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Research Papers

Particulate Release From Nanoparticle-Loaded Shape Memory Polymer Foams

[+] Author and Article Information
Adam L. Nathan, Grace K. Fletcher, Mary Beth B. Monroe, Scott M. Herting, Brandis K. Keller

Biomedical Engineering,
Texas A&M University,
College Station, TX 77843

Wonjun Hwang

Shape Memory Medical, Inc.,
Santa Clara, CA 95054

Sayyeda M. Hasan

Biomedical Engineering,
Texas A&M University,
College Station, TX 77843;
Shape Memory Medical, Inc.,
Santa Clara, CA 95054

Duncan J. Maitland

Biomedical Engineering,
Texas A&M University,
College Station, TX 77843;
Shape Memory Medical, Inc.,
Santa Clara, CA 95054
e-mail: djmaitland@tamu.edu

Manuscript received May 26, 2016; final manuscript received December 7, 2016; published online January 16, 2017. Assoc. Editor: Rafael V. Davalos.

J. Med. Devices 11(1), 011009 (Jan 16, 2017) (9 pages) Paper No: MED-16-1233; doi: 10.1115/1.4035547 History: Received May 26, 2016; Revised December 07, 2016

Highly porous, open-celled shape memory polymer (SMP) foams are being developed for a number of vascular occlusion devices. Applications include abdominal aortic and neurovascular aneurysm or peripheral vascular occlusion. A major concern with implanting these high surface area materials in the vasculature is the potential to generate unacceptable particulate burden, in terms of number, size, and composition. This study demonstrates that particulate numbers and sizes in SMP foams are in compliance with limits stated by the most relevant standard and guidance documents. Particulates were quantified in SMP foams as made, postreticulation, and after incorporating nanoparticles intended to increase material toughness and improve radiopacity. When concentrated particulate treatments were administered to fibroblasts, they exhibited high cell viability (100%). These results demonstrate that the SMP foams do not induce an unacceptable level of risk to potential vascular occlusion devices due to particulate generation.

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References

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Figures

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Fig. 3

Schematic representation of the cyclic wash protocol used to evaluate foam samples for particulate generation

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Fig. 2

Mechanical reticulation process. (a) Scanning electron microscopy (SEM) image of SMP foam prior to reticulation, (b) SMP foam block is repetitively raised and lowered on a vibrating platform allowing the floating nitinol pin array to mechanically reticulate the foam, and (c) SEM image of SMP foam postreticulation.

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Fig. 7

Numbers of particulates (a) ≥10 μm and (b) ≥25 μm from foams with W, SiO2, and Al2O3 filler types. n = 5; Mean ± standard deviation displayed; *p < 0.05 relative to control; **p < 0.05 between bracketed groups. USP 788 limit for particulates ≥10 μm = 6000; limit ≥25 μm = 600.

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Fig. 4

Particulates ≥50 μm generated over three inversion cycles for all foam chemistries tested. n = 5; Mean ± standard deviation displayed. No USP or FDA limit for particulates ≥50 μm.

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Fig. 6

Numbers of particulates (a) ≥10 μm and (b) ≥25 μm from 1 wt.% Al2O3 foams with varying monomer ratios of 50:50 HDI:TMHDI, 20:80 HDI:TMHDI, and 100% TMHDI. n = 5; Mean ± standard deviation displayed; *p < 0.05 relative to control; **p < 0.05 between the bracketed groups. USP 788 limit for particulates ≥10 μm = 6000; limit ≥25 μm = 600.

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Fig. 5

Number of particulates (a) ≥10 μm and (b) ≥25 μm from control foams that were reticulated and nonreticulated over three inversion cycles. n = 5; Mean ± standard error displayed; *p < 0.05 relative to control. USP limit for particulates ≥10 μm = 6000; limit ≥25 μm = 600.

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Fig. 8

Numbers of particulates (a) ≥10 μm and (b) ≥25 μm from foams with varying weight percentages of W. n = 5; Mean ± standard deviation displayed; *p < 0.05 relative to control; **p < 0.05 between bracketed groups. USP limit for particulates ≥10 μm = 6000; limit ≥25 μm = 600.

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Fig. 10

Cell viability of 3T3 fibroblasts determined by neutral red uptake assay. n = 5; Mean ± standard error displayed. No significant differences were observed between the treatment groups.

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Fig. 9

Numbers of particulates (a) ≥10 μm and (b) ≥25 μm from foams with varying volume percentages of W. n = 5; Mean ± standard deviation displayed; *p < 0.05 relative to control; **p < 0.05 between bracketed groups. USP 788 limit for particulates ≥10 μm = 6000; limit ≥25 μm = 600.

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Fig. 1

Three-step foaming process. (a) Prepolymer solution is synthesized and cured for 36 h. (b) The resulting prepolymer is mixed with surfactants and nanoparticle fillers to make the side A mixture. The hydroxyl components, water, and catalysts are added to the side B mixture. (c) Side A and side B are mixed and a blowing agent is added to initiate the foam blowing process. Foams cured in the oven at 90 °C for 20 min.

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