolds for Efficient Repair of Osteochondral Defect

The emerging 3D printing technique allows for tailoring hydrogel‐based soft structure tissue scaffolds for individualized therapy of osteochondral defects. However, the weak mechanical strength and uncontrollable swelling intrinsic to conventional hydrogels restrain their use as bioinks. Here, a high‐strength thermoresponsive supramolecular copolymer hydrogel is synthesized by one‐step copolymerization of dual hydrogen bonding monomers, N‐acryloyl glycinamide, and N‐[tris(hydroxymethyl)methyl] acrylamide. The obtained copolymer hydrogels demonstrate excellent mechanical properties—robust tensile strength (up to 0.41 MPa), large stretchability (up to 860%), and high compressive strength (up to 8.4 MPa). The rapid thermoreversible gel ? sol transition behavior makes this copolymer hydrogel suitable for direct 3D printing. Successful preparation of 3D‐printed biohybrid gradient hydrogel scaffolds is demonstrated with controllable 3D architecture, owing to shear thinning property which allows continuous extrusion through a needle and also immediate gelation of fluid upon deposition on the cooled substrate. Furthermore, this biohybrid gradient hydrogel scaffold printed with transforming growth factor beta 1 and β‐tricalciumphosphate on distinct layers facilitates the attachment, spreading, and chondrogenic and osteogenic differentiation of human bone marrow stem cells (hBMSCs) in vitro. The in vivo experiments reveal that the 3D‐printed biohybrid gradient hydrogel scaffolds significantly accelerate simultaneous regeneration of cartilage and subchondral bone in a rat model.     

CelloMOF: Nanocellulose Enabled 3D Printing of Metal–Organic Frameworks

3D printing is recognized as a powerful tool to develop complex geometries for a variety of materials including nanocellulose. Herein, a one‐pot synthesis of 3D printable hydrogel ink containing zeolitic imidazolate frameworks (ZIF‐8) anchored on anionic 2,2,6,6‐tetramethylpiperidine‐1‐oxylradical‐mediated oxidized cellulose nanofibers (TOCNF) is presented. The synthesis approach of ZIF‐8@TOCNF (CelloZIF8) hybrid inks is simple, fast (≈30 min), environmentally friendly, takes place at room temperature, and allows easy encapsulation of guest molecules such as curcumin. Shear thinning properties of the hybrid hydrogel inks facilitate the 3D printing of porous scaffolds with excellent shape fidelity. The scaffolds show pH controlled curcumin release. The synthesis route offers a general approach for metal–organic frameworks (MOF) processing and is successfully applied to other types of MOFs such as MIL‐100 (Fe) and other guest molecules as methylene blue. This study may open new venues for MOFs processing and its large‐scale applications.     

Inverted‐Colloidal‐Crystal Hydrogel Matrices as Three‐Dimensional Cell Scaffolds

Successful engineering of functional tissues requires the development of three‐dimensional (3D) scaffolds that can provide an optimum microenvironment for tissue growth and regeneration. A new class of 3D scaffolds with a high degree of organization and unique topography is fabricated from polyacrylamide hydrogel. The hydrogel matrix is molded by inverted colloidal crystals made from 104 μm poly(methyl methacrylate) spheres. The topography of the scaffold can be described as hexagonally packed 97 μm spherical cavities interconnected by a network of channels. The scale of the long‐range ordering of the cavities exceeds several millimeters. In contrast to analogous material in the bulk, hydrogel shaped as an inverted opal exhibits much higher swelling ratios; its swelling kinetics is an order of magnitude faster as well. The engineered scaffold possesses desirable mechanical and optical properties that can facilitate tissue regeneration while allowing for continuous high‐resolution optical monitoring of cell proliferation and cell–cell interaction within the scaffold. The scaffold biocompatibility as well as cellular growth and infiltration within the scaffold were observed for two distinct human cell lines which were seeded on the scaffold and were tracked microscopically up to a depth of 250 μm within the scaffold for a duration of up to five weeks. Ease of production, a unique 3D structure, biocompatibility, and optical transparency make this new type of hydrogel scaffold suitable for most challenging tasks in tissue engineering.     

