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Regenerative Engineering of a Limb: From Amputation to Regeneration

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Abstract

Purpose

This work is a summary of regeneration mechanisms and some important aspects of cellular and molecular factors in regeneration, in addition to techniques that have been employed for limb regeneration.

Methods

In this article, a comprehensive review of literature related to limb regeneration mechanisms, influential factors in limb regeneration, and limb regeneration strategies has been conducted.

Results

Regeneration mechanism in regenerative species is different from mammals and blastema formation after wound healing helps them to regrow their limb. Also, some essential signaling pathways should be activated for proper regeneration. Moreover, age, immune system, metamorphosis, and body size are critical parameters that can influence regeneration in different species. Several approaches are being studied to promote limb regeneration including cell therapy, gene therapy, immune-based therapy, and electrical stimulation, but none of them led to complete limb regeneration. Regenerative engineering is an emerging multi-disciplinary field for the reconstruction of complex tissues and organ systems, making it a viable approach for the regeneration of limbs as well.

Conclusion

Despite significant advances in the field leading to a better understanding of the mechanisms and parameters involved in regeneration, the specific techniques and approaches for successfully regenerating limbs in mammals have yet to be discovered. We believe solutions lie in using a convergence of technologies and regenerative engineering is the central approach for human limb regeneration.

Lay Summary

Limb loss is experienced by more than 2 million Americans, negatively impacting their quality of life. It has been determined that mammals, including humans, can only regenerate certain tissues, such as digit tips. However, regenerative amphibians are capable of fully regenerating their limbs. Therefore, taking clues from urodeles, research on developing techniques, and studying mechanisms to regenerate human limbs is becoming a highly important field pursued vigorously. In this review, we first explain the process of limb regeneration in urodele amphibians followed by important factors affecting regeneration. Next, we explain the present strategies and methods for mammalian limb regeneration.

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Acknowledgements

We thank Dr. Debolina Ghosh for her helpful insights and for editing this manuscript. Original images were created using Biorender.

Funding

This work is supported by NIH/NIAMS T32AR079114 (to CTL), NIH Building Infrastructure to Diversity (BUILD) TL4GM118971 and funding from Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences.

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Authors and Affiliations

  1. The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT, 06030, USA

    Amir Abbas Abedini, Fatemeh Hosseini & Cato T. Laurencin

  2. Biological, Physical and Engineering Sciences, Raymond and Beverly Sackler Center for Biomedical, UConn Health, Farmington, CT, 06030, USA

    Amir Abbas Abedini, Fatemeh Hosseini & Cato T. Laurencin

  3. Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, 06269, USA

    Amir Abbas Abedini & Cato T. Laurencin

  4. Department of Orthopedic Surgery, UConn Health, Farmington, CT, 06030, USA

    Fatemeh Hosseini & Cato T. Laurencin

  5. Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA

    Cato T. Laurencin

  6. Department of Chemical and Bimolecular Engineering, University of Connecticut, Storrs, CT, 06269, USA

    Cato T. Laurencin

Authors
  1. Amir Abbas Abedini
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  2. Fatemeh Hosseini
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  3. Cato T. Laurencin
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Contributions

Amir Abbas Abedini contributed to writing, conception, and figure preparation. Fatemeh Hosseini contributed to writing and figure preparation. The corresponding author of this work is Dr. Cato T. Laurencin, who also oversaw the drafting of the manuscript.

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Correspondence to Cato T. Laurencin.

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Description of Future Works

Future research should focus on employing regenerative engineering to regenerate a limb and conducting appropriate in vitro and in vivo studies to demonstrate the efficiency of this approach.

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Abedini, A.A., Hosseini, F. & Laurencin, C.T. Regenerative Engineering of a Limb: From Amputation to Regeneration. Regen. Eng. Transl. Med. (2023). https://doi.org/10.1007/s40883-023-00323-z

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