Wang Ben,Shen Jie,Huang Chenyang,Ye Zhicheng,He Jiajun,Wu Xinyu,Guo Zhiguang,Zhang Li,Xu Tiantian
Small materials with pliability and untethered mobility are particularly suitable for minimally invasive medical interventions inside the body. However, the capabilities and applicability of such soft ‘robots’ are restricted by foreign-body responses to them and by the need to get them cleared from the body after the intervention. Here we report the development of biodegradable magnetized biohybrid blood hydrogel fibres that evade immune recognition, and their applicability for targeted intracranial tumour therapy with real-time tracking through X-ray fluoroscopy. The gel fibres can be made of the patient’s own blood mixed with a small amount of magnetic particles and can be produced in about 15 min. We show that the locomotion of intracranially injected gel fibres through cerebrospinal fluid can be remotely controlled under a magnetic field and fluoroscopically tracked, and that a drug encapsulated in the gels can be released on demand under magnetic control, as we show for the delivery of doxorubicin to intracranial tumours in the minipigs. Biodegradable soft actuatable materials that avoid foreign-body responses may aid the development of personalized targeted interventions.
It is very challenging to visualize implantable medical devices made of biodegradable polymers in deep tissues. Herein, we designed a novel macromolecular contrast agent with ultrahigh radiopacity (iodinate content > 50%) via polymerizing an iodinated trimethylene carbonate monomer into the two ends of poly(ethylene glycol) (PEG). A set of thermosensitive and biodegradable polyester-PEG-polyester triblock copolymers with varied polyester compositions synthesized by us, which were soluble in water at room temperature and could spontaneously form hydrogels at body temperature, were selected as the demonstration materials. The addition of macromolecular contrast agent did not obviously compromise the injectability and thermogelation properties of polymeric hydrogels, but conferred them with excellent X-ray opacity, enabling visualization of the hydrogels at clinically relevant depths through X-ray fluoroscopy or Micro-CT. In a mouse model, the 3D morphology of the radiopaque hydrogels after injection into different target sites was visible using Micro-CT imaging, and their injection volume could be accurately obtained. Furthermore, the subcutaneous degradation process of a radiopaque hydrogel could be non-invasively monitored in a real-time and quantitative manner. In particular, the corrected degradation curve based on Micro-CT imaging well matched with the degradation profile of virgin polymer hydrogel determined by the gravimetric method. These findings indicate that the macromolecular contrast agent has good universality for the construction of various radiopaque polymer hydrogels, and can nondestructively trace and quantify their degradation in vivo . Meanwhile, the present methodology developed by us affords a platform technology for deep tissue imaging of polymeric materials.
危险品化学品经营许可证（带存储）