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pH/Thermosensitive dual-responsive hydrogel based sequential delivery for site-specific acute limb ischemia
Teng Zhang1,2, Huan Ouyang3, Shichen Liu1,2
1Department of Vascular Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi, 330006, P. R. China. zwmsubmit@126.com.
Journal of Materials Chemistry. B
|September 7, 2022
Summary
This study introduces a smart hydrogel for acute limb ischemia (ALI). It releases melatonin to combat oxidative stress in the acute phase and diallyl trisulfide to promote healing in the chronic phase.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Vascular Surgery
Background:
- Acute limb ischemia (ALI) is a severe peripheral artery disease complication with distinct acute and chronic phases.
- Current treatments for ALI primarily focus on recanalization, with limited efficacy in managing oxidative stress and promoting angiogenesis.
- The microenvironment in ALI exhibits dynamic changes in pH and temperature, influencing disease progression.
Purpose of the Study:
- To develop an injectable, dual-responsive hydrogel system for targeted therapy in both acute and chronic phases of ALI.
- To address the limitations of current ALI treatments by scavenging reactive oxygen species (ROS) and promoting angiogenesis.
Main Methods:
- Fabrication of a pH and temperature dual-responsive hydrogel (FHSgel) from poloxamer 407, hydroxymethyl cellulose, and sodium alginate.
- Encapsulation of melatonin and diallyl trisulfide-loaded biodegradable hollow mesoporous silica nanoparticles (DATS@dHMSNs) within the FHSgel.
- Evaluation of the hydrogel's intelligent release capabilities in response to ALI-specific microenvironmental changes (pH and temperature).
Main Results:
- The FHSgel demonstrated pH-triggered release of melatonin in the acute phase to scavenge ROS.
- The hydrogel exhibited temperature-triggered sustained release of DATS@dHMSNs in the chronic phase, generating hydrogen sulfide (H2S).
- Melatonin effectively scavenged ischemia-induced ROS, while H2S promoted angiogenesis and microcirculation reconstruction.
Conclusions:
- The developed FHSgel acts as an intelligent therapeutic system for ALI, effectively managing both acute and chronic phases.
- This dual-responsive hydrogel offers a promising strategy to overcome the limitations of current ALI treatments.
- The combination of melatonin and DATS@dHMSNs holds potential for enhancing recovery and improving outcomes in patients with ALI.
