Covalent organic frameworks (COFs) as drug delivery systems have shown great promise, but their pharmaceutical applications are often limited by complex building blocks, tedious preparations, irregular shape, and uncontrolled drug release within target cells. Herein, a facile strategy is developed to prepare PEGylated redox‐responsive nanoscale COFs (denoted F68@SS‐COFs) for efficiently loading and delivering doxorubicin (DOX) by use of FDA‐approved Pluronic F68 and commercially available building blocks. The obtained F68@SS‐COFs with controlled size, high stability, and good biocompatibility can not only achieve a very high DOX‐loading content (about 21%) and very low premature leakage at physiological condition but can also rapidly respond to the tumor intracellular microenvironment and efficiently release DOX to kill tumor cells. Considering the readily available raw materials, simple preparation process, and desirable redox‐responsiveness, the strategy provided here opens up a promising avenue to develop well‐defined COFs‐based nanomedicines for cancer therapy.

Rationale: Although a few injectable hydrogels have shown a reliable biosafety and a moderate promise in treating myocardial infarction (MI), the updated hydrogel systems with an on-demand biodegradation and multi-biofunctions to deliver therapeutic drug would achieve more prominent efficacy in the future applications. In this report, a conductive and injectable hydrogel crosslinked by matrix metalloproteinase-sensitive peptides (MMP-SP) was rationally constructed to stabilize hypoxia-inducible factor-1α (HIF-1α) to recover heart functions after MI. Methods: Firstly, tetraaniline (TA) was incorporated into partially oxidized alginate (ALG-CHO) to endow the hydrogels with conductivity. The 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (DPCA) nanodrug was manufactured with high drug loading capacity and decorated with polymerized dopamine (PDA) to achieve a stable release of the drug. Both ALG-CHO and DPCA@PDA can be cross-linked by thiolated hyaluronic acid (HA-SH) and thiolated MMP-SP to construct a MMP-degradable and conductive hydrogel. After administration in the infarcted heart of rats, echocardiographic assessments, histological evaluation, and RT-PCR were used to evaluate therapeutic effects of hydrogels. Results: The cell viability and the results of subcutaneous implantation verify a good cytocompatibility and biocompatibility of the resulting hydrogels. The hydrogel shows remarkable strength in decreasing the expression of inflammatory factors, maintaining a high level of HIF-1α to promote the vascularization, and promoting the expression of junctional protein connexin 43. Meanwhile, the multifunctional hydrogels greatly reduce the infarcted area (by 33.8%) and improve cardiac functions dramatically with ejection fraction (EF) and fractional shortening (FS) being increased by 31.3% and 19.0%, respectively. Conclusion: The as-prepared hydrogels in this report achieve a favorable therapeutic effect, offering a promising therapeutic strategy for treating heart injury.

The self‐healable hydrogels have attracted increasing attention due to their promising potential for ensuring the durability and reliability of hydrogels. However, they still face a serious challenge to achieve a positive balance between mechanical and healing performance, especially for the room‐temperature autonomous self‐healable hydrogels. Herein, a simple but efficient strategy to fabricate a kind of dynamic boronate and hydrogen bonds dual‐crosslinked double network (DN) hydrogel based on a UV‐initiated one‐pot in situ polymerization of N‐acryloyl glycinamide (NAGA) in polyvinyl alcohol‐borax slime is reported. The obtained PN‐x/PB hydrogels, especially with high content of PNAGA, are shown to possess high mechanical strength, high toughness, and fatigue‐resistance properties as well as excellent self‐healability at room temperature (nearly 88% self‐healing efficiency based on the strain compression test), due to the dynamic DN structure, and the combination of the adaptable and reconfigurable dynamic boronate bonds and hydrogen bonds. Considering the easily available materials and simple preparation process, this novel strategy should offer not only a kind of dynamic DN hydrogel with robust mechanical performance and high self‐healing capability, but also enrich the methodological toolbox for synergistic integration of dynamic covalent bonds and hydrogen bonds to surmount the tradeoff between mechanical properties and self‐healing capacity of hydrogels.

The double network (DN) hydrogels, especially the physically crosslinked DN hydrogels, have attracted increasing attention due to their high reconfigurability, multi‐sensitivity, and efficient energy dissipation, but their applications still suffer from the relatively low mechanical strength, complex preparation process, and insufficient functionality. In this work, a simple but efficient strategy to fabricate robust and multitasking polyvinyl alcohol (PVA)/poly(N‐acryloyl glycinamide) (PNAGA) DN hydrogels via an ultraviolet (UV)‐initiated one‐pot in situ polymerization and a subsequent freezing‐thawing treatment is reported. The PVA/PNAGA DN hydrogels are fully physically linked DN network via multiple hydrogen bonding interactions, which contain hard PVA crystalline microdomains and soft PNAGA regions. The synergetic multiple hydrogen bonding interactions and the cooperation of hard and soft regions in PVA/PNAGA hydrogels as well as the polyhydroxy matrix can not only impart the PVA/PNAGA hydrogels with super mechanical strength, high toughness, good stretchability, and rapid shape‐recoverability, but also endow the hydrogels with tailorable self‐healability, multiple shape memory, and actuation function. Considering the easily available materials, simple preparation process, and highly multitasking properties, this novel strategy should greatly enrich the methodological toolbox for the synthesis of robust and multifunctional hydrogels for the diversity of applications.

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