Tailoring self-assembled granular hydrogels (GHs) for immunomodulation and chronic wound healing
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PUBLIC SUMMARY
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Integrating click chemistry and phase separation is feasible for preparing granular hydrogels (GHs).
GHs with rationally selected bioactive compounds can accelerate the healing of chronic and infected wounds.
GHs with tailored biofunctions are promising for applications in immunomodulation and tissue regeneration.
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ABSTRACT
Granular hydrogels (GHs) hold a prominent position in tissue engineering and drug delivery due to their unique physicochemical properties. However, challenges still exist in tailoring bioactive GHs. This study presents a straightforward approach for preparing GHs with on-demand bioactivity. By utilizing the click chemistry of nucleophilic opening of epoxides by amines, in conjunction with the in-situ formation of poly(amino alcohol ethers) (MDP) prepolymers and lignosulfonate (LS) complexation-mediated phase separation, we have developed a new family of poly(amino alcohol ethers)-based GHs, named MDPS. MDPS exhibits microstructures with interconnected microgels, which have excellent hemocompatibility, cytocompatibility, and antioxidative properties. Moreover, by incorporating bioactive compounds within the microgel units, the curcumin-loaded MDPS exhibits outstanding anti-inflammatory effects in macrophage polarization, subsequently accelerating wound healing in a diabetic wound model. We further validate the feasibility of our approach to tailoring GHs with on-demand bioactivity by substituting LS with tannic acid (TA) to generate another type of GH, named MDPT, which exhibits excellent antibacterial properties both in vitro and in an S. aureus-infected wound model. Finally, the universal applicability of the proposed strategy is further demonstrated by utilizing two additional alternatives, sodium phytate (SP) and fucoidan (FCD), to prepare functional GHs. Overall, we develop a rapid and environmentally friendly strategy for tailoring functional GHs and demonstrate their versatile functions and bioactivities in two wound models. The approach presented here enables the customized design of bioactive GHs to advance applications in tissue regeneration and drug delivery. -
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REFERENCES
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Wan Y., Li S., Han J., et al. (2025). Tailoring self-assembled granular hydrogels (GHs) for immunomodulation and chronic wound healing. The Innovation Materials 3:100154. https://doi.org/10.59717/j.xinn-mater.2025.100154
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Wan Y., Li S., Han J., et al. (2025). Tailoring self-assembled granular hydrogels (GHs) for immunomodulation and chronic wound healing. The Innovation Materials 3:100154. https://doi.org/10.59717/j.xinn-mater.2025.100154
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Figure 1.
Tolerated self-assembled granular hydrogels (GHs) as immunoregulatory niches for diabetic or bacteria-infected wound repair
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Figure 2.
Characterizations of the MDPS GHs prepared with different concentrations of lignin sulfonate (LS) solution
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Figure 3.
In vitro cell studies
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Figure 4.
Effects of the MDPS8-Cur hydrogel in promoting diabetic wound healing
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Figure 5.
Stained sections of wound tissues on day 7 and quantitative analysis
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Figure 6.
Characterizations of the MDPS granular hydrogels prepared with different concentrations of TA solution
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Figure 7.
Effects of the MDPT8 hydrogel on promoting wound healing in S. aureus-infected wounds