Elastomeric Fibrous Hybrid Scaffold Supports In Vitro and In Vivo Tissue Formation

Biomimetic materials with biomechanical properties resembling those of native tissues while providing an environment for cell growth and tissue formation, are vital for tissue engineering (TE). Mechanical anisotropy is an important property of native cardiovascular tissues and directly influences tissue function. This study reports fabrication of anisotropic cell‐seeded constructs while retaining control over the construct's architecture and distribution of cells. Newly synthesized poly‐4‐hydroxybutyrate (P4HB) is fabricated with a dry spinning technique to create anelastomeric fibrous scaffold that allows control of fiber diameter, porosity, and rate ofdegradation. To allow cell and tissue ingrowth, hybrid scaffolds with mesenchymalstem cells (MSCs) encapsulated in a photocrosslinkable hydrogel were developed. Culturing the cellularized scaffolds in a cyclic stretch/flexure bioreactor resulted in tissue formation and confirmed the scaffold's performance under mechanical stimulation. In vivo experiments showed that the hybrid scaffold is capable of withstanding physiological pressures when implanted as a patch in the pulmonary artery. Aligned tissue formation occurred on the scaffold luminal surface without macroscopic thrombus formation. This combination of a novel, anisotropic fibrous scaffold and a tunable native‐like hydrogel for cellular encapsulation promoted formation of 3D tissue and provides a biologically functional composite scaffold for soft‐tissue engineering applications.     

Photocurable 3D Printing of High Toughness and Self-Healing Hydrogels for Customized Wearable Flexible Sensors

Currently, most customized hydrogels can only be processed via extrusion-based 3D printing techniques, which is limited by printing efficiency and resolution. Here, a simple strategy for the rapid fabrication of customized hydrogels using a photocurable 3D printing technique is presented. This technique has been rarely used because the presence of water increases the molecular distance between the polymer chains and reduces the monomer polymerization rate, resulting in the failure of rapid solid-liquid separation during printing. Although adding cross-linkers to printing inks can effectively accelerate 3D cross-linked network formation, chemical cross-linking may result in reduced toughness and self-healing ability of the hydrogel. Therefore, an interpenetrated-network hydrogel based on non-covalent interactions is designed to form physical cross-links, affording fast solid-liquid separation. Poly(acrylic acid (AA)-N-vinyl-2-pyrrolidone (NVP)) and carboxymethyl cellulose (CMC) are cross-linked via Zn²⁺-ligand coordination and hydrogen bonding; the resulting mixed AA-NVP/CMC solution is used as the printing ink. The printed poly(AA-NVP/CMC) hydrogel exhibited high tensile toughness (3.38 MJ m⁻³) and superior self-healing ability (healed stress: 81%; healed strain: 91%). Some objects like manipulator are successfully customized by photocurable 3D printing using hydrogels with high toughness and complex structures. This high-performance hydrogel has great potential for application in flexible wearable sensors.     

Nonmulberry Silk Based Ink for Fabricating Mechanically Robust Cardiac Patches and Endothelialized Myocardium‐on‐a‐Chip Application

Bioprinting holds great promise toward engineering functional cardiac tissue constructs for regenerative medicine and as drug test models. However, it is highly limited by the choice of inks that require maintaining a balance between the structure and functional properties associated with the cardiac tissue. In this regard, a novel and mechanically robust biomaterial‐ink based on nonmulberry silk fibroin protein is developed. The silk‐based ink demonstrates suitable mechanical properties required in terms of elasticity and stiffness (≈40 kPa) for developing clinically relevant cardiac tissue constructs. The ink allows the fabrication of stable anisotropic scaffolds using a dual crosslinking method, which are able to support formation of aligned sarcomeres, high expression of gap junction proteins as connexin‐43, and maintain synchronously beating of cardiomyocytes. The printed constructs are found to be nonimmunogenic in vitro and in vivo. Furthermore, delving into an innovative method for fabricating a vascularized myocardial tissue‐on‐a‐chip, the silk‐based ink is used as supporting hydrogel for encapsulating human induced pluripotent stem cell derived cardiac spheroids (hiPSC‐CSs) and creating perfusable vascularized channels via an embedded bioprinting technique. The ability is confirmed of silk‐based supporting hydrogel toward maturation and viability of hiPSC‐CSs and endothelial cells, and for applications in evaluating drug toxicity.     

