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Reactive Oxygen Species Scavenging Functional Hydrogel Delivers Procyanidins for the Treatment of Traumatic Brain
Xuyang Huang1,2, Yongqing Ye1,2, Jianyong Zhang1
1Department of Neurosurgery, The Suqian Clinical College of Xuzhou Medical University, Jiangsu University, Suqian 223800, People's Republic of China.
Abstract:
Traumatic brain injury (TBI) is accompanied by the overload of reactive oxygen species (ROS), which can result in secondary brain injury. Although procyanidins (PCs) have a powerful free radical scavenging capability and have been widely studied in the treatment of TBI, conventional systemic drug therapy cannot make the drug reach the targeted area in the early stage of TBI and will cause systemic side effects because of the presence of the blood-brain barrier (BBB). To address this tissue, we designed and fabricated a ROS-scavenging functional hydrogel loaded PC (GelMA-PPS/PC) to deliver the drug by responding to the traumatic microenvironment. In situ injection of the GelMA-PPS/PC hydrogel effectively avoided the BBB and was directly applied to the surface of brain tissue to target the traumatic area. Hydrophobic poly(propylene sulfide)60 (PPS60), an ROS quencher and H2O2-responsive substance, was covalently bound to GelMA and exposed in response to the trauma microenvironment. At the same time, the H2O2 response of PPS60 further caused the structure of the hydrogel to degrade and release the encapsulated PC. Then PC could regulate the oxidative stress response in the cells and synergistically deplete ROS to play a neurotrophic protective role. This work suggests a novel method for the treatment of secondary brain injury by inhibiting the oxidative stress response after TBI.
Insights
A novel hydrogel loaded with procyanidins (PCs) effectively delivers treatment directly to traumatic brain injury (TBI) sites, bypassing the blood-brain barrier to reduce oxidative stress and protect brain tissue.
Area of Science:
- Biomaterials Science
- Neuroscience
- Regenerative Medicine
Background:
- Traumatic brain injury (TBI) leads to excessive reactive oxygen species (ROS), causing secondary brain damage.
- Conventional systemic drug delivery faces challenges due to the blood-brain barrier (BBB), limiting early TBI treatment efficacy and causing side effects.
Purpose of the Study:
- To develop a ROS-scavenging hydrogel for targeted drug delivery to TBI sites.
- To overcome BBB limitations and systemic side effects in TBI treatment.
Main Methods:
- Fabrication of a functional hydrogel (GelMA-PPS/PC) loaded with procyanidins (PCs).
- Incorporation of ROS-quenching poly(propylene sulfide)60 (PPS60) responsive to the trauma microenvironment.
- In situ injection of the hydrogel directly onto brain tissue to target the traumatic area.
Main Results:
- The GelMA-PPS/PC hydrogel successfully delivered PCs to the TBI site, bypassing the BBB.
- The hydrogel degraded in response to H2O2, releasing PCs and scavenging ROS.
- PCs regulated cellular oxidative stress, depleted ROS, and provided neurotrophic protection.
Conclusions:
- The developed hydrogel offers a novel, targeted approach for treating secondary brain injury post-TBI.
- This method effectively inhibits oxidative stress and protects neural tissue by leveraging a responsive drug delivery system.
