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Updated: Jan 15, 2026
Injection of Hydrogel Biomaterial Scaffolds to The Brain After Stroke
Published on: October 1, 2020
An antagomiR-loaded β-peptide hydrogel promotes functional recovery in mice post-ischaemic stroke
Yi-Kai Chen1, Ketav Kulkarni2, Marie-Isabel Aguilar2
1Department of Pharmacology, Monash University, Clayton, VIC, 3800, Australia; Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
Abstract:
Ischaemic stroke is a leading cause of mortality and disability, arising from interrupted cerebral blood flow and subsequent neuronal death. MicroRNAs, particularly miR-181a, have emerged as promising therapeutic targets due to their roles in regulating apoptosis and oxidative stress. While miR-181a inhibition using antagomirs can improve neuronal survival, translation to clinical practice is hampered by inefficient delivery across the blood-brain barrier and poor pharmacokinetics. Here, we developed a series of novel β-peptide hydrogels as injectable delivery systems to encapsulate and release a miR-181a antagomir in a controlled manner within the infarct region. β-peptides were synthesised with varied incorporation of β-homolysine residues to modulate electrostatic interactions with nucleic acids. The resulting hydrogels demonstrated shear-thinning and self-healing properties, stiffness values within the physiological range of brain tissue and tunable nucleic acid release profiles extending over 3 weeks. Following photothrombotic stroke in mice, intracerebral injection of antagomir-loaded hydrogel achieved precise infarct delivery and sustained presence for at least 7 days. Although infarct size reduction was modest, functional recovery, measured by improved motor coordination in the hanging wire test, was significantly enhanced in the hydrogel-antagomir group compared with controls. These findings highlight β-peptide hydrogels as promising platforms for localised, sustained delivery of nucleic acid therapeutics. This work establishes proof-of-concept for hydrogel-mediated miRNA delivery in stroke and provides a foundation for further optimisation in clinically relevant models.
Insights
Novel beta-peptide hydrogels effectively delivered miR-181a antagomirs to stroke-affected brain regions in mice. This localized, sustained delivery improved functional recovery, showcasing potential for nucleic acid therapeutics in treating ischemic stroke.
Area of Science:
- Biomaterials Science
- Neuroscience
- Drug Delivery
Background:
- Ischemic stroke causes significant mortality and disability due to interrupted cerebral blood flow.
- MicroRNAs, like miR-181a, are implicated in neuronal apoptosis and oxidative stress post-stroke.
- Current miR-181a antagomir therapies face challenges with blood-brain barrier penetration and pharmacokinetics.
Purpose of the Study:
- To develop injectable beta-peptide hydrogels for localized, sustained delivery of miR-181a antagomirs.
- To evaluate the hydrogel's properties for brain tissue compatibility and therapeutic release.
- To assess the therapeutic efficacy of hydrogel-delivered antagomirs in a mouse model of ischemic stroke.
Main Methods:
- Synthesized beta-peptide hydrogels with varying beta-homolysine content for tunable nucleic acid binding.
- Characterized hydrogel properties including injectability, self-healing, stiffness, and drug release kinetics.
- Administered antagomir-loaded hydrogels via intracerebral injection in a photothrombotic stroke mouse model.
- Assessed infarct size and functional recovery using motor coordination tests.
Main Results:
- Developed beta-peptide hydrogels with physiological stiffness, shear-thinning, and self-healing properties.
- Achieved sustained release of miR-181a antagomirs from hydrogels over 3 weeks.
- Demonstrated precise infarct delivery and sustained presence of antagomirs in the brain for at least 7 days post-injection.
- Observed significant functional recovery in motor coordination, despite modest reduction in infarct size.
Conclusions:
- Beta-peptide hydrogels serve as effective platforms for localized, sustained delivery of nucleic acid therapeutics.
- Hydrogel-mediated delivery of miR-181a antagomirs shows promise for enhancing functional recovery after ischemic stroke.
- This study provides a proof-of-concept for hydrogel-based miRNA delivery in stroke, paving the way for further optimization.
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