Microfracture Augmentation With Trypsin Pretreatment and Growth Factor-Functionalized Self-assembling Peptide Hydrogel Scaffold in an Equine Model.
Abstract: Microfracture augmentation can be a cost-effective single-step alternative to current cartilage repair techniques. Trypsin pretreatment combined with a growth factor-functionalized self-assembling KLD hydrogel ("functionalized hydrogel") has been shown to improve overall cartilage repair and integration to surrounding tissue in small animal models of osteochondral defects. Microfracture combined with trypsin treatment and a functionalized hydrogel will improve reparative tissue quality and integration as compared with microfracture alone in an equine model. Controlled laboratory study. Bilateral cartilage defects (15-mm diameter) were created on the medial trochlear ridge of the femoropatellar joints in 8 adult horses (16 defects total). One defect was randomly selected to receive the treatment, and the contralateral defect served as the control (microfracture only). Treatment consisted of 2-minute trypsin pretreatment of the surrounding cartilage, subchondral bone microfracture, and functionalized hydrogel premixed with growth factors (platelet-derived growth factor and heparin-binding insulin-like growth factor 1). After surgery, all horses were subjected to standardized controlled exercise on a high-speed treadmill. Clinical evaluation was conducted monthly, and radiographic examinations were performed at 2, 16, 24, 32, 40, and 52 weeks after defect creation. After 12 months, all animals were euthanized. Magnetic resonance imaging, arthroscopy, gross pathologic evaluation of the joint, histology, immunohistochemistry, and biomechanical analyses were performed. Generalized linear mixed models (with horse as random effect) were utilized to assess outcome parameters. When values were <.05, pairwise comparisons were made using least squares means. Improved functional outcome parameters were observed for the treatment group, even though mildly increased joint effusion and subchondral bone sclerosis were noted on imaging. Microscopically, treatment resulted in improvement of several histologic parameters and overall quality of repaired tissue. Proteoglycan content based on safranin O-fast green staining was also significantly higher in the treated defects. Trypsin treatment combined with functionalized hydrogel resulted in improved microfracture augmentation. Therapeutic strategies for microfracture augmentation, such as those presented in this study, can be cost-effective ways to improve cartilage healing outcomes, especially in more active patients.
Publication Date: 2021-06-23 PubMed ID: 34161182DOI: 10.1177/03635465211021798Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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The research carries out an investigation on the effectiveness of a method to repair damaged cartilage in horses utilizing a combined approach of microfracture, trypsin pre-treatment, and application of a growth factor-filled self-assembling hydrogel. The study shows improved repair, particularly in the quality of repaired tissue, over traditional microfracture repair.
Research Methodology
- The study created matching cartilage defects in 8 adult horses, with one defect receiving the combined treatment and the other serving as a control which only underwent microfracture.
- The procedure used for this innovative treatment included pre-treating the surrounding cartilage for 2 minutes with trypsin, executing subchondral bone microfracture, and use of functionalized hydrogel laced with platelet-derived growth factor and heparin-binding insulin-like growth factor 1.
- The horses were made to perform controlled exercise on a high-speed treadmill after surgery. Clinical examinations took place each month, with radiographic tests at various intervals after the initial procedure.
- Post one year, horses were euthanized for the analysis of the repair which included MRI, arthroscopy, evaluation of the joint, histology, immunohistochemistry, and biomechanical analyses.
Research Findings
- The group that received the experimental treatment demonstrated improved functional outcomes, despite marginally increased joint effusion and subchondral bone sclerosis as identified in imaging studies.
- Microscopic analysis revealed that the combined protocol led to better histologic factors and overall quality of repaired tissue.
- The amount of proteoglycans, determined by safranin O-fast green staining, was significantly higher in the treated defects. These results signify an improved cartilage repair as proteoglycans lend resilience to the cartilage and are essential for its function.
Implications of the Study
- The combination of trypsin treatment and functionalized hydrogel drastically improved microfracture augmentation, providing a potentially effective surgical therapy for improved cartilage repair.
