Dual-sized hollow particle incorporated fibroin thermal insulating coatings on catheter for cerebral therapeutic hypothermia

Abstract

Selective endovascular hypothermia has been used to provide cooling-induced cerebral neuroprotection, but current catheters do not support thermally-insulated transfer of cold infusate, which results in an increased exit temperature, causes hemodilution, and limits its cooling efficiency. Herein, air-sprayed fibroin/silica-based coatings combined with chemical vapor deposited parylene-C capping film was prepared on catheter. This coating features in dual-sized-hollow-microparticle incorporated structures with low thermal conductivity. The infusate exit temperature is tunable by adjusting the coating thickness and infusion rate. No peeling or cracking was observed on the coatings under bending and rotational scenarios in the vascular models. Its efficiency was verified in a swine model, and the outlet temperature of coated catheter (75 μm thickness) was 1.8-2.0 °C lower than that of the uncoated one. This pioneering work on catheter thermal insulation coatings may facilitate the clinical translation of selective endovascular hypothermia for neuroprotection in patients with acute ischemic stroke.

Keywords: Catheter; Hypothermia; Silk fibroin; Stroke; Thermal insulation coating.

Graphical abstract

Fig. 1

Selective brain cooling and coating design. An illustration of selective brain cooling by the injection of cold infusate into the catheter from femoral artery to carotid artery (A). The warming effect on the cold infusate within the catheter induced by the heat transfer across catheter wall; and the presence of thermal insulation coatings increases thermal resistance of the catheter walls and results in lower exit temperature (B); schematics of air-spray coating process (C); and the design of three-layer coating model with interfacial layer (IL), thermal insulation layer (TL) and protective sealing layer (PL) (D).

Fig. 2

Thermal modelling of the heat transfer across the coatings. The schematic illustration of the coating model (a); temperature distribution (b) and contours of total heat flux (c) of a packing unit within the coatings (A). The illustration of the porous structure of the coatings by using mono-sized (a) and dual-sized hollow spheres (b), as well as the corresponding heat flux value (B). Numerical simulation of the temperatures (a) and the two-dimensional temperature distributions (b) along the catheter with different coating thickness at a infusion rate of 30 mL/min(C).

Fig. 3

Schematic diagram of the coating process, morphology characterization and thermal resistance evaluation. Optical photos of the pristine (upper panel) and coated catheters (lower panel); The three-layered structures of the coatings prepared by surface activation through dopamine polymerization (step 1), air spraying (step 2) and chemical vapor deposition of parylene-C (step 3) (A); SEM images of the prepared HSBP as well as the surface morphology of the substrate, TIC and TIC-P coatings (B); The exit temperature differences between the uncoated and coated catheters with different coating thickness through in vitro studies (C); and the illustration of the heat transfer process through different coatings (D).

Fig. 4

The in vitro evaluation of the cooling performance of thermal insulated catheter. Schematic illustration of the 1:1 simulated blood vessels and the insertion pathway (A); the picture of the temperature sensor at the catheter outlet (a); the perfusate temperature in perfusion as T₀ (b), aorta as T₁(c), catheter outlet as T₂ and MCA as T₃ (d). The comparison of the infusate temperatures by using coated and uncoated catheters at outlet (C), MCA (D), aorta (E) as well as their output cooling capacity (F) at infusion volume rate from 10 mL/min to 50 mL/min; the infusion volume required to target brain cooling temperature (G) and the related dilution rate of HCT (H) were presented. * represents p < 0.05 (compared with the uncoated group).

Fig. 5

In vitro biocompatible analysis of the samples. The immunofluorescence images of HUVEC, HSMC and RAW 264.7 cells after being cultured in the extraction media of the samples for 24 h (A) as well as their proliferation rate (B). The blood compatible evaluation of the samples was conducted by hemolysis rate and Fg absorption analysis (C). * represents p < 0.05 (compared with the NC group).

Fig. 6

Animal study results. The equipment setup of selectively endovascular hypothermia on swine model (a) and the timeline for each process (b) (A). The catheter was inserted into CCA (a) and nasopharyngeal temperature was detected by inserting the sensor into the pig nose as brain temperature (b) (B). The variation of saline outlet temperature (a) and tympanic temperature (b) along the cooling process were monitored (C). HE staining of CCA vessel (D). The summary and analysis of several selective brain cooling study results on swine, canine and monkey models, as well as two clinical trials; and the related references were listed in Table S2(E). The CCA is short for common carotid artery.