Mechanical properties and structure-function relationships in articular cartilage repaired using IGF-I gene-enhanced chondrocytes.
Abstract: Several studies have demonstrated the benefits of IGF-I gene therapy in enhancing the histologic and biochemical content of cartilage repaired by chondrocyte transplantation. However, there is little to no data on the mechanical performance of IGF-I augmented cartilage grafts. This study evaluated the compressive properties of full-thickness chondral defects in the equine femur repaired with and without IGF-I gene therapy. Animals were randomly assigned to one of three study cohorts based on chondrocyte treatment provided in each defect: (i) IGF-I gene delivered by recombinant adeno-associated virus (rAAV)-5; (ii) AAV-5 delivering GFP as a reporter; (iii) naïve cells without virus. In each case, the opposite limb was implanted with a fibrin carrier without cells. Samples were prepared for confined compression testing to measure the aggregate modulus and hydraulic permeability. All treatment groups, regardless of cell content or transduction, had mechanical properties inferior to native cartilage. Overexpression of IGF-I increased modulus and lowered permeability relative to other treatments. Investigation of structure-property relationships revealed that Ha and k were linearly correlated with GAG content but logarithmically correlated with collagen content. This provides evidence that IGF-I gene therapy can improve healing of articular cartilage and can greatly increase the mechanical properties of repaired grafts.
© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Publication Date: 2015-09-08 PubMed ID: 26308948DOI: 10.1002/jor.23038Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research paper explores the impact of using IGF-I gene therapy in improving the mechanical properties of repaired cartilage grafts.
Introduction
- The study is focused on the use of IGF-I gene therapy to enhance the mechanical performance and healing process of articular cartilage grafts. Prior research into this topic demonstrated benefits in terms of histological and biochemical content, but the mechanical performance of the treated grafts remained unexplored.
- The authors sought to fill this gap in knowledge by conducting experiments with equine femur models. The objective was to evaluate compressive properties of full-thickness chondral defects repaired with and without IGF-I gene therapy.
Method
- The study involved the use of three cohorts of animals. In these groups, chondrocyte treatment varied: one involved IGF-I gene delivery using a recombinant adeno-associated virus (rAAV)-5, the second had an AAV-5 delivering GFP (Green Fluorescent Protein) as a marker, and the third group consisted of naïve (unmodified) cells.
- The comparison limb in each case was implanted with a fibrin carrier devoid of cells. Once prepared, the samples were subjected to confined compression testing to measure attributes like aggregate modulus (a measure of a material’s resistance to uniform compression) and hydraulic permeability.
Results
- The authors found that all treatment groups, irrespective of cell content or the process of transduction (genetic modification using a virus), exhibited mechanical properties that were inferior when compared to native cartilage.
- However, it was evident that the overexpression of IGF-I led to an increased modulus and decreased permeability as compared to other treatments. The results indicate enhancement of the graft’s mechanical properties following IGF-I gene therapy.
Conclusion
- The study successfully established that IGF-I gene therapy can enhance the healing of articular cartilage, noticeably boosting the mechanical characteristics of repaired grafts.
- Understanding the structure-property relationships pertinent to this study, such as the linear connection between Ha (aggregate modulus) and k (hydraulic permeability), and GAG content and the logarithmic correlation with collagen content, provides further insight into the contribution of IGF-I gene therapy towards cartilage repair.
Cite This Article
APA
Griffin DJ, Ortved KF, Nixon AJ, Bonassar LJ.
(2015).
Mechanical properties and structure-function relationships in articular cartilage repaired using IGF-I gene-enhanced chondrocytes.
J Orthop Res, 34(1), 149-153.
https://doi.org/10.1002/jor.23038 Publication
Researcher Affiliations
- Department of Biomedical Engineering, Cornell University, Ithaca, New York.
- College of Veterinary Medicine, Cornell University, Ithaca, New York.
