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

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.