Controlling delivery properties of a waterborne, in-situ-forming biomaterial

Abstract

This study details efforts to transition an in-situ-gelling polymer for endovascular embolization from the bench-top to preclinical cerebral arteriovenous malformation animal model studies. The in-situ-forming gel is based on waterborne, reverse emulsion materials. For controlled embolization of vascular defects, it is crucial to understand the delivery properties of an in-situ-forming gel. Directing a liquid into a small cavity requires both precise control of the fluid flow, and depends upon minimal variability in the materials behavior. A 2(3) factorial experiment performed in the laboratory revealed that temperature, mixing time, and buffer strength are all significant factors affecting the gelation time of the specific system studied. All three factors were also seen to reduce the standard deviation on the gel times. Changing the temperature from 21.3 to 37.0 degrees C reduced the cross population variability from 6.0 +/- 3.3 min to 3.4 +/- 1.6 min. At 30-s premixing, the protocol produced an average gel time of 5.3 +/- 3.0 min, which was reduced to 3.3 +/- 1.2 min with 90 s. Finally, a 50 mM buffer solution provided a gel time of 6.5 +/- 3.2 min, which was reduced to 2.95 +/- 0.6 min at 100 mM. Viscosity data was analyzed to suggest a model for injection volume and viscosity.