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Design and Evaluation of a High-Precision Programmable Force-Sensing Therapeutic Intramyocardial Stem Cell Injection Device

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Abstract

Treating congestive heart failure by injecting potential cardio-reparative cells, such as mesenchymal stem cells (MSCs), into the myocardium via a needle-tipped catheter is a novel approach that may improve clinical outcomes. While clinical trials vary on cell type, dose, and rate of injection, a typical intramyocardial procedure involves hand injecting 10–16 sequential cell aliquots of up to 0.5 mL volume per aliquot over 30–60 s via a 25 G × 110 cm long injection needle. Unfortunately, manual hand injections can result in unpredictable flow rates and hand fatigue, causing inconsistent cell delivery and thus treatment results. Automating the cell delivery with controlled injection rates that are optimized to ensure cell viability upon exiting the catheter can enhance local cell retention and ultimately therapeutic efficacy. In response to this need, we designed a novel, automated programmable injection device that integrates with for-human-use syringes and transcatheter intramyocardial injection catheters, provides controlled injection rates, and displays injection forces and pressures applied to the injectate in real time. Using MSCs, bovine skeletal muscle of varying stiffness, and ex vivo porcine heart for intramyocardial injection testing, we confirmed that the device prototype reliably delivers 0.5 mL aliquots in 30- and 60-s intervals, accurately and reproducibly, measures force and pressure with real-time feedback, and preserves cell viability without clumping and obstructing the catheter. The novel, automated programmable cell injection device and testing framework we developed has the potential to improve the success of transcatheter intramyocardial delivery for heart repair.

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References

  1. Centers for Disease Control and Prevention: Leading Causes of Death. Centers for Disease Control and Prevention (2019), https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Accessed 13 Feb 2023

  2. G.F. Tomaselli, D.P. Zipes, What causes sudden death in heart failure? Circulation Res. (2004). https://doi.org/10.1161/01.res.0000145047.14691.db

    Article  PubMed  Google Scholar 

  3. Y. Guo, Y. Yu, S. Hu, Y. Chen, Z. Shen, The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death Dis. (2020). https://doi.org/10.1038/s41419-020-2542-9

    Article  PubMed  PubMed Central  Google Scholar 

  4. M. Fan, Y. Huang, Z. Chen, Y. Xia, A. Chen, D. Lu, Y. Wu, N. Zhang, J. Qian, Efficacy of mesenchymal stem cell therapy in systolic heart failure: a systematic review and meta-analysis. Stem Cell Res. Ther. (2019). https://doi.org/10.1186/s13287-019-1258-1

    Article  PubMed  PubMed Central  Google Scholar 

  5. M.H. Amer, F.R.A.J. Rose, L.J. White, K.M. Shakesheff, A detailed assessment of varying ejection rate on delivery efficiency of mesenchymal stem cells using narrow-bore needles. Stem Cells Transl. Med. (2016). https://doi.org/10.5966/sctm.2015-0208

    Article  PubMed  PubMed Central  Google Scholar 

  6. A.N. Raval et al., Point of care, bone marrow mononuclear cell therapy in ischemic heart failure patients personalized for cell potency: 12-month feasibility results from cardiAMP heart failure roll-in cohort. Int. J. Cardiol. (2021). https://doi.org/10.1016/j.ijcard.2020.10.043

    Article  PubMed  Google Scholar 

  7. R. Emig, C.M. Zgierski-Johnston, V. Timmermann, A.J. Taberner, M.P. Nash, P. Kohl, R. Peyronnet, Passive myocardial mechanical properties: meaning, measurement. Models. Biophys. Rev. (2021). https://doi.org/10.1007/s12551-021-00838-1

    Article  PubMed  Google Scholar 

  8. I. Allijn, M. Ribeiro, A. Poot, R. Passier, D. Stamatialis, Membranes for modeling cardiac tissue stiffness in vitro based on poly(trimethylene carbonate) and poly(ethylene glycol) polymers. Membranes (2020). https://doi.org/10.3390/membranes10100274

    Article  PubMed  PubMed Central  Google Scholar 

  9. E. Schmuck et al., Intravenous followed by x-ray fused with MRI-guided transendocardial mesenchymal stem cell injection improves contractility reserve in a swine model of myocardial infarction. J. Cardiovasc. Transl. Res. (2015). https://doi.org/10.1007/s12265-015-9654-0

    Article  PubMed  PubMed Central  Google Scholar 

  10. B. James, S.W. Yang, Testing meat tenderness using an In Situ straining stage with variable pressure scanning electron microscopy. Procedia Food Sci. (2011). https://doi.org/10.1016/j.profoo.2011.09.041

    Article  Google Scholar 

  11. S. Ramadan, N. Paul, H.E. Naguib, Dynamic and static tensile mechanical properties of myocardial tissue. Front. Bioeng. Biotechnol. (2016). https://doi.org/10.3389/conf.fbioe.2016.01.00501

    Article  Google Scholar 

  12. P.P. Lelovas, N.G. Kostomitsopoulos, T.T. Xanthos, A comparative anatomic and physiologic overview of the porcine heart. J. Am. Assoc. Lab. Anim. Sci. 53(5), 432–438 (2014)

    CAS  PubMed  PubMed Central  Google Scholar 

  13. E.C. Perin et al., Transendocardial, autologous bone marrow cell transplantation for severe chronic ischemic heart failure. Circulation (2003). https://doi.org/10.1161/01.CIR.0000070596.30552.8B

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to acknowledge Dr. Aviad Hai for all of his guidance and assistance with the design process. The authors would also like to thank the Biomedical Engineering Design staff at the University of Wisconsin-Madison for this opportunity. This work was supported by a Wisconsin State Economic Engagement and Development (SEED) Research Program Grant.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA

    Parker J. Esswein, Macy C. Frank, Vanessa J. Obrycki, Lars S. Krugel & Gabrielle N. Zuern

  2. Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA

    Eric G. Schmuck & Amish N. Raval

  3. Department of Medicine and Department of Biomedical Engineering (Affiliate), University of Wisconsin-Madison, Madison, USA

    Amish N. Raval

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  1. Parker J. Esswein
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  2. Macy C. Frank
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  4. Lars S. Krugel
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  5. Gabrielle N. Zuern
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  6. Eric G. Schmuck
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  7. Amish N. Raval
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Correspondence to Amish N. Raval.

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Conflict of interest

ANR is a consultant for Novo Nordisk and Blue Rock Therapeutics. He is a founder with equity share of Cellular Logistics. He receives clinical trial research support from BioCardia Inc. EGS is a founder with equity share from Cellular Logistics.

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Esswein, P.J., Frank, M.C., Obrycki, V.J. et al. Design and Evaluation of a High-Precision Programmable Force-Sensing Therapeutic Intramyocardial Stem Cell Injection Device. Biomedical Materials & Devices (2024). https://doi.org/10.1007/s44174-024-00175-3

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