Balance of Macrophage Activation by a Complex Coacervate-Based Adhesive Drug Carrier Facilitates Diabetic Wound Healing

Ching Shuen Wang, Shen Dean Luo, Shihai Jia, Wilfred Wu, Shwu Fen Chang, Sheng Wei Feng, Chieh Hsiang Yang, Jiann Her Lin, Yinshen Wee

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Uncontrolled and sustained inflammation disrupts the wound-healing process and produces excessive reactive oxygen species, resulting in chronic or impaired wound closure. Natural antioxidants such as plant-based extracts and natural polysaccharides have a long history in wound care. However, they are hard to apply to wound beds due to high levels of exudate or anatomical sites to which securing a dressing is difficult. Therefore, we developed a complex coacervate-based drug carrier with underwater adhesive properties that circumvents these challenges by enabling wet adhesion and controlling inflammatory responses. This resulted in significantly accelerated wound healing through balancing the pro- and anti-inflammatory responses in macrophages. In brief, we designed a complex coacervate-based drug carrier (ADC) comprising oligochitosan and inositol hexaphosphate to entrap and release antioxidant proanthocyanins (PA) in a sustained way. The results from in vitro experiments demonstrated that ADC is able to reduce LPS-stimulated pro-inflammatory responses in macrophages. The ability of ADC to reduce LPS-stimulated pro-inflammatory responses in macrophages is even more promising when ADC is encapsulated with PA (ADC-PA). Our results indicate that ADC-PA is able to polarize macrophages into an M2 tissue-healing phenotype via up-regulation of anti-inflammatory and resolution of inflammatory responses. Treatment with ADC-PA around the wound beds fine-tunes the balance between the numbers of inducible nitric oxide synthase-positive (iNOS+) and mannose receptor-negative (CD206-) M1 and iNOS-CD206+ M2 macrophages in the wound microenvironment compared to controls. Achieving such a balance between the numbers of iNOS+CD206- M1 and iNOS-CD206+ M2 macrophages in the wound microenvironment has led to significantly improved wound closure in mouse models of diabetes, which exhibit severe impairments in wound healing. Together, our results demonstrate for the first time the use of a complex coacervate-based drug delivery system to promote timely resolution of the inflammatory responses for diabetic wound healing by fine-tuning the functions of macrophages.
原文英語
文章編號2351
期刊Antioxidants
11
發行號12
DOIs
出版狀態已發佈 - 12月 2022

ASJC Scopus subject areas

  • 食品科學
  • 生理學
  • 生物化學
  • 分子生物學
  • 臨床生物化學
  • 細胞生物學

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