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.

Biomacromolecules with poor mechanical properties cannot satisfy the stringent requirement for load‐bearing as bioscaffolds. Herein, a biodegradable high‐strength supramolecular polymer strengthened hydrogel composed of cleavable poly( N ‐acryloyl 2‐glycine) (PACG) and methacrylated gelatin (GelMA) (PACG‐GelMA) is successfully constructed by photo‐initiated polymerization. Introducing hydrogen bond‐strengthened PACG contributes to a significant increase in the mechanical strengths of gelatin hydrogel with a high tensile strength (up to 1.1 MPa), outstanding compressive strength (up to 12.4 MPa), large Young's modulus (up to 320 kPa), and high compression modulus (up to 837 kPa). In turn, the GelMA chemical crosslinking could stabilize the temporary PACG network, showing tunable biodegradability by adjusting ACG/GelMA ratios. Further, a biohybrid gradient scaffold consisting of top layer of PACG‐GelMA hydrogel‐Mn 2+ and bottom layer of PACG‐GelMA hydrogel‐bioactive glass is fabricated for repair of osteochondral defects by a 3D printing technique. In vitro biological experiments demonstrate that the biohybrid gradient hydrogel scaffold not only supports cell attachment and spreading but also enhances gene expression of chondrogenic‐related and osteogenic‐related differentiation of human bone marrow stem cells. Around 12 weeks after in vivo implantation, the biohybrid gradient hydrogel scaffold significantly facilitates concurrent regeneration of cartilage and subchondral bone in a rat model.

Although great progress has been made in coaxial extrusion printing toward generating microtubes for mimicking tubular tissues, these microtubes with insufficient mechanical properties and uncontrollable inherent swelling attribute severely hinder their utilization as load-bearing tubular tissue. Herein, a high-strength microtube is constructed by coaxial printing with a customized biohybird hydrogel ink consisting of nanoclay, H-bonding mono mer N-acryloyl glycinamide, and gelatin methacryloyl. The physical interpenetration between nanoclay and polymer chains endows this ink with excellent printability and structural stability, thus facilitating the precise deposition of scalable microtubes with tunable small-diameters and large-scale lengths. After photocrosslinking, 3D-printed biohybrid hydrogel microtube demonstrates marvelous mechanical properties with a tensile strength (≈22 MPa), a stretchability (≈500%), a Young's modulus (≈21 MPa), an anti-fatigue performance (≈200 cycles), a burst pressure (≈2500 mmHg), and a suture retention strength (≈280 gf) in swelling equilibrium state, which are far superior to the previously printed microtubes and generally satisfy the requirements of tubular tissues. Additionally, this obtained microtube also displays favorable biological features that support adhesion, spreading, and endothelialization of human umbilical vein endothelial cells. This study successfully develops a biohybrid hydrogel ink to fabricate a scalable high-strength microtube with enormous potential in regeneration of tube-like tissues.