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Elastin-like Proteins to Support Peripheral Nerve Regeneration in Guidance Conduits
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    Elastin-like Proteins to Support Peripheral Nerve Regeneration in Guidance Conduits
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    • Riley A. Suhar
      Riley A. Suhar
      Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States
    • Laura M. Marquardt
      Laura M. Marquardt
      Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States
      Department of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305, United States
    • Shang Song
      Shang Song
      Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, United States
      More by Shang Song
    • Hana Buabbas
      Hana Buabbas
      Department of Biology, Stanford University, Stanford, California 94305, United States
      More by Hana Buabbas
    • Vanessa M. Doulames
      Vanessa M. Doulames
      Department of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305, United States
    • Patrik K. Johansson
      Patrik K. Johansson
      Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States
    • Katarina C. Klett
      Katarina C. Klett
      Program in Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, United States
    • Ruby E. Dewi
      Ruby E. Dewi
      Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States
      More by Ruby E. Dewi
    • Annika M. K. Enejder
      Annika M. K. Enejder
      Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States
    • Giles W. Plant
      Giles W. Plant
      Department of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305, United States
    • Paul M. George
      Paul M. George
      Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, United States
      Stanford Stroke Center, Stanford University School of Medicine, Stanford, California 94305, United States
    • Sarah C. Heilshorn*
      Sarah C. Heilshorn
      Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States
      *Email: [email protected] (S.C.H.).
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    ACS Biomaterials Science & Engineering

    Cite this: ACS Biomater. Sci. Eng. 2021, 7, 9, 4209–4220
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    https://doi.org/10.1021/acsbiomaterials.0c01053
    Published November 4, 2020
    Copyright © 2020 American Chemical Society

    Abstract

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    Synthetic nerve guidance conduits (NGCs) offer an alternative to harvested nerve grafts for treating peripheral nerve injury (PNI). NGCs have been made from both naturally derived and synthesized materials. While naturally derived materials typically have an increased capacity for bioactivity, synthesized materials have better material control, including tunability and reproducibility. Protein engineering is an alternative strategy that can bridge the benefits of these two classes of materials by designing cell-responsive materials that are also systematically tunable and consistent. Here, we tested a recombinantly derived elastin-like protein (ELP) hydrogel as an intraluminal filler in a rat sciatic nerve injury model. We demonstrated that ELPs enhance the probability of forming a tissue bridge between the proximal and distal nerve stumps compared to an empty silicone conduit across the length of a 10 mm nerve gap. These tissue bridges have evidence of myelinated axons, and electrophysiology demonstrated that regenerated axons innervated distal muscle groups. Animals implanted with an ELP-filled conduit had statistically higher functional control at 6 weeks than those that had received an empty silicone conduit, as evaluated by the sciatic functional index. Taken together, our data support the conclusion that ELPs support peripheral nerve regeneration in acute complete transection injuries when used as an intraluminal filler. These results support the further study of protein engineered recombinant ELP hydrogels as a reproducible, off-the-shelf alternative for regeneration of peripheral nerves.

    Copyright © 2020 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsbiomaterials.0c01053.

    • Figure S1: Elastin-Like Protein Amino Acid Analysis and Representative Spectra Figure S2: Elastin-Like Protein Crosslinking Schematic and Conduit Fabrication Photographs Figure S3: Representative Individual Electrophysiology Curves Table S1: Electrophysiology Data Summary Table S2: Sciatic Functional Index Data Summary Figure S4: Normalized Sciatic Functional Index Data Figure S5: Needle Poke Test: Methods, plots, and data summary Figure S6: Hot-Plate Test: Methods, Plots, and Data Summary Figure S7: Wet Muscle Mass: Methods, Plots, and Data Summary Figure S8: Coherent anti-Stokes Raman Spectroscopy of Elastin-Like Protein Hydrogel (PDF)

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    This article is cited by 17 publications.

