Protein-polysaccharide based nanogel/hydrogel composite with controlled continuous delivery of drug for enhanced wound healing

In the development of drug delivery vehicles for full-thickness skin wounds, achieving a specific drug concentration at the active site remains a key challenge. In this work, we reported a novel protein-polysaccharide bio-based composite hydrogel (SG@CRG) with controlled continuous drug delivery for enhanced wound healing. This composite hydrogel was prepared by incorporating drug embedded spirulina protein isolate nanogels (SG) into carboxymethyl chitosan based hydrogel (CRG) network, which exhibited rapid gelation and excellent mechanical properties. Notably, the release rate of the embedded drug could be tuned by adjusting the proportion of SG within the composite hydrogels. In vitro experiments demonstrated that the composite hydrogel exhibited excellent antibacterial activity against both gram-positive and gram-negative bacteria (inhibition rates at 12 h for S. aureus and E. coli were 99.77 % and 98.64 %, respectively), and good biocompatibility. Additionally, the hydrogel could effectively alleviate excessive inflammation and oxidative stress damage. Lastly, a full-thickness mouse skin model was established to assess its wound healing performance in vivo, which found that the composite hydrogel markedly accelerated wound healing (the healing ratios achieved by day 7 and day 12 were 78.37 % and 99.13 %, respectively, compared to 56.99 % and 84.50 % in the control group) by diminishing inflammation, promoting granulation tissue regeneration, increasing collagen deposition, and accelerating angiogenesis. Altogether, this innovative protein-polysaccharide bio-based composite hydrogel provides new insights and technical support for the development of more efficient wound treatment method, showing its potential application as a wound healing drug delivery vehicle.