Tobacco Mosaic Virus Functionalized Alginate Hydrogel Scaffolds for Bone Regeneration in Rats with Cranial DefectClick to copy article linkArticle link copied!
- Jittima Amie Luckanagul
- Kamolrat Metavarayuth
- Sheng Feng
- Phudit Maneesaay
- Amy Y. Clark
- Xiaoming Yang
- Andrés J. García
- Qian Wang
Abstract

Plant viruses have been highlighted among material research due to their well-defined structures in nanoscale, monodispersity, stability, and chemical functionalities. Each of the thousands coat protein subunits on a viral nanoparticle can be homogeneously modified, chemically and genetically, with a functional ligand leading to a high-density and spatial distribution of ligands on each particle (multivalency). Previous reports from our group have evidenced that substrates coated with Tobacco mosaic virus (TMV) and its mutant promote early osteogenesis of mesenchymal stem cells (MSCs). We then fabricated a three-dimensional (3D) biopolymeric scaffold with rod-like TMV in the form of a sponge-like hydrogel for tissue engineering purposes. The hydrogel was functionalized with the cellular recognition peptide, arginine–glycine–aspartic acid (RGD), through an incorporation of an RGD mutant of TMV (TMV-RGD). The virus-functionalized hydrogel materials were shown to aid bone differentiation of MSCs in vitro. Herein, we performed an in vivo study based on the TMV and TMV-RGD hydrogels in Sprague–Dawley rats with cranial bone defects. This report substantiated the hypothesis that TMV-functionalized hydrogel scaffolds did not cause systemic toxicity when implanted in the defect site and that the TMV-based hydrogel platform can support cell localization and can be further optimized for bone regeneration and repair.
Cited By
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by ACS Publications if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
This article is cited by 38 publications.
- Xianxun Sun, Tao Tian, Yindong Lian, Zongqiang Cui. Current Advances in Viral Nanoparticles for Biomedicine. ACS Nano 2024, 18
(50)
, 33827-33863. https://doi.org/10.1021/acsnano.4c13146
- Wei Zhou, Qianming Li, Ruixiang Ma, Wei Huang, Xianzuo Zhang, Yingsheng Liu, Ze Xu, Linlin Zhang, Meng Li, Chen Zhu. Modified Alginate-Based Hydrogel as a Carrier of the CB2 Agonist JWH133 for Bone Engineering. ACS Omega 2021, 6
(10)
, 6861-6870. https://doi.org/10.1021/acsomega.0c06057
- Xueli Zhi, Chunxiong Zheng, Jie Xiong, Jianyao Li, Chenxi Zhao, Linqi Shi, Zhenkun Zhang. Nanofilamentous Virus-Based Dynamic Hydrogels with Tunable Internal Structures, Injectability, Self-Healing, and Sugar Responsiveness at Physiological pH. Langmuir 2018, 34
(43)
, 12914-12923. https://doi.org/10.1021/acs.langmuir.8b02526
- Guangzhao Zhang, Yunhua Chen, Yonghong Deng, and Chaoyang Wang . A Triblock Copolymer Design Leads to Robust Hybrid Hydrogels for High-Performance Flexible Supercapacitors. ACS Applied Materials & Interfaces 2017, 9
(41)
, 36301-36310. https://doi.org/10.1021/acsami.7b11572
- Akram Nadi, Elahe Soltani Fard, Fatemeh Karimzadeh, Fatemeh Elahian, Seyed Abbas Mirzaei. Genetic Engineering Revolutionized Scaffold‐Based Bone Regeneration. Advanced Materials Technologies 2025, 3 https://doi.org/10.1002/admt.202402054
