Calcium Hydroxylapatite-Carboxymethylcellulose Gel Embolization in a Simulated Microvascular Environment: Occlusion, Retrograde Flow Dynamics, and Enzymatic Recanalization.

Abstract

The microvascular behavior of calcium hydroxylapatite-carboxymethylcellulose (CaHA-CMC) fillers during arterial embolization remains incompletely characterized, particularly with respect to distal occlusive potential, bolus size effects, retrograde dissemination dynamics, and recanalization strategies. To evaluate the dispersal of differentially dilute CaHA-CMC in a simulated microvascular environment, with emphasis on bolus volume effects on occlusive burden and retrograde flow, and the feasibility of enzymatic recanalization using systemic cellulase. A microvascular adaptation of the PULSAR system was used to simulate arterial flow through a branched network (1000-200 µm). CaHA-CMC gels were tested in undiluted and diluted forms (1:0.5, 1:1, 1:2) using 0.2 ml and 1 ml boluses delivered via 22G microcannula. Flow patterns, microchannel occlusion, and retrograde propagation were assessed via videography. Enzymatic recanalization was evaluated for systemic cellulase and hyaluronidase. Undiluted CaHA-CMC produced total microtubular occlusion, while diluted formulations demonstrated reduced occlusive frequency. All mixtures achieved some degree of distal propagation into ∼200-300 µm branches. A larger bolus volume significantly increased occlusive potential (57.1% vs 16.0%, p < 0.0001) and retrograde flow incidence (100% vs 10%, p = 0.005). Hyaluronidase produced a minimal effect on occlusion while cellulase achieved rapid and progressive recanalization within minutes, restoring near-complete system patency by 60 minutes. CaHA-CMC gels demonstrate significant distal microvascular occlusion potential highly influenced by dilution and bolus volume, with larger volumes increasing occlusive burden and retrograde dissemination. Cellulase-mediated degradation of CMC enables recanalization, suggesting a potential strategy for reversal of CaHA-CMC embolic occlusions.