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A biomimetic supramolecular hydrogel enabling sequential dual-agent release reprograms the inflammatory
Ziming Zhu1, Huilin Huo1, Xiaofei Liu1
1Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China.
Acta Biomaterialia
|July 16, 2026
Summary
This study presents a novel hydrogel for peripheral nerve repair, enhancing regeneration by controlling inflammation and delivering key growth factors sequentially. The engineered hydrogel successfully restored nerve function in rats.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Neuroscience
Background:
- Peripheral nerve injury (PNI) repair is limited by inflammation and lack of bioactive factors.
- Conventional hydrogels lack dynamic responsiveness, neural biomimicry, and inflammation regulation.
- Existing treatments struggle to create an optimal microenvironment for nerve regeneration.
Purpose of the Study:
- To engineer a biomimetic supramolecular hydrogel for reprogramming the immune microenvironment and promoting PNI repair.
- To achieve sequential release of therapeutic agents for sustained nerve regeneration.
- To develop a minimally invasive and adaptable treatment for peripheral nerve defects.
Main Methods:
- Fabrication of a supramolecular hydrogel (QK@CM-CTS/OCS-DA) via carboxymethyl chitosan (CM-CTS) and oxidized chondroitin sulfate (OCS) self-assembly.
- Incorporation and sequential release of a VEGF mimetic peptide (QK) and dopamine (DA).
- In vivo assessment of hydrogel biocompatibility, degradation, immunomodulation, and therapeutic efficacy in a rat sciatic nerve injury model.
Main Results:
- The QK@CM-CTS/OCS-DA hydrogel demonstrated injectability, self-healing, structural stability, and cytocompatibility.
- In vivo implantation showed no significant inflammation and near-complete degradation within 6 weeks.
- The hydrogel successfully promoted M2 macrophage polarization, angiogenesis, Schwann cell migration, axonal extension, myelination, and restored nerve function and motor recovery in rats.
Conclusions:
- The developed QK@CM-CTS/OCS-DA hydrogel effectively reprograms the inflammatory microenvironment and provides sequential delivery of bioactive factors.
- This biomimetic hydrogel offers a promising therapeutic strategy for peripheral nerve regeneration by creating a conducive environment for nerve repair.
- The study highlights the potential of combining dynamic material design with biological effects for advanced PNI treatment.
