Multi-stimuli-responsive degradable boronic ester-crosslinked e-spun nanofiber wound dressings†

Owing to their high aspect ratio of length to diameter, large surface area, large pore size, and high molecular orientation, electro-spun (e-spun) nanofibrous mats have been explored as effective nanomaterials for various applications, including wound dressings and healing materials. Of particular interest are poly(vinyl alcohol) (PVA) e-spun nanofibers that are required to be crosslinked with covalent organic bonds to retain their structural integrity in wound environments. However, conventionally crosslinked PVA nanofibers present critical drawbacks, typically including the uncontrolled release of encapsulated drug molecules. Herein, we report a robust approach that centers on the integration of boronic ester (BE) chemistry into the design of PVA e-spun nanofibers crosslinked through the formation of degradable BE crosslinks. A new phenyldiboronic acid with an ethylene spacer, which is biocompatible and has a lower pK_a value, is proved to be an effective crosslinker to fabricate BE-crosslinked PVA e-spun nanofibrous materials. In response to multiple stimuli such as reactive oxygen species, alkaline pH, and glucose (common features of wounds), the fibers degrade through the cleavage of BE bonds or transesterification, confirmed by our model spectroscopic study with a small molecular boronic ester. Such wound-induced degradation ensures the controlled/enhanced release of antibiotics active against both Gram-positive and Gram-negative bacteria. These results, combined with their non-hemolysis and non-cytotoxicity properties, demonstrate that the approach is versatile for the fabrication of well-defined BE-crosslinked PVA e-spun nanofibers that are dimensionally stable but degrade to release antibiotics in wounds, thus exhibiting a great promise as smart wound dressing materials.