3D Particle-Free Printing of Biocompatible Conductive Hydrogel Platforms for Neuron Growth and Electrophysiological Recording

Electrically conductive 3D periodic microscaffolds are fabricated using a particle-free direct ink writing approach for use as neuronal growth and electrophysiological recording platforms. A poly (2-hydroxyethyl methacrylate)/pyrrole ink, followed by chemical in situ polymerization of pyrrole, enables hydrogel printing through nozzles as small as 1 µ m. These conductive hydrogels can pattern complex 2D and 3D structures and have good biocompatibility with test cell cultures ( ≈ 94.5% viability after 7 days). Hydrogel arrays promote extensive neurite outgrowth of cultured Aplysia californica pedal ganglion neurons. This platform allows extracellular electrophysiological recording of steady-state and stimulated electrical neuronal activities. In summation, this 3D conductive ink printing process enables the preparation of biocompatible and micron-sized structures to create customized in vitro electrophysiological recording platforms.     

3D Printed Stem‐Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds

A bioengineered spinal cord is fabricated via extrusion‐based multimaterial 3D bioprinting, in which clusters of induced pluripotent stem cell (iPSC)‐derived spinal neuronal progenitor cells (sNPCs) and oligodendrocyte progenitor cells (OPCs) are placed in precise positions within 3D printed biocompatible scaffolds during assembly. The location of a cluster of cells, of a single type or multiple types, is controlled using a point‐dispensing printing method with a 200 µm center‐to‐center spacing within 150 µm wide channels. The bioprinted sNPCs differentiate and extend axons throughout microscale scaffold channels, and the activity of these neuronal networks is confirmed by physiological spontaneous calcium flux studies. Successful bioprinting of OPCs in combination with sNPCs demonstrates a multicellular neural tissue engineering approach, where the ability to direct the patterning and combination of transplanted neuronal and glial cells can be beneficial in rebuilding functional axonal connections across areas of central nervous system (CNS) tissue damage. This platform can be used to prepare novel biomimetic, hydrogel‐based scaffolds modeling complex CNS tissue architecture in vitro and harnessed to develop new clinical approaches to treat neurological diseases, including spinal cord injury.     

3D Fluorescent Hydrogel Origami for Multistage Data Security Protection

Current fluorescence‐based anti‐counterfeiting strategies primarily encode information onto single 2D planes and underutilize the possibility of encrypting data inside 3D structures to achieve multistage data security. Herein, a fluorescent‐hydrogel‐based 3D anti‐counterfeiting platform is demonstrated, which extends data encryption capability from single 2D planes to complex 3D hydrogel origami geometries. The materials are based on perylene‐tetracarboxylic‐acid‐functionalized gelatin/poly(vinyl alcohol) hydrogels, which simultaneously show Fe³⁺‐responsive fluorescence quenching, borax‐triggered shape memory, and self‐healing properties. By employing an origami technique, various complex 3D hydrogel geometries are facilely fabricated. On the basis of these results, a 3D anti‐counterfeiting platform is demonstrated, in which the data printed by using Fe³⁺ as the ink are safely protected inside complex 3D hydrogel origami structures. In this way, the encrypted data cannot be read until after specially predesigned procedures (both the shape recovery and UV light illumination actions), indicating higher‐level information security than the traditional 2D counterparts. This facile and general strategy opens up the possibility of utilizing 3D fluorescent hydrogel origami for data information encryption and protection.     

Electrospun Photocrosslinkable Hydrogel Fibrous Scaffolds for Rapid In Vivo Vascularized Skin Flap Regeneration

Distal necrosis of random skin flap is always clinical problematic in plastic surgery. The development of 3D functional vascular networks is fundamental for the survival of a local random skin flap. Herein, an effective technique on constructing 3D fibrous scaffolds for accelerated vascularization is demonstrated using a photocrosslinkable natural hydrogel based on gelatin methacryloyl (GelMA) by electrospinning. It is found that the ultraviolet (UV) photocrosslinkable gelatin electrospun hydrogel fibrous membranes exhibit soft adjustable mechanical properties and controllable degradation properties. Furthermore, it is observed that the optimized hydrogel scaffolds can support endothelial cells and dermal fibroblasts adhesion, proliferation, and migration into the scaffolds, which facilitates vascularization. Importantly, a rapid formation of tubes is observed after 3 d seeding of endothelial cells. After GelMA fibrous scaffold implantation below the skin flap in a rat model, it is found that the flap survival rate is higher than the control group, and there is more microvascular formation, which is potentially beneficial for the flap tissue vascularization. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.     

