Hydrogels are soft materials used in an array of biomedical applications. However, the in situ formation of hydrogels at target sites, particularly in dynamic in vivo environments, usually requires a prolonged gelation time and results in poor adhesion. These limitations cause considerable loss of both hydrogel mass and encapsulated therapeutic cargoes, thereby compromising treatment outcomes. Here, we report the development of a hydrogel based on thiourea-catechol reaction to enhance the bioadhesion. Compared with classical bioadhesive hydrogels, our hydrogels show enhanced mechanical properties, exceedingly short curing time, and pH-independent gelation with a much lower oxidant concentration. We further report the robust adhesion of our hydrogels to acidic gastric tissues and easy delivery to the porcine stomach via endoscopy. The delivered hydrogels adhered to ulcer sites in vivo for at least 48 hours. Hydrogel treatment of gastric ulcers in rodent and porcine models accelerated ulcer healing by suppressing inflammation and promoting re-epithelization and angiogenesis. The improved retention of proregenerative growth factors and reduced exposure to external catabolic factors after hydrogel application may contribute to the observed therapeutic outcomes. Our findings reveal a promising biomaterial-based approach for treating gastrointestinal diseases.

Achieving strong adhesion of bioadhesives on wet tissues remains a challenge and an acute clinical demand because of the interfering interfacial water and limited adhesive-tissue interactions. Here we report a self-gelling and adhesive polyethyleneimine and polyacrylic acid (PEI/PAA) powder, which can absorb interfacial water to form a physically cross-linked hydrogel in situ within 2 seconds due to strong physical interactions between the polymers. Furthermore, the physically cross-linked polymers can diffuse into the substrate polymeric network to enhance wet adhesion. Superficial deposition of PEI/PAA powder can effectively seal damaged porcine stomach and intestine despite excessive mechanical challenges and tissue surface irregularities. We further demonstrate PEI/PAA powder as an effective sealant to enhance the treatment outcomes of gastric perforation in a rat model. The strong wet adhesion, excellent cytocompatibility, adaptability to fit complex sites, and easy synthesis of PEI/PAA powder make it a promising bioadhesive for numerous biomedical applications.

Abstract3D culture of cells in designer biomaterial matrices provides a biomimetic cellular microenvironment and can yield critical insights into cellular behaviours not available from conventional 2D cultures. Hydrogels with dynamic properties, achieved by incorporating either degradable structural components or reversible dynamic crosslinks, enable efficient cell adaptation of the matrix and support associated cellular functions. Herein we demonstrate that given similar equilibrium binding constants, hydrogels containing dynamic crosslinks with a large dissociation rate constant enable cell force-induced network reorganization, which results in rapid stellate spreading, assembly, mechanosensing, and differentiation of encapsulated stem cells when compared to similar hydrogels containing dynamic crosslinks with a low dissociation rate constant. Furthermore, the static and precise conjugation of cell adhesive ligands to the hydrogel subnetwork connected by such fast-dissociating crosslinks is also required for ultra-rapid stellate spreading (within 18 h post-encapsulation) and enhanced mechanosensing of stem cells in 3D. This work reveals the correlation between microscopic cell behaviours and the molecular level binding kinetics in hydrogel networks. Our findings provide valuable guidance to the design and evaluation of supramolecular biomaterials with cell-adaptable properties for studying cells in 3D cultures.

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Photoacoustic (PA) imaging and tracking of stem cells plays an important role in the real-time assessment of cell-based therapies. Nevertheless, the limitations of conventional inorganic PA contrast agents and the narrow range of the excitation wavelength in the first near-infrared (NIR-I) window hamper the applications of PA imaging in living subjects. Herein, we report the design and synthesis of a second near-infrared (NIR-II) absorptive organic semiconducting polymer (OSP)-based nanoprobe (OSPN+) for PA imaging and tracking of stem cells. Comparison studies in biological tissue show that NIR-II light excited PA imaging of the OSPN+ has significantly higher signal-to-noise ratio than NIR-I light excited PA imaging, thereby demonstrating the superiority of the OSPN+ for deep tissue imaging. With good biocompatibility, appropriate size, and optimized surface property, the OSPN+ shows enhanced cellular uptake for highly efficient PA labeling of stem cells. In vivo investigations reveal significant NIR-II PA contrast enhancement of the transplanted OSPN+-labeled human mesenchymal stem cells by 40.6- and 21.7-fold in subcutaneous and brain imaging, respectively, compared with unlabeled cases. Our work demonstrates a class of OSP-based nanomaterials for NIR-II PA stem cell imaging to facilitate a better understanding and evaluation of stem cell-based therapies.