- This experiment’s successful results are not only applicable to horses but also imply the potential for similar treatment methods to be adopted in other animals, including humans, to repair cartilage damage. This is especially vital for active patients, where optimized cartilage healing is required to ensure active lifestyles can be maintained.
- By improving the outcome of a basic procedure like microfracture, the integrated methodology could offer a cost-effective solution to current cartilage repair techniques.
Cite This Article
APA
Zanotto GM, Liesbeny P, Barrett M, Zlotnick H, Frank E, Grodzinsky AJ, Frisbie DD.
(2021).
Microfracture Augmentation With Trypsin Pretreatment and Growth Factor-Functionalized Self-assembling Peptide Hydrogel Scaffold in an Equine Model.
Am J Sports Med, 49(9), 2498-2508.
https://doi.org/10.1177/03635465211021798 Publication
Researcher Affiliations
- Department of Clinical Sciences, Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Station, Texas, USA.
- Departments of Biological, Electrical, and Mechanical Engineering, Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
- Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Science, Colorado State University, Fort Collins, Colorado, USA.
- Departments of Biological, Electrical, and Mechanical Engineering, Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
- Departments of Biological, Electrical, and Mechanical Engineering, Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
- Departments of Biological, Electrical, and Mechanical Engineering, Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
- Department of Clinical Sciences, Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
MeSH Terms
- Animals
- Cartilage, Articular / surgery
- Fractures, Stress
- Horses
- Humans
- Hydrogels / pharmacology
- Peptides
- Platelet-Derived Growth Factor
- Trypsin
Citations
This article has been cited 10 times.- Binaymotlagh R, Chronopoulou L, Palocci C. Peptide-Based Hydrogels: Template Materials for Tissue Engineering. J Funct Biomater 2023 Apr 19;14(4).
- Bakhtiary N, Ghalandari B, Ghorbani F, Varma SN, Liu C. Advances in Peptide-Based Hydrogel for Tissue Engineering. Polymers (Basel) 2023 Feb 21;15(5).
- Ma C, Li H, Lu S, Li X, Wang S, Wang W. Tryptase and Exogenous Trypsin: Mechanisms and Ophthalmic Applications. J Inflamm Res 2023;16:927-939.
- Wang Y, Chen Y, Wei Y. Osteoarthritis animal models for biomaterial-assisted osteochondral regeneration. Biomater Transl 2022;3(4):264-279.
- DePhillipo NN, Hendesi H, Aman ZS, Lind DRG, Smith J, Dodge GR. Preclinical Use of FGF-18 Augmentation for Improving Cartilage Healing Following Surgical Repair: A Systematic Review. Cartilage 2023 Mar;14(1):59-66.
- Binaymotlagh R, Chronopoulou L, Haghighi FH, Fratoddi I, Palocci C. Peptide-Based Hydrogels: New Materials for Biosensing and Biomedical Applications. Materials (Basel) 2022 Aug 25;15(17).
- Seabaugh KA, Barrett MF, Rao S, McIlwraith CW, Frisbie DD. Examining the Effects of the Oral Supplement Biota orientalis in the Osteochondral Fragment-Exercise Model of Osteoarthritis in the Horse. Front Vet Sci 2022;9:858391.
- Zlotnick HM, Locke RC, Hemdev S, Stoeckl BD, Gupta S, Peredo AP, Steinberg DR, Carey JL, Lee D, Dodge GR, Mauck RL. Gravity-based patterning of osteogenic factors to preserve bone structure after osteochondral injury in a large animal model. Biofabrication 2022 Jul 5;14(4).
- Aswathy SH, Narendrakumar U, Manjubala I. An Overview of Approaches and Evaluation Methods for Tissue-Engineered Articular Cartilage Constructs in Animal Models. Ann Biomed Eng 2025 Nov;53(11):3009-3030.
- Massengale M, Massengale JL, Benson CR, Baryawno N, Oki T, Steinhauser ML, Wang A, Balani D, Oh LS, Randolph MA, Gill TJ 3rd, Kronenberg HM, Scadden DT. Adult Prg4+ progenitors repair long-term articular cartilage wounds in vivo. JCI Insight 2023 Sep 8;8(17).
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