Injectable 3D-Printed Porous Scaffolds for Adipose Stem Cell Delivery and Endometrial Regeneration

Stem-cell-based therapeutic strategies are promising in the clinical treatment of intrauterine adhesions (IUAs), while endometrial regeneration still hardly restores the structure and function of the endometrium because of the inadequate microenvironment for the grafted stem cells and subsequent limited therapeutic efficiency. Herein, an injectable porous hydrogel scaffold (PH scaffold) with customizable shapes is presented by using a microfluidic-based 3D printing technique for adipose-derived stem cells (ADSCs) delivery to enhance endometrial regeneration. These scaffolds display a controllable interconnected porous structure, which not only facilitates the encapsulation of ADSCs within the scaffold but also supports the recovery to their original shapes after injection. Furthermore, the cell viability of the laden ADSCs is well-maintained post-injection, exhibiting promotive effects on cell migration, proliferation, and tube formation. Based on these features, an ADSCs-laden PH scaffold with a hollow endometrium-mimicking morphology is designed and in situ injected into the damaged endometrium in rats of IUAs. These results show that the ADSCs-laden PH scaffolds can enhance functional endometrial regeneration by suppressing the inflammatory response, promoting cell proliferation, and improving vascularization. Thus, it is believed that such unique 3D-printed porous scaffolds are promising candidates for cell delivery, which also provides a minimally-invasive and effective strategy for endometrial regeneration.     

Black‐Phosphorus‐Incorporated Hydrogel as a Conductive and Biodegradable Platform for Enhancement of the Neural Differentiation of Mesenchymal Stem Cells

Conductive hydrogel scaffolds have important applications for electroactive tissue repairs. However, the development of conductive hydrogel scaffolds tends to incorporate nonbiodegradable conductive nanomaterials that will remain in the human body as foreign matters. Herein, a biodegradable conductive hybrid hydrogel is demonstrated based on the integration of black phosphorus (BP) nanosheets into the hydrogel matrix. To address the challenge of applying BP nanosheets in tissue engineering due to its intrinsic instability, a polydopamine (PDA) modification method is developed to improve the stability. Moreover, PDA modification also enhances interfacial bonding between pristine BP nanosheets and the hydrogel matrix. The incorporation of polydopamine‐modified black phosphorous (BP@PDA) nanosheets into the gelatin methacryloyl (GelMA) hydrogels significantly enhances the electrical conductivity of the hydrogels and improves the cell migration of mesenchymal stem cells (MSCs) within the 3D scaffolds. On the basis of the gene expression and protein level assessments, the BP@PDA‐incorporated GelMA scaffold can significantly promote the differentiation of MSCs into neural‐like cells under the synergistic electrical stimulation. This strategy of integrating biodegradable conductive BP nanomaterials within a biocompatible hydrogel provides a new insight into the design of biomaterials for broad applications in tissue engineering of electroactive tissues, such as neural, cardiac, and skeletal muscle tissues.     

Designing Microgels for Cell Culture and Controlled Assembly of Tissue Microenvironments

Micrometer‐sized hydrogels, termed microgels, are emerging as multifunctional platforms that can recapitulate tissue heterogeneity in engineered cell microenvironments. The microgels can function as either individual cell culture units or can be assembled into larger scaffolds. In this manner, individual microgels can be customized for single or multicell coculture applications, or heterogeneous populations can be used as building blocks to create microporous assembled scaffolds that more closely mimic tissue heterogeneities. The inherent versatility of these materials allows user‐defined control of the microenvironments, from the order of singly encapsulated cells to entire 3D cell scaffolds. These hydrogel scaffolds are promising for moving towards personalized medicine approaches and recapitulating the multifaceted microenvironments that exist in vivo.     

3D Printing of Multifunctional Hydrogels

3D printing technology has been widely explored for the rapid design and fabrication of hydrogels, as required by complicated soft structures and devices. Here, a new 3D printing method is presented based on the rheology modifier of Carbomer for direct ink writing of various functional hydrogels. Carbomer is shown to be highly efficient in providing ideal rheological behaviors for multifunctional hydrogel inks, including double network hydrogels, magnetic hydrogels, temperature‐sensitive hydrogels, and biogels, with a low dosage (at least 0.5% w/v) recorded. Besides the excellent printing performance, mechanical behaviors, and biocompatibility, the 3D printed multifunctional hydrogels enable various soft devices, including loadable webs, soft robots, 4D printed leaves, and hydrogel Petri dishes. Moreover, with its unprecedented capability, the Carbomer‐based 3D printing method opens new avenues for bioprinting manufacturing and integrated hydrogel devices.     

