Both myocardial infarction (MI) and the follow-up reperfusion will lead to an inevitable injury to myocardial tissues, such as cardiac dysfunctions, fibrosis, and reduction of intercellular cell-to-cell interactions. Recently, exosomes (Exo) derived from stem cells have demonstrated a robust capability to promote angiogenesis and tissue repair. However, the short half-life of Exo and rapid clearance lead to insufficient therapeutic doses in the lesion area. Herein, an injectable conductive hydrogel is constructed to bind Exo derived from human umbilical cord mesenchymal stem cells to treat myocardial injuries after myocardial infarction–ischemia/reperfusion (MI-I/R). To this end, a hyperbranched epoxy macromer (EHBPE) grafted by an aniline tetramer (AT) was synthesized to cross-link thiolated hyaluronic acid (HA-SH) and thiolated Exo anchoring a CP05 peptide via an epoxy/thiol “click” reaction. The resulting Gel@Exo composite system possesses multiple features, such as controllable gelation kinetics, shear-thinning injectability, conductivity matching the native myocardium, soft and dynamic stability adapting to heartbeats, and excellent cytocompatibility. After being injected into injured hearts of rats, the hydrogel effectively prolongs the retention of Exo in the ischemic myocardium. The cardiac functions have been considerably improved by Gel@Exo administration, as indicated by the enhancing ejection fraction and fractional shortening, and reducing fibrosis area. Immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) results demonstrate that the expression of cardiac-related proteins (Cx43, Ki67, CD31, and α-SMA) and genes (VEGF-A, VEGF-B, vWF, TGF-β1, MMP-9, and Serca2a) are remarkably upregulated. The conductive Gel@Exo system can significantly improve cell-to-cell interactions, promote cell proliferation and angiogenesis, and result in a prominent therapeutic effect on MI-I/R, providing a promising therapeutic method for injured myocardial tissues.

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Development of a biostable and biosafe vitreous substitute is highly desirable, but remains a grand challenge. Herein, we propose a novel strategy for constructing a readily administered vitreous substitute based on a thiol-acrylate clickable polyzwitterion macromonomer. A biocompatible multivinyl polycarboxybetaine (PCB-OAA) macromonomer is designed and synthesized, and mixed with dithiothreitol (DTT) via a Michael addition reaction to form a hydrogel in vitreous cavity. This resultant PCB-OAA hydrogel exhibits controllable gelation time, super anti-fouling ability against proteins and cells, excellent biocompatibility, and approximate key parameters to human vitreous body including equilibrium water content, density, optical properties, modulus. Remarkably, outperforming clinically used silicone oil in biocompatibility, this rapidly formed hydrogel in the vitreous cavity of rabbit eyes remains stable in vitreous cavity, showing an appealing ability to prevent significantly inflammatory response, fibrosis and complications such as raised intraocular pressure (IOP), and cataract formation. This zwitterionic polymer hydrogel holds great potential as a vitreous substitute.

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