- Wei Qian, Zhuang Li, Jingyao Han, Ye Tian, Zhongwei Niu. Functionalization of rod-shaped plant viruses for biomedical applications. Nanoscale 2025, 5 https://doi.org/10.1039/D4NR05354K
- Sheng‐Jie Shiue, Ming‐Shun Wu, Yi‐Hsien Chiang, Hsin‐Yi Lin. Bacteriophage‐cocktail hydrogel dressing to prevent multiple bacterial infections and heal diabetic ulcers in mice. Journal of Biomedical Materials Research Part A 2024, 112
(11)
, 1846-1859. https://doi.org/10.1002/jbm.a.37728
- Juliane Schuphan, Natalija Stojanović, Ying‐Ying Lin, Eva Miriam Buhl, Sanja Aveic, Ulrich Commandeur, Stefan Schillberg, Horst Fischer. A Combination of Flexible Modified Plant Virus Nanoparticles Enables Additive Effects Resulting in Improved Osteogenesis. Advanced Healthcare Materials 2024, 13
(16)
https://doi.org/10.1002/adhm.202304243
- Jialun Zhang, Haobo He, Fanmeng Zeng, Mingming Du, Dehua Huang, Guangcun Chen, Qiangbin Wang. Advances of Structural Design and Biomedical Applications of Tobacco Mosaic Virus Coat Protein. Advanced NanoBiomed Research 2024, 4
(5)
https://doi.org/10.1002/anbr.202300135
- Lulu Jin, Zhengwei Mao. Living virus‐based nanohybrids for biomedical applications. WIREs Nanomedicine and Nanobiotechnology 2024, 16
(1)
https://doi.org/10.1002/wnan.1923
- Przemyslaw Jurczak, Slawomir Lach. Hydrogels as Scaffolds in Bone‐Related Tissue Engineering and Regeneration. Macromolecular Bioscience 2023, 23
(11)
https://doi.org/10.1002/mabi.202300152
- Tao Yang, Yingfan Chen, Yajing Xu, Xiangyu Liu, Mingying Yang, Chuanbin Mao. Viruses as biomaterials. Materials Science and Engineering: R: Reports 2023, 153 , 100715. https://doi.org/10.1016/j.mser.2023.100715
- Farah Alwani Azaman, Florence Daubiné, Amélie Lebatard, Margaret E. Brennan Fournet, Declan M. Devine. Chitosan/Hydroxyapatite Scaffolds with P28 as a Promising Osteoinductive Scaffold for Bone Healing Applications. Micro 2023, 3
(1)
, 118-142. https://doi.org/10.3390/micro3010010
- Sougata Ghosh, Thomas J. Webster. Bioinspired advanced nanomaterials for infection control and promotion of bone growth. 2023, 161-187. https://doi.org/10.1016/B978-0-12-818627-5.00011-7
- Fania Geiger, Tim Wendlandt, Tim Berking, Joachim P. Spatz, Christina Wege. Convenient site-selective protein coupling from bacterial raw lysates to coenzyme A-modified tobacco mosaic virus (TMV) by Bacillus subtilis Sfp phosphopantetheinyl transferase. Virology 2023, 578 , 61-70. https://doi.org/10.1016/j.virol.2022.11.013
- Xindie He, Masahiro Yamada, Jun Watanabe, Watcharaphol Tiskratok, Minoru Ishibashi, Hideki Kitaura, Itaru Mizoguchi, Hiroshi Egusa. Titanium nanotopography induces osteocyte lacunar-canalicular networks to strengthen osseointegration. Acta Biomaterialia 2022, 151 , 613-627. https://doi.org/10.1016/j.actbio.2022.08.023
- Jutathip Panchamanee, Chavee Laomeephol, Jittima Amie Luckanagul, Qian Wang, Siriporn Damrongsakkul. In vitro biological activities of the flexible and virus nanoparticle-decorated silk fibroin-based films. International Journal of Biological Macromolecules 2022, 216 , 437-445. https://doi.org/10.1016/j.ijbiomac.2022.07.011
