@article{8e0f78aaf98544dc8cebf476dc6fae6c,
title = "Cyclodextrin Modulated Type I Collagen Self-Assembly to Engineer Biomimetic Cornea Implants",
abstract = "Collagen-rich tissues in the cornea exhibit unique and highly organized extracellular matrix ultrastructures, which contribute to its high load-bearing capacity and light transmittance. Corneal collagen fibrils are controlled during development by small leucine-rich proteoglycans (SLRPs) that regulate the fibril diameter and spacing in order to achieve the unique optical transparency. Cyclodextrins (CDs) of varying size and chemical functionality for their ability to regulate collagen assembly during vitrification process are screened in order to create biosynthetic materials that mimic the native cornea structure. Addition of βCD to collagen vitrigels produces materials with aligned fibers and lamellae similar to native cornea, resulting in mechanically robust and transparent materials. Biochemistry analysis revealed that CD interacts with hydrophobic amino acids in collagen to influence assembly and fibril organization. To translate the self-assembled collagen materials for cornea reconstruction, custom molds for gelation and vitrification are engineered to create βCD/Col implants with curvature matching that of the cornea. Acellular βCD/Col materials are implanted in a rabbit partial keratoplasty model with interrupted sutures. The implants demonstrate tissue integration and support re-epithelialization. Therefore, the addition of CD molecules regulates collagen self-assembly and provides a simple process to engineer corneal mimetic substitutes with advanced structural and functional properties.",
keywords = "collagen, cornea, cyclodextrins, fibril alignment, self-assembly",
author = "Shoumyo Majumdar and Xiaokun Wang and Sommerfeld, {Sven D.} and Chae, {Jemin Jeremy} and Athanasopoulou, {Evangelia Nefeli} and Shores, {Lucas S.} and Xiaodong Duan and Amzel, {L. Mario} and Francesco Stellacci and Oliver Schein and Qiongyu Guo and Anirudha Singh and Elisseeff, {Jennifer H.}",
note = "Funding Information: S.M. and X.W. contributed equally to this work. This research was supported by our sponsors Research to Prevent Blindness, National Eye Institute grant R01EY029055, Eyegenix LLC (Prime Sponsors US Department of Defense and US Army Medical Research and Material Command) and the Morton Goldberg Professorship. The authors thank our colleagues from Eyegenix LLC, Honolulu (Tony Lee, Derek Duan, Priscilla Carbajal, Jack England, and Kylie Matsumoto) for helpful discussions. We would also like to acknowledge Scot C. Kuo (Director), Michael Delannoy (Associate Director) and Barbara Smith (EM & Advanced Fluorescence Microscopy Specialist) at the Microscopy Facility at Johns Hopkins School of Medicine, and EY001765 Wilmer Core Grant for Vision Research, Microscopy and Imaging Core Module. The authors also thank Katherine Tripp (Center Manager) at the Center for Molecular Biophysics for her advice and training on the circular dichroism spectrometer. The authors acknowledge Archana Jaiswal (Principal Application Scientist) at Biolin Scientific for training and use of the QSense QCM-D machine. Further, the authors acknowledge Harry Saaverdra Espinoza, Postdoctoral Fellow in the Amzel Lab in Johns Hopkins School of Medicine for assistance with the ITC experiments. The authors also extend thanks to Caitlin Duckwall and Dhruv Majumdar for the digital illustrations. Publisher Copyright: {\textcopyright} 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2018",
month = oct,
day = "10",
doi = "10.1002/adfm.201804076",
language = "English (US)",
volume = "28",
journal = "Advanced Functional Materials",
issn = "1616-301X",
publisher = "Wiley-VCH Verlag",
number = "41",
}