- College of Veterinary Medicine, Cornell University, Ithaca, New York.
- Department of Biomedical Engineering, Cornell University, Ithaca, New York.
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York.
MeSH Terms
- Animals
- Cartilage, Articular / physiology
- Cartilage, Articular / surgery
- Compressive Strength
- Genetic Therapy
- Horses
- Immunohistochemistry
- Insulin-Like Growth Factor I / genetics
- Random Allocation
Grant Funding
- 5R01-AR055373 / NIAMS NIH HHS
Citations
This article has been cited 12 times.- Watson-Levings RS, Palmer GD, Levings PP, Dacanay EA, Evans CH, Ghivizzani SC. Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation.. Front Bioeng Biotechnol 2022;10:901317.
- Trompeter N, Gardinier JD, DeBarros V, Boggs M, Gangadharan V, Cain WJ, Hurd L, Duncan RL. Insulin-like growth factor-1 regulates the mechanosensitivity of chondrocytes by modulating TRPV4.. Cell Calcium 2021 Nov;99:102467.
- Saghati S, Nasrabadi HT, Khoshfetrat AB, Moharamzadeh K, Hassani A, Mohammadi SM, Rahbarghazi R, Fathi Karkan S. Tissue Engineering Strategies to Increase Osteochondral Regeneration of Stem Cells; a Close Look at Different Modalities.. Stem Cell Rev Rep 2021 Aug;17(4):1294-1311.
- Orth P, Eldracher M, Cucchiarini M, Madry H. Small-Diameter Subchondral Drilling Improves DNA and Proteoglycan Content of the Cartilaginous Repair Tissue in a Large Animal Model of a Full-Thickness Chondral Defect.. J Clin Med 2020 Jun 18;9(6).
- Yang F, Zhang Y, Liu B, Cao M, Yang J, Tian F, Yang P, Qin K, Zhao D. Basic fibroblast growth factor and agarose gel promote the ability of immune privilege of allogeneic cartilage transplantation in rats.. J Orthop Translat 2020 May;22:73-80.
- Yan X, Chen YR, Song YF, Yang M, Ye J, Zhou G, Yu JK. Scaffold-Based Gene Therapeutics for Osteochondral Tissue Engineering.. Front Pharmacol 2019;10:1534.
- Md Nazir N, Zulkifly AH, Khalid KA, Zainol I, Zamli Z, Sha'ban M. Matrix Production in Chondrocytes Transfected with Sex Determining Region Y-Box 9 and Telomerase Reverse Transcriptase Genes: An In Vitro Evaluation from Monolayer Culture to Three-Dimensional Culture.. Tissue Eng Regen Med 2019 Jun;16(3):285-299.
- Davies RL, Kuiper NJ. Regenerative Medicine: A Review of the Evolution of Autologous Chondrocyte Implantation (ACI) Therapy.. Bioengineering (Basel) 2019 Mar 13;6(1).
- Cucchiarini M, Madry H. Biomaterial-guided delivery of gene vectors for targeted articular cartilage repair.. Nat Rev Rheumatol 2019 Jan;15(1):18-29.
- Bonnevie ED, Mauck RL. Physiology and Engineering of the Graded Interfaces of Musculoskeletal Junctions.. Annu Rev Biomed Eng 2018 Jun 4;20:403-429.
- Bellavia D, Veronesi F, Carina V, Costa V, Raimondi L, De Luca A, Alessandro R, Fini M, Giavaresi G. Gene therapy for chondral and osteochondral regeneration: is the future now?. Cell Mol Life Sci 2018 Feb;75(4):649-667.
- Frisch J, Orth P, Rey-Rico A, Venkatesan JK, Schmitt G, Madry H, Kohn D, Cucchiarini M. Peripheral blood aspirates overexpressing IGF-I via rAAV gene transfer undergo enhanced chondrogenic differentiation processes.. J Cell Mol Med 2017 Nov;21(11):2748-2758.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
