Original Article
Inflammatory response to implantation of transparent nanocrystalline yttria-stabilized zirconia using a dorsal window chamber model

https://doi.org/10.1016/j.nano.2016.04.009Get rights and content

Abstract

The long-range goal of the windows to the brain (WttB) is to improve patient care by providing a technique for delivery and/or collection of light into/from the brain, on demand, over large areas, and on a chronically-recurring basis without the need for repeated craniotomies. To evaluate the potential of nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant for optical therapy and imaging, in vivo biocompatibility was studied using the dorsal window chamber model in comparison with control (no implant) and commercially available cranial implant materials (PEEK and PEKK). The host tissue response to implant was characterized by using transillumination and fluorescent microscopy to measure leukocyte adhesion, blood vessel diameter, blood flow rate, and vascular permeability over two weeks. The results indicated the lack of inflammatory reaction of the host tissue to nc-YSZ at the microscopic level, suggesting that nc-YSZ is a good alternative material for cranial implants.

Graphical Abstract

We evaluated in vivo biocompatibility of nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant using dorsal window chamber model (DWCM) in comparison with control (no implant) and commercially available cranial implant materials (PEEK and PEKK). DWCM contains striated muscle and skin, allowing for repeated analysis of the microcirculation in the awake hamster. Here a nc-YSZ sample (*) was implanted. (B, C, D) Representative intravital fluorescence microscopy image of the microcirculation under the nc-YSZ implant 15 days after implantation with: (B) white light; (C) green-light epi-illumination upon injection of Rhodamine 6G for labeling leukocytes. (D) Blue-light epi-illumination upon injection of macromolecular fluorescent dye FITC Dextran.

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Section snippets

Animal model and implantation

Animal handling and care were provided following the Care and Use of Laboratory Animals.23 All animal experiments were conducted under a protocol approved by the University of California, San Diego Institutional Animal Care and Use Committee (S04052, Microhemodynamics of Hamster Skinfold Model, approved on 04/04/2015). Male golden Syrian hamsters of 50-70 g were fitted with a one-sided window chamber consisting of two titanium supports, one of which holds a 12-mm-diameter glass window. The

Results

All animals completed the study protocol without visible sign of discomfort. Animals were observed resting and periodically eating throughout the experiment. In Figure 2, Figure 3, Figure 4, week 1 consisted of data collected on days 5 and 7, and week 2 consisted of data collected on days 10, 12, and 15.

Discussion

In this report, the DWCM was used to study the microcirculation by means of intravital microscopy using transillumination. Previously, this model proved to be ideal for the systematic in vivo analysis of the host tissue interaction with biomaterials.18, 19, 32 Specifically, this model has been used to study the host tissue response to cranioplasty biomaterials such as ceramic calcium phosphate compounds20, 21 and titanium.22, 32, 33

Conventionally-processed microcrystalline YSZ (mc-YSZ) has

Acknowledgments

The authors would like to acknowledge the American Society for Lasers in Medicine and Surgery (ASLMS) Student Research Grant awarded to Y. D. to conduct this study and for the travel grant awarded to Y. D. to present research leading to this study at the 34th Annual ASLMS Conference, Phoenix, AZ in April 2014. Y. D. also thanks the support of the UCMEXUS Dissertation Research Grant and Y. D. and G. A. thank the support of the UC MEXUS-CONACYT Collaborative Research Grant. The authors would also

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