Integration of a Chemical‐Responsive Hydrogel into a Porous Silicon Photonic Sensor for Visual Colorimetric Readout

The incorporation of a chemo‐responsive hydrogel into a 1D photonic porous silicon (PSi) transducer is demonstrated. A versatile hydrogel backbone is designed via the synthesis of an amine‐functionalized polyacrylamide copolymer where further amine‐specific biochemical reactions can enable control of cross‐links between copolymer chains based on complementary target–probe systems. As an initial demonstration, the incorporation of disulfide chemistry to control cross‐linking of this hydrogel system within a PSi Bragg mirror sensor is reported. Direct optical monitoring of a characteristic peak in the white light reflectivity spectrum of the incorporated PSi Bragg mirror facilitates real‐time detection of the hydrogel dissolution in response to the target analyte (reducing agent) over a timescale of minutes. The hybrid sensor response characteristics are shown to systematically depend on hydrogel cross‐linking density and applied target analyte concentration. Additionally, effects due to responsive hydrogel confinement in a porous template are shown to depend on pore size and architecture of the PSi transducer substrate. Sufficient copolymer and water is removed from the PSi transducer upon dissolution and drying of the hydrogel to induce color changes that can be detected by the unaided eye. This highlights the potential for future development for point‐of‐care diagnostic biosensing.     

3D Printing of Bioinspired Alginate-Albumin Based Instant Gel Ink with Electroconductivity and Its Expansion to Direct Four-Axis Printing of Hollow Porous Tubular Constructs without Supporting Materials

A successful 3D printable hydrogel ink needs not only biofunctionalities but also minimal fabrication steps such as multiple crosslinking sites, high printability, cytocompatibility, high shape fidelity, stability, shear thinning, robust properties, and less time-consuming processing steps, by maximizing known material chemistries and functionalities. This work reports a novel bioinspired conjugate with polysaccharide (alginate)–tannic acid (TA)–protein (bovine serum albumin) to fabricate proteoglycan-like gels, which are 3D printable with multilayers, shear-thinning, elastic, electroconductive (with carbon nanotubes), controlled crosslinking/degradation through multiple crosslinking mechanisms (TA, Ca²⁺ ions, and NaIO₄ oxidation), and interactions with cytocompatible hydrogel system. The synthesis process is simple, and gelation (within 2 h) is ensured without any chemical crosslinking agents (at room temperature). While cell-adhesive albumin largely improves cytocompatibility, carbon nanotubes in the gel give electrical conductivity in the different four-axis 3D printed structures, including large hollow tubular constructs. This work demonstrates promising results of electroconductive proteoglycan-like gel ink to address the challenges in 3D/four-axis ink printing such as synthesis, printability, shape fidelity, electroconductivity, controlled fabrication and degradation, cytocompatibility, and multiple crosslinking abilities to maintain the dimensions of the diversely printed constructs.     

A Self-Thickening and Self-Strengthening Strategy for 3D Printing High-Strength and Antiswelling Supramolecular Polymer Hydrogels as Meniscus Substitutes

3D printing of high-strength and antiswelling hydrogel-based load-bearing soft tissue scaffolds with similar geometric shape to natural tissues remains a great challenge owing to insurmountable trade-off between strength and printability. Herein, capitalizing on the concentration-dependent H-bonding-strengthened mechanism of supramolecular poly(N-acryloyl glycinamide) (PNAGA) hydrogel, a self-thickening and self-strengthening strategy, that is, loading the concentrated NAGA monomer into the thermoreversible low-strength PNAGA hydrogel is proposed to directly 3D printing latently H-bonding-reinforced hydrogels. The low-strength PNAGA serves to thicken the concentrated NAGA monomer, affording an appropriate viscosity for thermal-assisted extrusion 3D printing of soft PNAGA hydrogels bearing NAGA monomer and initiator, which are further polymerized to eventually generate high-strength and antiswelling hydrogels, due to the reconstruction of strong H-bonding interactions from postcompensatory PNAGA. Diverse polymer hydrogels can be printed with self-thickened corresponding monomer inks. Further, the self-thickened high-strength PNAGA hydrogel is printed into a meniscus, which is implanted in rabbit's knee as a substitute with in vivo outcome showing an appealing ability to efficiently alleviate the cartilage surface wear. The self-thickening strategy is applicable to directly printing a variety of polymer-hydrogel-based tissue engineering scaffolds without sacrificing mechanical strength, thus circumventing problems of printing high-strength hydrogels and facilitating their application scope.