- Aunjida Chawanarojnarit, Nirada Dhanesuan, Jittima Amie Luckanagul, Sorasun Rungsiyanont. Biocompatibility study of tobacco mosaic virus nanoparticles on human alveolar bone cells. Journal of Oral Biology and Craniofacial Research 2022, 12
(3)
, 363-369. https://doi.org/10.1016/j.jobcr.2022.04.005
- Ada I Frías-Sánchez, Diego A Quevedo-Moreno, Mohamadmahdi Samandari, Jorge A Tavares-Negrete, Víctor Hugo Sánchez-Rodríguez, Ivonne González-Gamboa, Fernando Ponz, Mario M Alvarez, Grissel Trujillo-de Santiago. Biofabrication of muscle fibers enhanced with plant viral nanoparticles using surface chaotic flows. Biofabrication 2021, 13
(3)
, 035015. https://doi.org/10.1088/1758-5090/abd9d7
- Dehui Fan, Hengping Liu, Zhenning Zhang, Meiyi Su, Zhixian Yuan, Ying Lin, Shuquan Yang, Wenqiang Li, Xintao Zhang. Resveratrol and Angiogenin-2 Combined With PEGDA/TCS Hydrogel for the Targeted Therapy of Hypoxic Bone Defects via Activation of the Autophagy Pathway. Frontiers in Pharmacology 2021, 12 https://doi.org/10.3389/fphar.2021.618724
- Feng Zhao, Guihua Li, Xingxiang Ji, Yingjuan Fu, Menghua Qin, Zaiwu Yuan. Mechano-optical response of micellar hydrogel films. Applied Surface Science 2021, 539 , 148228. https://doi.org/10.1016/j.apsusc.2020.148228
- Christina Dickmeis, Louisa Kauth, Ulrich Commandeur. From infection to healing: The use of plant viruses in bioactive hydrogels. WIREs Nanomedicine and Nanobiotechnology 2021, 13
(1)
https://doi.org/10.1002/wnan.1662
- Ying‐Ying Lin, Juliane Schuphan, Christina Dickmeis, Eva Miriam Buhl, Ulrich Commandeur, Horst Fischer. Attachment of Ultralow Amount of Engineered Plant Viral Nanoparticles to Mesenchymal Stem Cells Enhances Osteogenesis and Mineralization. Advanced Healthcare Materials 2020, 9
(21)
https://doi.org/10.1002/adhm.202001245
- Kun Zhou, Yihao Zhou, Hongchao Yang, Huile Jin, Yonggang Ke, Qiangbin Wang. Interfacially Bridging Covalent Network Yields Hyperstable and Ultralong Virus‐Based Fibers for Engineering Functional Materials. Angewandte Chemie International Edition 2020, 59
(41)
, 18249-18255. https://doi.org/10.1002/anie.202008670
- Kun Zhou, Yihao Zhou, Hongchao Yang, Huile Jin, Yonggang Ke, Qiangbin Wang. Interfacially Bridging Covalent Network Yields Hyperstable and Ultralong Virus‐Based Fibers for Engineering Functional Materials. Angewandte Chemie 2020, 132
(41)
, 18406-18412. https://doi.org/10.1002/ange.202008670
- Christina Wege, Claudia Koch. From stars to stripes: RNA‐directed shaping of plant viral protein templates—structural synthetic virology for smart biohybrid nanostructures. WIREs Nanomedicine and Nanobiotechnology 2020, 12
(2)
https://doi.org/10.1002/wnan.1591
- Olga V. Sinitsyna, Natalia O. Kalinina, Kara McGeachy, Eric Whale, David Hepworth, Andrew J. Love, Michael E. Taliansky, Igor V. Yaminsky. Interaction between nanocellulose and tobacco mosaic virus-like particles: an atomic force microscopy study. Cellulose 2020, 27
(5)
, 2381-2387. https://doi.org/10.1007/s10570-020-02978-1
- Hamed Amani, Hamidreza Arzaghi, Mehrdad Bayandori, Amin Shiralizadeh Dezfuli, Hamidreza Pazoki‐Toroudi, Abbas Shafiee, Lida Moradi. Controlling Cell Behavior through the Design of Biomaterial Surfaces: A Focus on Surface Modification Techniques. Advanced Materials Interfaces 2019, 6
