The Blood Stops Here

RESEARCH HIGHLIGHTS

HYDROGELS catheters into the arterial vasculature and forelimb venous vasculature. Again, full occlusion of the target The blood stops here vessels was achieved, further demon- strating the translational potential of A shear-thinning hydrogel stops animal models, but tailored it so that this biomaterial. uncontrolled bleeding in blood it could be used with tools, imaging The fate of the biomaterial and vessels and conveys several technology and with the needs of the injured vessel after embolization advantages over existing emboli the end user (that is, the physician) are also important considerations. zation approaches, report Ali in mind.” Histological analysis of embolized Khademhosseini, Rahmi Oklu and Two salient features of their vessels revealed that remodelling colleagues in Science Translational hydrogel render it suitable for of the vessel occurs in concert Medicine. endovascular embolization: the with clearance of the biomaterial, Uncontrolled bleeding due to nanoplatelets can mimic platelet cells which is thought to be mediated by vascular injury is treated either with to induce blood clotting and the gel phagocytic cells. Consequently, there open surgery or, more recently, with exhibits shear-thinning behavior is a low risk of recanalization or frag- minimally invasive endovascular (that is, the viscosity decreases under mentation of the gel. Moreover, the embolization. The latter involves shear strain). This rheological behav- authors suggest that this process of guidance of metallic coils or liquid iour allows the gel to flow through remodelling and biomaterial clear- embolic agents with catheters and the catheter under mechanical ance provides the opportunity to wires to the site of bleeding, where pressure applied through a syringe. incorporate stimuli to, for example, clotting is induced to occlude the Once administered at the site of control angiogenesis. wounded blood vessel. However, this bleeding, the modulus recovers (that procedure comes with certain risks, is, the material solidifies) owing to We developed a including recanalization, coil migra- the reduced pressure, and a tight seal tion, coil compaction or toxicity, and is created. biomaterial not just for the adhesion between the liquid embolic After fine-tuning the viscoelastic bench or for use in animal agent and the catheter. and gelation properties to allow models, but tailored it so To overcome such problems, the delivery with standard catheters and that it could be used with researchers used a hydrogel, compris- needles, the researchers first tested ing gelatin and silicate nanoplatelets. their shear-thinning biomaterial tools, imaging technology The study was conceived upon in vitro. The gel was mechanically and with the needs of discussion between Khademhosseini stable under physiological pressures the end user (that is, the (an experimentalist) and Oklu (a and exhibited similar clotting to, and clinician–scientist). “My lab had higher hemocompatibility times than physician) in mind previously developed the biomaterial, metal coils. A particular advantage of but only after initiating interactions the gel is that — unlike metal coils — Given the success of this proof of with Rahmi and trying to solve the it does not require intrinsic throm- concept, the authors now intend to issues he has seen in his clinical bosis, which is beneficial for patients take their biomaterial into clinical practice, we realized its potential suffering from clotting disorders trials. “We have shown that the mat use for internal bleeding,” or who are taking anticoagulation erial works in pre-clinical models; in explains Khademhosseini. medication. particular, it seems to work in cases For Oklu, this research is The shear-thinning materials where existing therapies do not,” says a successful example of were then tested in vivo in both small Khademhosseini. “Now, we aim to patient-inspired bio (murine) and large (porcine) models. demonstrate the ultimate utility of engineering: “We devel- Upon direct injection into the fem- the material in the clinic.” oped a biomaterial oral artery, full occlusion occurred Adam Brotchie not just for the — revealed by computed tomography ORIGINAL ARTICLE Avery, R. K. et al. bench or for imaging — with the gel remaining An injectable shear-thinning biomaterial for use in at the site of injection. Having vali- endovascular embolization. Sci. Transl. Med. http:// dx.doi.org/10.1126/scitranslmed.aah5533 (2016) dated the effective embolization FURTHER READING Gaharwar, A. K. et al. Shear- L.Robinson/NPG of the shear-thinning biomaterial, thinning nanocomposite hydrogels for the the researchers then successfully treatment of hemorrhage. ACS Nano 8, 9833–9842 (2014) administered the material through