Research Article

Acellular collagen–glycosaminoglycan matrix promotes functional recovery in a rat model of volumetric muscle loss

https://orcid.org/0000-0003-3839-0844

Division of Plastic Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX 79430, USA

‡Authors contributed equally

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Mehran Karvar‡

Division of Plastic Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

‡Authors contributed equally

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Daniel J Koh

https://orcid.org/0000-0003-3007-8223

Division of Plastic Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

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Karina Sklyar

Division of Plastic Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

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Yori Endo

Division of Plastic Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

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Jacob Quint

Department of Biomedical Engineering, University of Connecticut, Farmington, CT 06269, USA

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Mohamadmahdi Samandari

Department of Biomedical Engineering, University of Connecticut, Farmington, CT 06269, USA

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Ali Tamayol

Department of Biomedical Engineering, University of Connecticut, Farmington, CT 06269, USA

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Indranil Sinha

*Author for correspondence:

E-mail Address: isinha@bwh.harvard.edu

https://orcid.org/0000-0001-9494-6523

Division of Plastic Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

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Published Online:25 Jul 2023https://doi.org/10.2217/rme-2023-0060

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Abstract

Aim: Volumetric muscle loss (VML) is a composite loss of skeletal muscle, which heals with fibrosis, minimal muscle regeneration, and incomplete functional recovery. This study investigated whether collagen–glycosaminoglycan scaffolds (CGS) improve functional recovery following VML. Methods: 15 Sprague-Dawley rats underwent either sham injury or bilateral tibialis anterior (TA) VML injury, with or without CGS implantation. Results: In rats with VML injuries treated with CGS, the TA exhibited greater in vivo tetanic forces and in situ twitch and tetanic dorsiflexion forces compared with those in the non-CGS group at 4- and 6-weeks following injury, respectively. Histologically, the VML with CGS group demonstrated reduced fibrosis and increased muscle regeneration. Conclusion: Taken together, CGS implantation has potential augment muscle recovery following VML.

Plain language summary

Volumetric muscle loss (VML) is a large injury to skeletal muscle. VML heals with scarring, little muscle regeneration, and incomplete strength recovery. The current treatment for VML involves transferring muscle from one part of the body to the injury site. However, this is limited by weakness of the donor site and incomplete recovery of muscle function. Therefore, other treatments have been developed to aid in muscle healing. One such treatment involves using three dimensional templates, known as scaffolds, to aid in muscle regeneration. Our goal is to determine whether a collagen–glycosaminoglycan scaffold (CGS), which is already used for other medical purposes, can improve healing of VML injuries in rats. CGS placement in rat muscle injuries resulted in decreased scarring, increased muscle regeneration, and increased strength recovery compared with the non-CGS group.

Tweetable abstract

Acellular collagen–glycosaminoglycan scaffolds promote functional recovery, reduced fibrosis and increased muscle regeneration in a rat model of volumetric muscle loss.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 18, No. 8

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History

Received 5 April 2023

Accepted 28 June 2023

Published online 25 July 2023

Published in print August 2023

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Keywords

Author contributions

M Karvar, Y Endo and I Sinha conceived the idea. The experiments were designed by M Karvar and I Sinha. The experiments were conducted by M Karvar, C Zhu, D Koh. All the authors assisted with the data analysis and interpretation of the results. The manuscript was written by C Zhu, D Koh, K Sklyar and I Sinha. All the authors assisted with manuscript revision.

Financial & competing interests disclosure

The authors certify that financial and/or material support was provided for this research and/or the creation of this work by Integra LifeSciences. Mohamadmahdi Samandari, Jacob Quint, Ali Tamayol and Indranil Sinha report a relationship with InPrint Bio LLC that includes equity or stocks. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

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