(13)
https://doi.org/10.1002/admi.201900572
- Iruthayapandi Selestin Raja, Chuntae Kim, Su-Jin Song, Yong Cheol Shin, Moon Sung Kang, Suong-Hyu Hyon, Jin-Woo Oh, Dong-Wook Han. Virus-Incorporated Biomimetic Nanocomposites for Tissue Regeneration. Nanomaterials 2019, 9
(7)
, 1014. https://doi.org/10.3390/nano9071014
- Sabine Eiben, Claudia Koch, Klara Altintoprak, Alexander Southan, Günter Tovar, Sabine Laschat, Ingrid M. Weiss, Christina Wege. Plant virus-based materials for biomedical applications: Trends and prospects. Advanced Drug Delivery Reviews 2019, 145 , 96-118. https://doi.org/10.1016/j.addr.2018.08.011
- Shichen Zhu, Qijuan Yuan, Mingtao Yang, Juan You, Tao Yin, Zhipeng Gu, Yang Hu, Shanbai Xiong. A quantitative comparable study on multi-hierarchy conformation of acid and pepsin-solubilized collagens from the skin of grass carp (Ctenopharyngodon idella). Materials Science and Engineering: C 2019, 96 , 446-457. https://doi.org/10.1016/j.msec.2018.11.043
- Pahweenvaj Ratnatilaka Na Bhuket, Jittima Amie Luckanagul, Pornchai Rojsitthisak, Qian Wang. Chemical modification of enveloped viruses for biomedical applications. Integrative Biology 2018, 10
(11)
, 666-679. https://doi.org/10.1039/C8IB00118A
- Di Wu, Youyan Liang, Kai Huang, Xinyi Jing, Bin Li, Hongshan Liang. Leveraging plant exine capsules as pH-responsive delivery vehicles for hydrophobic nutraceutical encapsulation. Food & Function 2018, 9
(10)
, 5436-5442. https://doi.org/10.1039/C8FO01665H
- Yang Zhang, Guohua Jiang, Weijiang Yu, Depeng Liu, Bin Xu. Microneedles fabricated from alginate and maltose for transdermal delivery of insulin on diabetic rats. Materials Science and Engineering: C 2018, 85 , 18-26. https://doi.org/10.1016/j.msec.2017.12.006
- Yi Zheng, Melissa Lucius Dougherty, Dominik Konkolewicz, Nicole F. Steinmetz, Jonathan K. Pokorski. Green nanofillers: Plant virus reinforcement in hydrophilic polymer nanocomposites. Polymer 2018, 142 , 72-79. https://doi.org/10.1016/j.polymer.2018.03.030
- Liulin Yang, Aijie Liu, Mark V. de Ruiter, Catharina. A. Hommersom, Nathalie Katsonis, Pascal Jonkheijm, Jeroen J. L. M. Cornelissen. Compartmentalized supramolecular hydrogels based on viral nanocages towards sophisticated cargo administration. Nanoscale 2018, 10
(8)
, 4123-4129. https://doi.org/10.1039/C7NR07718A
- Ines Lauria, Christina Dickmeis, Juliane Röder, Malin Beckers, Stephan Rütten, Ying Ying Lin, Ulrich Commandeur, Horst Fischer. Engineered Potato virus X nanoparticles support hydroxyapatite nucleation for improved bone tissue replacement. Acta Biomaterialia 2017, 62 , 317-327. https://doi.org/10.1016/j.actbio.2017.08.039
- Hongshan Liang, Bin Zhou, Jing Li, Yun He, Yaqiong Pei, Bin Li. Engineering functional alginate beads for encapsulation of Pickering emulsions stabilized by colloidal particles. RSC Advances 2016, 6
(103)
, 101267-101276. https://doi.org/10.1039/C6RA21755A
Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.
Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.
The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.