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Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
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Rate-programmed drug delivery systems (DDS) are designed to release drugs at specific, controlled rates to maintain consistent therapeutic levels. These systems are categorized based on their release mechanisms, including dissolution-controlled DDS, diffusion-controlled DDS, and combined dissolution-diffusion-controlled DDS.In dissolution-controlled DDS, the release rate depends on the slow dissolution of the drug itself or the surrounding matrix. Drugs with inherently slow dissolution rates,...
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Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release
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ROS-Triggered Microgels for Programmable Drug Release in Volumetric Muscle Loss Repair.

Seungjun Lee1, Goeun Choe1, Junghyun Kim1

  • 1School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, Republic of Korea.

Advanced Healthcare Materials
|October 6, 2025
PubMed
Summary

Reduced graphene-containing hyaluronic acid microgels (rGHMs) offer a promising therapy for volumetric muscle loss (VML). These microgels deliver curcumin in response to reactive oxygen species (ROS), enhancing muscle regeneration and strength recovery.

Keywords:
curcumingraphene oxidehyaluronic acidmicrogelvolumetric muscle loss

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Tissue Engineering

Background:

  • Volumetric muscle loss (VML) leads to significant muscle depletion and fibrosis, hindering effective regeneration.
  • Current treatments for VML face challenges in promoting substantial muscle repair and functional recovery.
  • Reactive oxygen species (ROS) play a dual role in VML, contributing to damage but also signaling for repair.

Purpose of the Study:

  • To develop multifunctional reduced graphene-containing hyaluronic acid microgels (rGHMs) for VML treatment.
  • To create a platform for ROS-scavenging and ROS-responsive curcumin delivery.
  • To evaluate the efficacy of rGHMs in promoting skeletal muscle regeneration in a VML mouse model.

Main Methods:

  • rGHMs were synthesized using water-in-oil emulsion and chemical reduction.
  • Curcumin-loaded rGHMs (Cur/rGHMs) were characterized for antioxidant capacity, drug loading, and ROS-triggered release.
  • In vitro cytocompatibility and ROS protection assays were performed using C2C12 myoblasts.
  • In vivo studies involved implanting Cur/rGHMs into a mouse VML model to assess muscle regeneration, strength, fibrosis, vascularization, and inflammation.

Main Results:

  • rGHMs exhibited superior ROS-scavenging and controlled curcumin release in response to ROS (2.6-fold increase with H2O2).
  • In vitro studies showed rGHMs were cytocompatible and protected myoblasts from ROS-induced damage.
  • In vivo, Cur/rGHMs significantly improved muscle regeneration, achieving 89.0% strength recovery, 51.0% fibrosis reduction, and a 2.3-fold increase in vascularization.
  • Treatment attenuated inflammatory macrophage infiltration and increased centronucleated muscle fibers.

Conclusions:

  • rGHMs serve as effective ROS-responsive drug delivery vehicles for VML treatment.
  • Programmed curcumin delivery by rGHMs promotes significant skeletal muscle regeneration and functional recovery.
  • This ROS-responsive microgel platform presents a promising therapeutic strategy for VML.