Harnessing nerve–muscle cell interactions for biomaterials-based skeletal muscle regeneration
Naagarajan Narayanan
Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, Indiana, USA
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorPaul Lengemann
Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, Indiana, USA
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorKun Ho Kim
Department of Animal Science, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorLiangju Kuang
Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, Indiana, USA
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorTiago Sobreira
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorVictoria Hedrick
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorUma K. Aryal
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorShihuan Kuang
Department of Animal Science, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorCorresponding Author
Meng Deng
Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, Indiana, USA
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
School of Materials Engineering, Purdue University, West Lafayette, Indiana, USA
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
Correspondence
Meng Deng, Department of Agricultural and Biological Engineering, School of Materials Engineering, Weldon School of Biomedical Engineering, Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907-2093.
Email: [email protected]
Search for more papers by this authorNaagarajan Narayanan
Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, Indiana, USA
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorPaul Lengemann
Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, Indiana, USA
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorKun Ho Kim
Department of Animal Science, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorLiangju Kuang
Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, Indiana, USA
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorTiago Sobreira
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorVictoria Hedrick
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorUma K. Aryal
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorShihuan Kuang
Department of Animal Science, Purdue University, West Lafayette, Indiana, USA
Search for more papers by this authorCorresponding Author
Meng Deng
Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, Indiana, USA
Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA
School of Materials Engineering, Purdue University, West Lafayette, Indiana, USA
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
Correspondence
Meng Deng, Department of Agricultural and Biological Engineering, School of Materials Engineering, Weldon School of Biomedical Engineering, Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907-2093.
Email: [email protected]
Search for more papers by this authorFunding information: National Institutes of Health, Grant/Award Number: R03AR068108; Purdue Startup Package
Abstract
Nerve cells secrete neurotrophic factors that play a critical role in neuronal survival, proliferation, and regeneration. However, their role in regulating myoblast behavior and skeletal muscle repair remains largely unexplored. In the present study, we investigated the effects of PC12 secreted signaling factors in modulating C2C12 myoblast behavior under physiologically relevant conditions. We showed that PC12 conditioned media modulated myoblast proliferation and differentiation in both 2D culture and 3D aligned electrospun fiber scaffold system in a dose-dependent manner. We further developed a biomimetic, tunable hydrogel consisting of hyaluronic acid, chondroitin sulfate, and polyethylene glycol as a 3D matrix encapsulating PC12 cells. The hydrogel-encapsulated PC12 cells promoted survival and proliferation of myoblasts in co-culture. Further proteomics analysis identified a total of 2,088 proteins from the secretome of the encapsulated PC12 cells and revealed the biological role and overlapping functions of nerve-secreted proteins for skeletal muscle regeneration, potentially through regulating myoblast behavior, nerve function, and angiogenesis. These experiments provide insights into the nerve–muscle interactions and pave the way for developing advanced biomaterials strategies incorporating nerve cell secretome for accelerated skeletal muscle regeneration.
Supporting Information
| Filename | Description |
|---|---|
| jbma37022-sup-0001-supinfo.docxWord 2007 document , 8.3 MB | Appendix S1: Supporting information. |
| jbma37022-sup-0001-TableS2.docxWord 2007 document , 470.8 KB | Table S2 MaxQuant search engine output for 5 M group. |
| jbma37022-sup-0002-TableS3.docxWord 2007 document , 227.1 KB | Table S3 List of filtered peptides. |
| jbma37022-sup-0003-TableS4.docxWord 2007 document , 36.1 KB | Table S4 List of SignalP predicted peptides. |
| jbma37022-sup-0004-TableS5.docxWord 2007 document , 26.4 KB | Table S5 List of DeepLoc predicted peptides. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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