Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment
Tendon mechanical properties are significantly compromised in adult tendon injuries, tendon-related birth defects, and connective tissue disorders. Unfortunately, there currently is no effective treatment to restore native tendon mechanical properties after postnatal tendon injury or abnormal fetal...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.945639/full |
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| author | Phong K. Nguyen Phong K. Nguyen Aniket Jana Chi Huang Alison Grafton Iverson Holt Michael Giacomelli Catherine K. Kuo Catherine K. Kuo Catherine K. Kuo Catherine K. Kuo Catherine K. Kuo |
| author_facet | Phong K. Nguyen Phong K. Nguyen Aniket Jana Chi Huang Alison Grafton Iverson Holt Michael Giacomelli Catherine K. Kuo Catherine K. Kuo Catherine K. Kuo Catherine K. Kuo Catherine K. Kuo |
| author_sort | Phong K. Nguyen |
| collection | DOAJ |
| description | Tendon mechanical properties are significantly compromised in adult tendon injuries, tendon-related birth defects, and connective tissue disorders. Unfortunately, there currently is no effective treatment to restore native tendon mechanical properties after postnatal tendon injury or abnormal fetal development. Approaches to promote crosslinking of extracellular matrix components in tendon have been proposed to enhance insufficient mechanical properties of fibrotic tendon after healing. However, these crosslinking agents, which are not naturally present in the body, are associated with toxicity and significant reductions in metabolic activity at concentrations that enhance tendon mechanical properties. In contrast, we propose that an effective method to restore tendon mechanical properties would be to promote lysyl oxidase (LOX)-mediated collagen crosslinking in tendon during adult tissue healing or fetal tissue development. LOX is naturally occurring in the body, and we previously demonstrated LOX-mediated collagen crosslinking to be a critical regulator of tendon mechanical properties during new tissue formation. In this study, we examined the effects of recombinant LOX treatment on tendon at different stages of development. We found that recombinant LOX treatment significantly enhanced tensile and nanoscale tendon mechanical properties without affecting cell viability or collagen content, density, and maturity. Interestingly, both tendon elastic modulus and LOX-mediated collagen crosslink density plateaued at higher recombinant LOX concentrations, which may have been due to limited availability of adjacent lysine residues that are near enough to be crosslinked together. The plateau in crosslink density at higher concentrations of recombinant LOX treatments may have implications for preventing over-stiffening of tendon, though this requires further investigation. These findings demonstrate the exciting potential for a LOX-based therapeutic to enhance tendon mechanical properties via a naturally occurring crosslinking mechanism, which could have tremendous implications for an estimated 32 million acute and chronic tendon and ligament injuries each year in the U.S. |
| first_indexed | 2024-12-10T17:08:45Z |
| format | Article |
| id | doaj.art-cace7fd91ff74ba4baf8e14f6c61669f |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-10T17:08:45Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-cace7fd91ff74ba4baf8e14f6c61669f2022-12-22T01:40:23ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-08-011010.3389/fbioe.2022.945639945639Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatmentPhong K. Nguyen0Phong K. Nguyen1Aniket Jana2Chi Huang3Alison Grafton4Iverson Holt5Michael Giacomelli6Catherine K. Kuo7Catherine K. Kuo8Catherine K. Kuo9Catherine K. Kuo10Catherine K. Kuo11Department of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United StatesFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesDepartment of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesDepartment of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesDepartment of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United StatesFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesDepartment of Orthopaedics, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, United StatesTendon mechanical properties are significantly compromised in adult tendon injuries, tendon-related birth defects, and connective tissue disorders. Unfortunately, there currently is no effective treatment to restore native tendon mechanical properties after postnatal tendon injury or abnormal fetal development. Approaches to promote crosslinking of extracellular matrix components in tendon have been proposed to enhance insufficient mechanical properties of fibrotic tendon after healing. However, these crosslinking agents, which are not naturally present in the body, are associated with toxicity and significant reductions in metabolic activity at concentrations that enhance tendon mechanical properties. In contrast, we propose that an effective method to restore tendon mechanical properties would be to promote lysyl oxidase (LOX)-mediated collagen crosslinking in tendon during adult tissue healing or fetal tissue development. LOX is naturally occurring in the body, and we previously demonstrated LOX-mediated collagen crosslinking to be a critical regulator of tendon mechanical properties during new tissue formation. In this study, we examined the effects of recombinant LOX treatment on tendon at different stages of development. We found that recombinant LOX treatment significantly enhanced tensile and nanoscale tendon mechanical properties without affecting cell viability or collagen content, density, and maturity. Interestingly, both tendon elastic modulus and LOX-mediated collagen crosslink density plateaued at higher recombinant LOX concentrations, which may have been due to limited availability of adjacent lysine residues that are near enough to be crosslinked together. The plateau in crosslink density at higher concentrations of recombinant LOX treatments may have implications for preventing over-stiffening of tendon, though this requires further investigation. These findings demonstrate the exciting potential for a LOX-based therapeutic to enhance tendon mechanical properties via a naturally occurring crosslinking mechanism, which could have tremendous implications for an estimated 32 million acute and chronic tendon and ligament injuries each year in the U.S.https://www.frontiersin.org/articles/10.3389/fbioe.2022.945639/fulltendoncollagen crosslinkinglysyl oxidasetendon healingmechanical propertiesbirth deformity |
| spellingShingle | Phong K. Nguyen Phong K. Nguyen Aniket Jana Chi Huang Alison Grafton Iverson Holt Michael Giacomelli Catherine K. Kuo Catherine K. Kuo Catherine K. Kuo Catherine K. Kuo Catherine K. Kuo Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment Frontiers in Bioengineering and Biotechnology tendon collagen crosslinking lysyl oxidase tendon healing mechanical properties birth deformity |
| title | Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment |
| title_full | Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment |
| title_fullStr | Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment |
| title_full_unstemmed | Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment |
| title_short | Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment |
| title_sort | tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment |
| topic | tendon collagen crosslinking lysyl oxidase tendon healing mechanical properties birth deformity |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.945639/full |
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