2. Academic Validation
  3. Hydrogel-immobilized coacervate droplets enable microenvironment-responsive sustained drug release to accelerate diabetic foot ulcers healing

Hydrogel-immobilized coacervate droplets enable microenvironment-responsive sustained drug release to accelerate diabetic foot ulcers healing

  • J Control Release. 2026 Jun 10:394:114858. doi: 10.1016/j.jconrel.2026.114858.
Hao Li 1,  Ruinan Wang 2,  Ziji Zhang 1,  Weitang Guo 2,  Zhiwen Li 1,  Xiayi Xu 3,  Weiming Liao 4,  Puyi Sheng 5,  Pengchao Zhao 6,  Liming Bian 7
Affiliations

Affiliations

  • 1 Department of Joint Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
  • 2 School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China.
  • 3 School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, China; Key Laboratory of Biomedical Materials of the Ministry of Education, South China University of Technology, Guangzhou 510006, China.
  • 4 Department of Joint Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. Electronic address: [email protected].
  • 5 Department of Joint Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. Electronic address: [email protected].
  • 6 School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, China; Key Laboratory of Biomedical Materials of the Ministry of Education, South China University of Technology, Guangzhou 510006, China. Electronic address: [email protected].
  • 7 School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, China; Key Laboratory of Biomedical Materials of the Ministry of Education, South China University of Technology, Guangzhou 510006, China. Electronic address: [email protected].
PMID: 41881075 DOI: 10.1016/j.jconrel.2026.114858
Abstract

Hydrogel-based wound dressings possess favorable intrinsic properties for the treatment of diabetic foot ulcers (DFUs); however, achieving sustained and environment-responsive drug release that can simultaneously address the multiple pathogenic factors of DFUs typically demands sophisticated molecular design and the incorporation of specific responsive motifs, thereby greatly increasing the overall complexity of hydrogel design. Herein, we present a delivery system by immobilizing electrostatically assembled coacervate droplets within a designed hydrogel matrix. The coacervate droplets create a molecularly crowded, high-density reservoir that can efficiently encapsulate diverse cargoes ranging from small molecules to macromolecules. Given the liquid nature of coacervates, their immobilization within a hydrogel matrix is essential to ensure structural stability. In the typical acidic microenvironment of DFUs, pH-triggered destabilization of the coacervates accelerates drug release. The single administration of this drug-laden hydrogel facilitates macrophage polarization toward the M2 phenotype in the inflammation phase, and enhance the survival, migration, and angiogenesis of endothelial cells in the proliferation phase, thereby accelerating the healing of DFUs. Considering the high loading capacity and compatibility of coacervates, this hydrogel-immobilized system can function as a versatile drug delivery platform to tackle diverse tissue-specific pathological conditions.

Keywords

Coacervate droplets; Diabetic foot ulcers; Drug delivery; Hydrogel.

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