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author:

Li, Zhendong (Li, Zhendong.) [1] | Chen, Longhui (Chen, Longhui.) [2] | Yang, Shasha (Yang, Shasha.) [3] | Han, Jinzhi (Han, Jinzhi.) [4] (Scholars:韩金志) | Zheng, Yunquan (Zheng, Yunquan.) [5] (Scholars:郑允权) | Chen, Zelong (Chen, Zelong.) [6] | Shi, Xianai (Shi, Xianai.) [7] (Scholars:石贤爱) | Yang, Jianmin (Yang, Jianmin.) [8] (Scholars:杨建民)

Indexed by:

EI Scopus SCIE

Abstract:

The healing process of diabetic foot ulcers is challenging due to the presence of a complex and severe inflammatory microenvironment, characterized by hyperglycemia, low pH, susceptibility to infection, vascular dysfunction, and over-expression of reactive oxygen species (ROS), which can potentially lead to amputation or even mortality. Herein, a glucose and pH dual-responsive hydrogel was designed and prepared by crosslinking phenylboronic acid-grafted quaternary chitosan (QF, 4 wt%) with dopamine-grafted oxidized hyaluronic acid (OD, 5 wt%) through phenylboronation, schiff-base reaction, and other techniques. The multifunctional QO/ @PV@AB7 hydrogel was prepared by incorporating pravastatin-loaded chitosan nanoparticles (CSNPs@PV, 2 mg/mL) and antimicrobial peptide AMP-AB7 loaded silica nanoparticles (SiO2NPs@AB7, 0.5 mg/mL). The results demonstrate that the QO/@PV@AB7 hydrogel exhibits good responsiveness to acidic conditions and high glucose levels, while effectively scavenging various types of ROS. Moreover, it exerted protective effects against oxidative stress on cells, enhanced HUVECs viability, and promoted angiogenesis. Notably, the QO/@PV@AB7 hydrogel displayed potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Additionally, in an MRSA-infected rat model of diabetic foot wounds, administration of the QO/ @PV@AB7 hydrogel led to increased secretion of pro-angiogenic factors such as vascular endothelial nitric oxide synthase (eNOS), vascular endothelial-generating factor (VEGF), and endothelial cell adhesion molecule (CD31). Furthermore, the hydrogel significantly reduced the levels of inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), while simultaneously increasing the levels of anti-inflammatory cytokines such as interleukin-10 (IL-10). The findings suggest that multifunctional hydrogels incorporating PV@CSNPs and SiO2NPs@AB7 demonstrate promising potential as a therapeutic approach for the treatment of diabetic foot. Statement of Significance: Here, a glucose and pH dual-responsive QO/@PV@AB7 hydrogel with antimicrobial and angiogenesis-promoting properties was developed for the treatment of infected wounds in diabetic feet. Our findings demonstrate that the proposed hydrogel exhibits good responsiveness, effectively scavenges various types of reactive oxygen species (DPPH, O2-,-OH, and ABTS+), provides protection against oxidative stress, enhances HUVECs cell viability, and promotes angiogenesis. Notably, it also demonstrates potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and E. coli. Additionally, in vivo experiments demonstrated that the hydrogel exhibited accelerated wound healing in MRSA-infected diabetic foot ulcers, with a reduction of four days compared to the control group.

Keyword:

Antimicrobial peptide Antioxidant Diabetic foot Pro-angiogenesis Responsive hydrogel

Community:

  • [ 1 ] [Li, Zhendong]Fuzhou Univ, Coll Biol Sci & Engn, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China
  • [ 2 ] [Chen, Longhui]Fuzhou Univ, Coll Biol Sci & Engn, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China
  • [ 3 ] [Yang, Shasha]Fuzhou Univ, Coll Biol Sci & Engn, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China
  • [ 4 ] [Han, Jinzhi]Fuzhou Univ, Coll Biol Sci & Engn, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China
  • [ 5 ] [Shi, Xianai]Fuzhou Univ, Coll Biol Sci & Engn, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China
  • [ 6 ] [Yang, Jianmin]Fuzhou Univ, Coll Biol Sci & Engn, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China
  • [ 7 ] [Zheng, Yunquan]Fuzhou Univ, Fujian Key Lab Med Instrument & Pharmaceut Technol, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China
  • [ 8 ] [Shi, Xianai]Fuzhou Univ, Fujian Key Lab Med Instrument & Pharmaceut Technol, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China
  • [ 9 ] [Yang, Jianmin]Fuzhou Univ, Fujian Key Lab Med Instrument & Pharmaceut Technol, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China
  • [ 10 ] [Chen, Zelong]900th Hosp Joint Logist Support Force, Dept Biomed Engn, 156 West Second Ring Rd, Fuzhou 350025, Peoples R China

Reprint 's Address:

  • 韩金志 杨建民

    [Han, Jinzhi]Fuzhou Univ, Coll Biol Sci & Engn, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China;;[Yang, Jianmin]Fuzhou Univ, Coll Biol Sci & Engn, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China;;[Chen, Zelong]900th Hosp Joint Logist Support Force, Dept Biomed Engn, 156 West Second Ring Rd, Fuzhou 350025, Peoples R China

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Source :

ACTA BIOMATERIALIA

ISSN: 1742-7061

Year: 2024

Volume: 190

Page: 205-218

9 . 4 0 0

JCR@2023

Cited Count:

WoS CC Cited Count: 8

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 2

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