    1. Riley A. Suhar, Michelle S. Huang, Renato S. Navarro, Giselle Aviles Rodriguez, Sarah C. Heilshorn. A Library of Elastin-like Proteins with Tunable Matrix Ligands for In Vitro 3D Neural Cell Culture. Biomacromolecules 2023, 24 (12) , 5926-5939. https://doi.org/10.1021/acs.biomac.3c00941
    2. Nuria Oliva, Mikyung Shin, Jason A. Burdick. Editorial: Special Issue on Advanced Biomedical Hydrogels. ACS Biomaterials Science & Engineering 2021, 7 (9) , 3993-3996. https://doi.org/10.1021/acsbiomaterials.1c01059
    3. Mako Kobayashi, Jun Negishi, Naoki Ishida, Yoshihide Hashimoto, Yoshihiro Sasaki, Kazunari Akiyoshi, Tsuyoshi Kimura, Akio Kishida. Effects of the matrix-bounded nanovesicles of high-hydrostatic pressure decellularized tissues on neural regeneration. Science and Technology of Advanced Materials 2024, 25 (1) https://doi.org/10.1080/14686996.2024.2404380
    4. Yuan Dai, Tingwei Lu, Linli Li, Fan Zhang, Haocheng Xu, Hailong Li, Weizhong Wang, Minghao Shao, Feizhou Lyu. Electrospun Composite PLLA‐PPSB Nanofiber Nerve Conduits for Peripheral Nerve Defects Repair and Regeneration. Advanced Healthcare Materials 2024, 13 (10) https://doi.org/10.1002/adhm.202303539
    5. Eugenio Redolfi Riva, Melis Özkan, Estefania Contreras, Sujeet Pawar, Ciro Zinno, Enrique Escarda-Castro, Jaehyeon Kim, Paul Wieringa, Francesco Stellacci, Silvestro Micera, Xavier Navarro. Beyond the limiting gap length: peripheral nerve regeneration through implantable nerve guidance conduits. Biomaterials Science 2024, 12 (6) , 1371-1404. https://doi.org/10.1039/D3BM01163A
    6. Francesca Santilli, Jessica Fabrizi, Costantino Santacroce, Daniela Caissutti, Zaira Spinello, Niccolò Candelise, Loreto Lancia, Fanny Pulcini, Simona Delle Monache, Vincenzo Mattei. Analogies and Differences Between Dental Stem Cells: Focus on Secretome in Combination with Scaffolds in Neurological Disorders. Stem Cell Reviews and Reports 2024, 20 (1) , 159-174. https://doi.org/10.1007/s12015-023-10652-9
    7. Jinguang Chen, Meiying Cui, Lianping He, Yeteng Mu, Nannan Hu, Xingang Guan. Engineered elastin-like polypeptide-based hydrogel delivering chemotherapeutics and PD-L1 antibodies for potentiated cancer immunotherapy. Journal of Materials Chemistry B 2023, 11 (43) , 10355-10361. https://doi.org/10.1039/D3TB01974H
    8. Linliang Wu, Hongxia Gao, Qi Han, Wenchao Guan, Shaolan Sun, Tiantian Zheng, Yaqiong Liu, Xiaolu Wang, Ran Huang, Guicai Li. Piezoelectric materials for neuroregeneration: a review. Biomaterials Science 2023, 11 (22) , 7296-7310. https://doi.org/10.1039/D3BM01111A
    9. Elena Stocco, Silvia Barbon, Diego Faccio, Lucia Petrelli, Damiana Incendi, Annj Zamuner, Enrico De Rose, Marta Confalonieri, Francesco Tolomei, Silvia Todros, Cesare Tiengo, Veronica Macchi, Monica Dettin, Raffaele De Caro, Andrea Porzionato. Development and preclinical evaluation of bioactive nerve conduits for peripheral nerve regeneration: A comparative study. Materials Today Bio 2023, 22 , 100761. https://doi.org/10.1016/j.mtbio.2023.100761
    10. Faranak Mankavi, Rana Ibrahim, Hongjun Wang. Advances in Biomimetic Nerve Guidance Conduits for Peripheral Nerve Regeneration. Nanomaterials 2023, 13 (18) , 2528. https://doi.org/10.3390/nano13182528
    11. Mahdis Shayan, Michelle S. Huang, Renato Navarro, Gladys Chiang, Caroline Hu, Beu P. Oropeza, Patrik K. Johansson, Riley A. Suhar, Abbygail A. Foster, Bauer L. LeSavage, Maedeh Zamani, Annika Enejder, Julien G. Roth, Sarah C. Heilshorn, Ngan F. Huang. Elastin‐like protein hydrogels with controllable stress relaxation rate and stiffness modulate endothelial cell function. Journal of Biomedical Materials Research Part A 2023, 111 (7) , 896-909. https://doi.org/10.1002/jbm.a.37520
    12. Elena Stocco, Silvia Barbon, Aron Emmi, Cesare Tiengo, Veronica Macchi, Raffaele De Caro, Andrea Porzionato. Bridging Gaps in Peripheral Nerves: From Current Strategies to Future Perspectives in Conduit Design. International Journal of Molecular Sciences 2023, 24 (11) , 9170. https://doi.org/10.3390/ijms24119170
    13. Hai‐qiang Zhang, Dong‐wei Lan, Xia Li, Zhi Li, Fang‐Yin Dai. Conductive and antibacterial scaffold with rapid crimping property for application prospect in repair of peripheral nerve injury. Journal of Applied Polymer Science 2023, 140 (5) https://doi.org/10.1002/app.53426
    14. Aiguo Jiang, Xinqiang Guan, Lianping He, Xingang Guan. Engineered elastin-like polypeptides: An efficient platform for enhanced cancer treatment. Frontiers in Pharmacology 2023, 13 https://doi.org/10.3389/fphar.2022.1113079
    15. Poornima Ramburrun, Pradeep Kumar, Elias Ndobe, Yahya E. Choonara. Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair. International Journal of Molecular Sciences 2021, 22 (21) , 11555. https://doi.org/10.3390/ijms222111555
    16. Wenhao Wang, Qian Deng, Tao Li, Yuehua Liu, Yang Liu, Yeye Sun, Changxu Deng, Xiaojun Zhou, Zhenjiang Ma, Lei Qiang, Jinwu Wang, Kerong Dai. Research Update on Bioreactors Used in Tissue Engineering. Journal of Shanghai Jiaotong University (Science) 2021, 26 (3) , 272-283. https://doi.org/10.1007/s12204-021-2293-5
    17. Daniel R. Hunt, Katarina C. Klett, Shamik Mascharak, Huiyuan Wang, Diana Gong, Junzhe Lou, Xingnan Li, Pamela C. Cai, Riley A. Suhar, Julia Y. Co, Bauer L. LeSavage, Abbygail A. Foster, Yuan Guan, Manuel R. Amieva, Gary Peltz, Yan Xia, Calvin J. Kuo, Sarah C. Heilshorn. Engineered Matrices Enable the Culture of Human Patient‐Derived Intestinal Organoids. Advanced Science 2021, 8 (10) https://doi.org/10.1002/advs.202004705

    ACS Biomaterials Science & Engineering

    Cite this: ACS Biomater. Sci. Eng. 2021, 7, 9, 4209–4220
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsbiomaterials.0c01053
    Published November 4, 2020
    Copyright © 2020 American Chemical Society

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