26/02/2026
Professor Shu Chang's team from Fuwai Hospital, China, in collaboration with Sun Yat-sen University, China, has achieved a world-first innovation with magnetically controlled injectable adhesive hydrogels, opening a new pathway for vascular interventional embolization therapy.
1.Research Background: Clinical Challenges in Vascular Repair
Vascular abnormalities, such as ruptured intracranial aneurysms, hemorrhage from arteriovenous malformations, and type II endoleaks following endovascular repair of abdominal aortic aneurysms, often lead to severe consequences. Current treatment modalities have significant limitations:
Metallic Coil Embolization: The occlusion rate is approximately 66%, making it difficult to achieve complete and stable aneurysm sealing.
Liquid Polymer Embolic Agents: The clinical success rate is about 68.4%, and they are prone to being washed away in the dynamic blood flow environment, making firm adhesion challenging.
Biological Environmental Challenges: Red blood cells, platelets, and plasma proteins in the blood can interfere with the contact between the hydrogel and the vessel wall, compromising the adhesion effect.
Consequently, the development of novel embolic materials that can be rapidly positioned, firmly adhere within dynamic blood flow, and possess excellent biocompatibility has become a critical clinical challenge that needs to be addressed.
2.Material Design: Synergistic Construction of Multifunctional iMAH
Component A
Main Ingredients: Quaternized chitosan, γ-Fe₂O₃@PDA nanoparticles, catechol-modified gelatin, metformin.
Function/Role: Magnetic responsiveness, tissue adhesion, stable dispersion.
Component B
Main Ingredients: Oxidized hyaluronic acid (with aldehyde groups)
Function/Role: Rapid cross-linking (via Schiff base formation)
Component C
Main Ingredients: Sodium periodate (NaIO₄)
Function/Role: Enhanced adhesion strength (via oxidative cross-linking)
Key Innovations:
Magnetic Responsiveness: The γ-Fe₂O₃@PDA nanoparticles exhibit excellent superparamagnetism (saturation magnetization of 49.2 emu/g), enabling targeted delivery guided by an external magnetic field.
Rapid Crosslinking: The material forms a gel approximately 2 seconds after mixing components A and B, effectively preventing it from being washed away by blood flow.
Enhanced Tissue Adhesion: Catechol groups chemically react with amino/thiol groups on the tissue surface. NaIO₄ further promotes oxidative crosslinking to form a dual-network structure, achieving an adhesion strength of up to 71 kPa.
Flowability Control: The introduction of Metformin (an FDA-approved drug) inhibits the physical solidification of gelatin at room temperature, ensuring smooth injectability.
3. Magnetically Controlled Delivery System: Precise Navigation with a Five-Axis Robot
To achieve precise intravascular delivery, the research team developed a five-axis magnetically controlled vascular robot system. Comprising four cylindrical permanent magnets and one central spherical magnet, this system generates a controllable magnetic field of 80–100 mT at the target site.
System Advantages:
Spatial Localization: By integrating optical localization with DSA imaging, it enables precise registration between the target site and the magnetic field.
Multi-DOF Control: Supports three translational (x, y, z) and two angular (α, β) movements, allowing flexible adjustment of the magnetic field direction.
Magnetic Force-Assisted Adhesion: The magnetic field presses the hydrogel against the vascular wall, extruding interfacial fluid to promote tissue contact and adhesion.
In Vitro Validation:
In simulated blood flow at 20 cm/s, iMAH can be magnetically guided into an aneurysm model.
Under dynamic blood pressure of 80–120 mmHg, iMAH achieves vascular embolization within approximately 5 minutes, with a leakage rate below 1/1000.
4.Functional Validation In Vitro and In Vivo
1. Wound Hemostasis and Vascular Embolization
Rat Liver Hemorrhage Model: Magnetically delivered iMAH achieved hemostasis within 14.6 ± 2.5 seconds, reducing blood loss by approximately 86%, significantly outperforming the non-magnetic control group.
Static Vascular Sealing Test: iMAH withstood a burst pressure of approximately 100 mmHg after embolizing blood vessels.
Dynamic Vascular Sealing Test: In a simulated Type II endoleak model, iMAH completely sealed branch arteries within 5 minutes under a blood flow pressure of 80 mmHg.
2. Blood Compatibility and Cytotoxicity
Hemolysis rate < 5%, meeting safety standards for biological materials.
Human umbilical vein endothelial cells cultured for 1–3 days showed no significant difference in proliferation rate compared to the control group, indicating no cytotoxicity.
3. Subcutaneous Implantation and In Vivo Degradation
Six weeks after subcutaneous implantation in rats, approximately 44.39% of the iMAH mass remained, demonstrating controlled degradation.
Serum markers for liver, heart, and kidney function showed no significant differences compared to the control group.
Histological examination of major organs revealed no abnormalities, suggesting good histocompatibility.
5.Large Animal Experiment: Embolization of Beagle Lumbar Arteries
To simulate a Type II endoleak following endovascular abdominal aortic aneurysm repair, the research team selected the third pair of lumbar arteries in a beagle dog model as the target vessels.
Experimental Procedure:
1. Preoperative Localization: Preoperative CT and intraoperative DSA were used to precisely locate the target vessels (approximately 1.8–2 mm in diameter, at a depth of about 52 mm).
2. Stent Deployment: A covered stent was partially deployed, preserving the ostia of the lumbar arteries.
3. Magnetic Field Application: The five-axis magnetically controlled robot applied an 80 mT magnetic field, precisely oriented toward the target lumbar artery.
4. iMAH Delivery: A 100 μL bolus of iMAH was delivered via a microcatheter, and the magnetic field was maintained for 10 minutes to ensure precise positioning and adhesion.
5. Postoperative Confirmation: Postoperative angiography confirmed complete occlusion of the target vessel, after which the instruments were withdrawn.
Results:
Immediate Outcome: Postoperative angiography showed complete occlusion of the target vessels, with no observable blood flow.
Follow-up (2 Months Post-Procedure): The beagle demonstrated a steady increase in body weight, and all blood biochemical parameters remained within normal ranges.
Histological Analysis: Histological examination of the heart, liver, spleen, lungs, and kidneys revealed no abnormalities.
6.Conclusion and Clinical Implications
This study has successfully designed and validated a magnetically controlled injectable adhesive hydrogel (iMAH) that integrates key advantages, including rapid crosslinking, magnetic-responsive navigation, strong tissue adhesion, and excellent biocompatibility. When combined with a five-axis magnetically controlled robotic system, this technology enables precise delivery and robust embolization within complex hemodynamic environments, offering a novel therapeutic strategy for the following clinical scenarios:
- Ruptured intracranial aneurysms;
- Embolization of arteriovenous malformations;
- Occlusion of Type II endoleaks following abdominal aortic aneurysm repair;
- Hemostasis for traumatic vascular rupture;
- Precision drug delivery in transarterial chemoembolization (TACE).
Future Perspectives:
- Further optimization of the magnetic control system's navigational capabilities within tortuous vessels.
- Validation of therapeutic efficacy in disease models such as aneurysms and aortic dissections.
- Advancement of material processing and delivery system standardization to facilitate clinical translation.
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