The self-healing hydrogels are extremely attractive in biological and biomedical fields. The imine bond obtained by the Schiff base reaction is a commonly used dynamic covalent bond to fabricate self-healing hydrogels. Gelatin is a commonly used natural macromolecule in the biomedical field with excellent biocompatibility, biodegradability, and nonimmunogenicity. However, the gelatin-based hydrogels with self-healing ability are rarely reported based on imine bonds. Herein, we present a facile approach to fabricate a gelatin hydrogel with self-healing ability based on the Schiff base reaction. The gelatin was first reacted with ethylenediamine to increase the content of amino groups. Then dialdehyde carboxymethyl cellulose was used to cross-link amino-gelatin to fabricate the self-healing hydrogel. The results showed that the fabricated hydrogel exhibited good self-healing ability as expected because of the formed dynamic imine bonds between amino-gelatin and dialdehyde carboxymethyl cellulose. The hydrogel also presented good fatigue resistance and self-recovery capacity. Moreover, the self-healing hydrogel possessed ideal hemocompatibility and cytocompatibility. In sum, the fabricated self-healing hydrogel has application prospects in biomedical fields, such as injectable cell and drug carrier and injectable tissue engineering scaffold.
Development of alternatives to antibiotics is one of the top priorities in the battle against multidrug-resistant (MDR) bacterial infections. Here, we report that two naturally occurring nonantibiotic modalities, blue light and phytochemical carvacrol, synergistically kill an array of bacteria including their planktonic forms, mature biofilms, and persisters, irrespective of their antibiotic susceptibility. Combination but not single treatment completely or substantially cured acute and established biofilm-associated Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus infections of full thickness murine third-degree burn wounds and rescued mice from lethal Pseudomonas aeruginosa skin wound infections. The combined therapy diminished bacterial colony-forming units as high as 7.5 log10 within 30 min and introduced few adverse events in the survival of cocultured mammalian cells, wound healing, or host DNA. Mechanistic studies revealed that carvacrol was photocatalytically oxidized into a series of photoreactive substrates that underwent photolysis or additional photosensitization reactions in response to the same blue light, forming two autoxidation cycles that interacted with each other resulting in robust generation of cytotoxic reactive oxygen species. This phototoxic reaction took place exclusively in bacteria, initiated by blue light excitation of endogenous porphyrin-like molecules abundantly produced in bacteria compared with mammalian cells. Moreover, no bacterial resistance developed to the combined treatment after 20 successive passages. This highly selective phototoxic reaction confers a unique strategy to combat the growing threat of MDR bacteria.
The complex biological environments and multiple physiological barriers significantly impede efficient accumulation and penetration of nanomaterials within tumor tissue for therapy. In situ energy conversion of nanomotors features autonomous movements and improves cancer treatment. However, one of the key challenges is to prepare nanomotors with an adequately small size, good biocompatibility and precise positioning.Here, we demonstrate a simple, ultra-small, versatile, and real-time motion guidance strategy for magnetocatalytic CoPt@graphene navigators (MCGNs) that can enable highly efficient propulsion in the presence of H 2 O 2 or magnetic actuation. MCGNs act as highly diffusive delivery vehicles to promote tumor tissue targeting, and the amount of drug in the tumor was 3 times than without navigation. By engaging movements powered through in situ energy conversion, MCGNs gain considerable propulsion to penetrate a cell's membrane and enhance intracellular delivery.
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