Development of printable and cell compatible bioink for 3D bioprinting of skeletal muscle tissue

Despite the high capacity of self-regenerating in the skeletal muscle, when a significant loss of tissue occurs, it results in severe loss of function. Therefore, in our group, we focus on the combination of biomaterials and microtechnologies to engineer functional skeletal muscle tissue. 

This project is funded since 2018 and we are currently in the third funding period (2026-2029) by DFG (Deutsche Forschungsgemeinschaft) as a TRR-SFB 225 consortium- subproject B03 entitled “Biofabrication of perfusable skeletal muscle tissue and cellular biomechanic analysis”. The project is in collaboration with Prof. Boccaccini from Friedrich-Alexander University of Erlangen-Nuremberg, Institute of Biomaterials, Prof. Frank Döpper from the University of Bayreuth, Chair Manufacturing and Remanufacturing Technology and Prof. Ada Cavalcanti-Adam, Chair of Cellular Biomechanic.

In the first funding period (2018-2021), as subproject B03 entitled “Simultaneous printing and biofabrication of skeletal muscle tissue and bioreactor”, we developed composite inks which supported the formation of anisotropic tissue models like skeletal model. Simultaneous printing of the bioreactor and the 3D printed tissue model supported the fabrication of a patient-specific tissue model with a compatible design for potential clinical applications. The project was in collaboration with Prof. Boccaccini from Friedrich-Alexander University of Erlangen-Nuremberg, Institute of Biomaterials, and Prof. Jan Hansmann from the University of applied sciences Würzburg-Schweinfurt.

In the second funding period (2022-2025), as subproject B03 entitled “Printing of biofabricate and customized bioreactors for skeletal muscle tissue”, we developed composite inks containing bioactive fillers and electrically conductive ones which supported the formation of anisotropic tissue models like skeletal model. Additively manufactured bioreactor with multifunctionality was developed for dynamic culture and electrical stimualtion of the 3D printed tissue model. The project was in collaboration with Prof. Boccaccini from Friedrich-Alexander University of Erlangen-Nuremberg, Institute of Biomaterials, and Prof. Frank Döpper from the University of Bayreuth.

In the published works out of this project, we showed the design and 3D printing of the bioreactors for the dynamic culture of the cell encapsulated 3D printed bioinks. Furthermore, gelatin-based bioink were tested for long-term culture of the skeletal muscle cells as well as angiogenesis after four weeks of culture in intravital microscopy in the AV-loop rat model. The gelatin-based hydrogel supported the formation of the first sprout of the vessels and their distribution within the 3D hydrogel in comparison with controls such as fibrin.

Further information can be found on the TRR-SFB 225 Biofabrication homepage

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• S. Heilig, Z. Lamberger, L. Sprenger, V. Priebe,  C. Mussoni,  D. Docheva,  K. Andelovic,  J. Groll,  S. Salehi,  G. Lang,  M. Ryma, Fibrillar Bundles as Fibrous Filler Materials for Attaining Cell Anisotropy in Bioprinting. Adv. Healthcare Mater. 2025: e03767. https://doi.org/10.1002/adhm.202503767
  
  
• L. Sprenger, H.-H. Lu, S. Trippmacher, U. Mansfeld, P. Milkin, L. Ionov, G. Papastavrou, A.R. Boccaccini, S. Salehi, Composite Alginate Dialdehyde-Gelatin (ADA-GEL) Hydrogel Containing Short Ribbon-Shaped Fillers for Skeletal Muscle Tissue Biofabrication, ACS Applied Materials and Interfaces;  2024 , https://doi.org/10.1021/acsami.4c10751
  
  
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• R. Vaghela R, A. Arkudas, D. Gage, C. Körner, S. Von Hörsten, S. Salehi, R.E. Horch, M. Hessenauer, A novel window into angiogenesis - intravital microscopy in the AV-Loop-model, Cells, 2023, 12, 261.
  
  
• M. Gensler, C. Malkmus, P. Ockermann, M. Möllmann, L. Hahn, S. Salehi, R. Luxenhofer, A.R. Boccaccini, J. Hansmann, Perfusable tissue bioprinted into a 3D-printed tailored bioreactor system, Bioengineering 2024, 11(1), 68.
  
  
• T. Gruhn, C. Ortiz-Monsalve, C. Müller, S. Heid, A.R. Boccaccini, S. Salehi*,  Fabrication of hydrogel-based composite fibers and computer simulation of the filler dynamics in the composite flow, Bioengineering 2023 10 (4), 448.
  
  
• T. Gruhn, C. Ortiz-Monsalve, S. Salehi, Structure formation of rod-like fillers in a contraction flow, Physics of Fluids, 2023, 35, 043107.
  
  
• J. Schulik, S. Salehi, A.R.Boccaccini, S. Schrüfer, D.W. Schubert, A. Arkudas, A. Kengelbach-Weigand, R.E. Horch, R. Schmid, Comparison of the behavior of 3D-printed endothelial cells in different bioinks, Bioengineering 2023, 10, 751.
  
  
• M. Gensler, A. Leikeim, M. Möllmann, M. Komma, S. Heid, C. Müller, A. R. Boccaccini, S. Salehi, F. Groeber-Becker, J. Hansmann, 3D printing of bioreactors in tissue engineering: A generalised approach, PLOS ONE 2020 15(11): e0242615.
  
  
• C. Müller, M. Trujillo-Miranda, M. Maier, D. E Heath, A. O'Connor, S. Salehi, Effects of External Stimulators on Engineered Skeletal Muscle Tissue Maturation, Adv. Mater. Interfaces 2021, 8, 2001167.
  
  
• C.S. Russell, A. Mostafavi, J. P. Quint, A. Panayi, K. Udeh, T. J. Williams, J. G. Daubendiek, V. Hugo Sánchez, Z. Bonick, M. Trujillo-Miranda, S. Ryon Shin, O. Pourquie, S. Salehi, I. Sinha, and A. Tamayol, In Situ Printing of Adhesive Hydrogel Scaffolds for the Treatment of Skeletal Muscle Injuries, ACS Appl. Biomater. 2020, 3, 3, 1568-1579.
  
  
• S. Ostrovidov, S. Salehi, M. Costantini, K. Suthiwanish, M. Ebrahimi, R. B. Sadeghian, T. Fujie, X. Shi, S. Cannata, C. Gargioli, A. Tamayol, M. R. Dokmeci, G. Orive, W. Swieszkowski, A. Khademhosseini, 3D Bioprinting in Skeletal Muscle, Small 2019, 15 (24), 1805530.
  
  
• S. Heltmann-Meyer, D. Steiner, C. Müller, D. Schneidereit, O. Friedrich, S. Salehi, F. B. Engel, A. Arkudas, R. E. Horch, Gelatin methacryloyl is a slow degrading material allowing vascularization and long-term use in vivo, Biomed. Mater. 2021 16 065004.
  
  
• M. Hessenauer, R. Vaghela, C. Körner, S. v. Hörsten, C. Pobel, D. Gage, C. Müller, S. Salehi, R. E. Horch, A. Arkudas, Watching the vessels grow – establishment of intravital microscopy in the AV-loop rat model, Tissue Engineering Part C: Methods 2021 27:6, 357-365.

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• R. Vaghela, A. Arkudas, D. Gage, C. Körner, S. Von Hörsten, S. Salehi, R.E. Horch, M. Hessenauer, A novel window into angiogenesis - intravital microscopy in the AV-Loop-model, Cells, 2023, 12, 261.