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.

Photothermal therapy (PTT) is a fledgling therapeutic strategy for cancer treatment with minimal invasiveness but clinical adoption has been stifled by concerns such as insufficient biodegradability of the PTT agents and lack of an efficient delivery system. Here, black phosphorus (BP) nanosheets are incorporated with a thermosensitive hydrogel [poly(d,l‐lactide)‐poly(ethylene glycol)‐poly(d,l‐lactide) (PDLLA‐PEG‐PDLLA: PLEL)] to produce a new PTT system for postoperative treatment of cancer. The BP@PLEL hydrogel exhibits excellent near infrared (NIR) photothermal performance and a rapid NIR‐induced sol–gel transition as well as good biodegradability and biocompatibility in vitro and in vivo. Based on these merits, an in vivo PTT postoperative treatment strategy is established. Under NIR irradiation, the sprayed BP@PLEL hydrogel enables rapid gelation forming a gelled membrane on wounds and offers high PTT efficacy to eliminate residual tumor tissues after tumor removal surgery. Furthermore, the good photothermal antibacterial performance prevents infection and this efficient and biodegradable PTT system is very promising in postoperative treatment of cancer.

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.