Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration

Yumeng Xue; Han Jun Kim; Junmin Lee; Yaowen Liu; Tyler Hoffman; Yi Chen; Xingwu Zhou; Wujin Sun; Shiming Zhang; Hyun Jong Cho; Ji Yong Lee; Heemin Kang; Won Hyoung Ryu; Chang Moon Lee; Samad Ahadian; Mehmet R. Dokmeci; Bo Lei; Kang Ju Lee; Ali Khademhosseini

doi:10.1002/smll.202107714

Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration

Yumeng Xue, Han Jun Kim, Junmin Lee, Yaowen Liu, Tyler Hoffman, Yi Chen, Xingwu Zhou, Wujin Sun, Shiming Zhang, Hyun Jong Cho, Ji Yong Lee, Heemin Kang, Won Hyoung Ryu, Chang Moon Lee, Samad Ahadian, Mehmet R. Dokmeci, Bo Lei, Kang Ju Lee, Ali Khademhosseini

Department of Mechanical Engineering

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its application in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) is combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers can be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibit enhanced growth, proliferation, vascular endothelial growth factor production, and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds can greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis-related immunofluorescence staining indicate SG7 scaffolds demonstrate enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.

Original language	English
Article number	2107714
Journal	Small
Volume	18
Issue number	21
DOIs	https://doi.org/10.1002/smll.202107714
Publication status	Published - 2022 May 26

Bibliographical note

Funding Information:
Y.X. and H.-J.K. contributed equally to this work. The authors also acknowledge the startup fund from the University of California, Los Angeles, fund from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1F1A105502211), National Natural Science Foundation of China (52103320), and the Fundamental Research Funds for the Central Universities (G2021KY05102). Y.X. acknowledge the support from China Scholarship Council.

Funding Information:
Y.X. and H.‐J.K. contributed equally to this work. The authors also acknowledge the startup fund from the University of California, Los Angeles, fund from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1F1A105502211), National Natural Science Foundation of China (52103320), and the Fundamental Research Funds for the Central Universities (G2021KY05102). Y.X. acknowledge the support from China Scholarship Council.

Publisher Copyright:
© 2022 Wiley-VCH GmbH.

All Science Journal Classification (ASJC) codes

Biotechnology
Chemistry(all)
Biomaterials
Materials Science(all)

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10.1002/smll.202107714

Cite this

Xue, Y., Kim, H. J., Lee, J., Liu, Y., Hoffman, T., Chen, Y., Zhou, X., Sun, W., Zhang, S., Cho, H. J., Lee, J. Y., Kang, H., Ryu, W. H., Lee, C. M., Ahadian, S., Dokmeci, M. R., Lei, B., Lee, K. J., & Khademhosseini, A. (2022). Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration. Small, 18(21), [2107714]. https://doi.org/10.1002/smll.202107714

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title = "Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration",

abstract = "Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its application in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) is combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers can be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibit enhanced growth, proliferation, vascular endothelial growth factor production, and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds can greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis-related immunofluorescence staining indicate SG7 scaffolds demonstrate enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.",

author = "Yumeng Xue and Kim, {Han Jun} and Junmin Lee and Yaowen Liu and Tyler Hoffman and Yi Chen and Xingwu Zhou and Wujin Sun and Shiming Zhang and Cho, {Hyun Jong} and Lee, {Ji Yong} and Heemin Kang and Ryu, {Won Hyoung} and Lee, {Chang Moon} and Samad Ahadian and Dokmeci, {Mehmet R.} and Bo Lei and Lee, {Kang Ju} and Ali Khademhosseini",

note = "Funding Information: Y.X. and H.-J.K. contributed equally to this work. The authors also acknowledge the startup fund from the University of California, Los Angeles, fund from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1F1A105502211), National Natural Science Foundation of China (52103320), and the Fundamental Research Funds for the Central Universities (G2021KY05102). Y.X. acknowledge the support from China Scholarship Council. Funding Information: Y.X. and H.‐J.K. contributed equally to this work. The authors also acknowledge the startup fund from the University of California, Los Angeles, fund from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1F1A105502211), National Natural Science Foundation of China (52103320), and the Fundamental Research Funds for the Central Universities (G2021KY05102). Y.X. acknowledge the support from China Scholarship Council. Publisher Copyright: {\textcopyright} 2022 Wiley-VCH GmbH.",

year = "2022",

month = may,

day = "26",

doi = "10.1002/smll.202107714",

language = "English",

volume = "18",

journal = "Small",

issn = "1613-6810",

publisher = "Wiley-VCH Verlag",

number = "21",

}

Xue, Y, Kim, HJ, Lee, J, Liu, Y, Hoffman, T, Chen, Y, Zhou, X, Sun, W, Zhang, S, Cho, HJ, Lee, JY, Kang, H, Ryu, WH, Lee, CM, Ahadian, S, Dokmeci, MR, Lei, B, Lee, KJ & Khademhosseini, A 2022, 'Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration', Small, vol. 18, no. 21, 2107714. https://doi.org/10.1002/smll.202107714

TY - JOUR

T1 - Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration

AU - Xue, Yumeng

AU - Kim, Han Jun

AU - Lee, Junmin

AU - Liu, Yaowen

AU - Hoffman, Tyler

AU - Chen, Yi

AU - Zhou, Xingwu

AU - Sun, Wujin

AU - Zhang, Shiming

AU - Cho, Hyun Jong

AU - Lee, Ji Yong

AU - Kang, Heemin

AU - Ryu, Won Hyoung

AU - Lee, Chang Moon

AU - Ahadian, Samad

AU - Dokmeci, Mehmet R.

AU - Lei, Bo

AU - Lee, Kang Ju

AU - Khademhosseini, Ali

N1 - Funding Information: Y.X. and H.-J.K. contributed equally to this work. The authors also acknowledge the startup fund from the University of California, Los Angeles, fund from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1F1A105502211), National Natural Science Foundation of China (52103320), and the Fundamental Research Funds for the Central Universities (G2021KY05102). Y.X. acknowledge the support from China Scholarship Council. Funding Information: Y.X. and H.‐J.K. contributed equally to this work. The authors also acknowledge the startup fund from the University of California, Los Angeles, fund from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1F1A105502211), National Natural Science Foundation of China (52103320), and the Fundamental Research Funds for the Central Universities (G2021KY05102). Y.X. acknowledge the support from China Scholarship Council. Publisher Copyright: © 2022 Wiley-VCH GmbH.

PY - 2022/5/26

Y1 - 2022/5/26

N2 - Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its application in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) is combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers can be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibit enhanced growth, proliferation, vascular endothelial growth factor production, and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds can greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis-related immunofluorescence staining indicate SG7 scaffolds demonstrate enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.

AB - Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its application in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) is combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers can be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibit enhanced growth, proliferation, vascular endothelial growth factor production, and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds can greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis-related immunofluorescence staining indicate SG7 scaffolds demonstrate enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.

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U2 - 10.1002/smll.202107714

DO - 10.1002/smll.202107714

M3 - Article

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AN - SCOPUS:85128901323

SN - 1613-6810

VL - 18

JO - Small

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ER -

Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration

Abstract

Bibliographical note

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