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Effects of Polymer End-Group Chemistry and Order of Deposition on Controlled Protein Delivery from Layer-by-Layer Assembly

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† ‡ Departments of Orthopaedic Surgery, Bioengineering, and §Computer Science, Stanford University, Stanford, California 94305, United States
Cite this: Biomacromolecules 2013, 14, 3, 794–800
Publication Date (Web):January 29, 2013
Copyright © 2013 American Chemical Society

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    Abstract Image

    Layer-by-layer (LBL) assembly is an attractive platform for controlled release of biologics given its mild fabrication process and versatility in coating substrates of any shape. Proteins can be incorporated into LBL coatings by sequentially depositing oppositely charged polyelectrolytes, which self-assemble into nanoscale films on medical devices or tissue engineering scaffolds. However, previously reported LBL platforms often require the use of a few hundred layers to avoid burst release, which hinders their broad translation due to the lengthy fabrication process, cost, and batch-to-batch variability. Here we report a biodegradable LBL platform composed of only 10 layers with tunable protein release kinetics, which is an order of magnitude less than previously reported LBL platforms. We performed a combinatorial study to examine the effects of polymer chemistry and order of deposition of poly(β-amino) esters on protein release kinetics under 81 LBL assembly conditions. Using the optimal “polyelectrolyte couples” for constructing the LBL film, basic fibroblast growth factor (bFGF) was released gradually over 14 days with retained biological activity to stimulate cell proliferation. The method reported herein is applicable for coating various substrates including metals, polymers, and ceramics and may be used for a broad range of biomedical and tissue engineering applications.

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    Polymer characterization via NMR, along with data on the protein deposition as a function of time and protein concentration. This material is available free of charge via the Internet at

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    Cited By

    This article is cited by 16 publications.

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    2. Sajid Iqbal, Ying Qu, Zhonghua Dong, Jianxiong Zhao, Abdur Rauf Khan, Shams Rehman, Zhongxi Zhao. Poly (β‐amino esters) based potential drug delivery and targeting polymer; an overview and perspectives (review). European Polymer Journal 2020, 141 , 110097.
    3. Divakara S.S.M. Uppu, Michelle E. Turvey, Abdul Rahim Mohammed Sharif, Katell Bidet, Yanpu He, Victor Ho, Anagha D. Tambe, Julien Lescar, Ern Yu Tan, Katja Fink, Jianzhu Chen, Paula T. Hammond. Temporal release of a three-component protein subunit vaccine from polymer multilayers. Journal of Controlled Release 2020, 317 , 130-141.
    4. Yong Liu, Yuanfeng Li, Damla Keskin, Linqi Shi. Poly(β‐Amino Esters): Synthesis, Formulations, and Their Biomedical Applications. Advanced Healthcare Materials 2019, 8 (2)
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    6. Xilin Liu, Fei Han, Peng Zhao, Chao Lin, Xuejun Wen, Xiaojian Ye. Layer-by-layer self-assembled multilayers on PEEK implants improve osseointegration in an osteoporosis rabbit model. Nanomedicine: Nanotechnology, Biology and Medicine 2017, 13 (4) , 1423-1433.
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    8. Brian Amsden. Novel biodegradable polymers for local growth factor delivery. European Journal of Pharmaceutics and Biopharmaceutics 2015, 97 , 318-328.
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