Journal
BIOMACROMOLECULES
Volume 21, Issue 6, Pages 2409-2420Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.0c00347
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Funding
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Canada Foundation for Innovation (CFI)
- Alberta Innovates
- Canada Research Chairs Program
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Injectable, self-healing, and pH-responsive hydrogels are great intelligent drug delivery systems for controlled and localized therapeutic release. Hydrogels that show pH-sensitive behaviors in the mildly acidic range are ideal to be used for the treatment of regions showing local acidosis like tumors, wounds and infections. In this work, we present a facile preparation of an injectable, self-healing, and supersensitive pH-responsive nanocomposite hydrogel based on Schiff base reactions between aldehyde-functionalized polymers and amine-modified silica nano-particles. The hydrogel shows fast gelation within 10 s, injectability, and rapid self-healing capability. Moreover, the hydrogel demonstrates excellent stability under neutral physiological conditions, while a sharp gel-sol transition is observed, induced by a faintly acidic environment, which is desirable for controlled drug delivery. The pH-responsiveness of the hydrogel is ultrasensitive, where the mechanical properties, hydrolytic degradation, and drug release behaviors can alter significantly when subjected to a slight pH change of 0.2. Additionally, the hydrogel's mechanical and pH-responsive properties can be readily tuned by its composition. Its excellent biocompatibility is confirmed by cytotoxicity tests toward human dermal fibroblast cells (HDFa). The novel injectable, self-healing, and sensitive pH-responsive hydrogel serves as a promising candidate as a localized drug carrier with controlled delivery capability, triggered by acidosis, holding great promise for cancer therapy, wound healing, and infection treatment.
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