Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects.
Abstract: Cartilage resurfacing by chondrocyte implantation, with fibrin used as a vehicle, was examined in large (12 mm) full-thickness articular cartilage defects in horses. Articular chondrocytes, isolated from a 9-day-old foal, were mixed with fibrinogen and injected with thrombin, in a 1:1 mixture, into 12 mm circular defects on the lateral trochlea of the distal femur of eight normal horses. The contralateral femoropatellar (knee) joint served as a control in which the defect was left empty. Synovial fluid from the femoropatellar joints was sampled on days 0, 4, 7, 30, 120, and 240 postoperatively. Groups of four horses were killed at 4 or 8 months postoperatively, and the repair tissue was evaluated by gross and histologic examination with use of hematoxylin and eosin and safranin O staining and by autoradiography. Biochemical analyses included quantitation of proteoglycan, total collagen, and type-II collagen in the repair tissue. Grossly, grafted defects had improved filling of the cartilage lesions; histologically, these areas consisted of differentiated chondrocytes in the deep and middle zones. The cellular arrangement in these zones resembled that of hyaline cartilage. The control defects contained poorly attached fibrous tissue throughout. Grafted tissue at 8 months had increased proteoglycan synthesis evident by both safranin O staining and autoradiography. Glycosaminoglycan quantitation by dye-binding assay confirmed a significantly elevated glycosaminoglycan content in grafted defects (58.8 micrograms/mg of dry weight) compared with control defects (27.4 micrograms/mg; p < 0.05). Similarly, the levels of chondroitin sulfate/dermatan sulfate was significantly elevated in the grafted defects, and this was the predominant glycosaminoglycan epitope present. There was a statistically significant (p < 0.05) increase in type-II collagen in the grafted tissue at 8 months (61.2% grafted; 25.1% control). This resurfacing attempt with use of allograft chondrocytes, secured in large full-thickness articular defects with polymerized fibrin, resulted in an improved cartilage surface in comparison with the control defects, a significantly greater aggrecan level, and a significantly higher proportion of type-II collagen.
Publication Date: 1994-07-01 PubMed ID: 8064479DOI: 10.1002/jor.1100120405Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research paper studies the application of a mixture of chondrocytes and fibrin, for the purpose of repairing large cartilage damages in horses. The paper shows the effectiveness of this approach, leading to improved tissue regeneration, compared to control groups.
Methodology
- The experiment involved large (12 mm) full-thickness articular cartilage defects in horses. A group of healthy horses were subjected to this procedure.
- Articular chondrocytes were taken from a 9-day-old foal and were mixed with fibrinogen and thrombin in equal proportions.
- This mixture was injected into the aforementioned cartilage defects in the horses, while the corresponding space on the other knee joint was left empty to serve as a control.
- Synovial fluid from the knee joints of the test subjects was analyzed at several postoperative stages (on days 0, 4, 7, 30, 120, and 240).
- The experimental horses were dissected at either 4 or 8 months post-operation.
- The repaired tissues were studied through numerous methods, including histological analysis, biochemical analysis and autoradiography.
Findings
- The injected defects showed improved filling of the damaged cartilage.
- Under a histological examination, the repaired sites exhibited distinct chondrocytes in the deep and middle zones of the cartilage.
- The cell arrangement in these zones resembled that of hyaline cartilage.
- On the contrary, the control group displayed poorly attached fibrous tissue throughout the damaged site.
- The tissue in the injected area showed increased proteoglycan production at the 8-month mark.
- Quantitative dye-binding assay revealed a significantly elevated presence of glycosaminoglycan in the repaired sites. Similarly, the levels of chondroitin sulfate/dermatan sulfate, which constitute a prominent subset of glycosaminoglycan, were also significantly higher in the repaired sites compared to the control sites.
- A significant increase in type-II collagen was also detected in the repaired tissue after 8 months.
Conclusion
The researchers conclude that resurfacing cartilage damages using allograft chondrocytes in conjunction with polymerized fibrin provides promising results. This method resulted in significantly improved cartilage surface repair, higher aggrecan levels, and a markedly elevated proportion of type-II collagen, thereby superseding the regeneration performance of untreated control defects.
Cite This Article
APA
Hendrickson DA, Nixon AJ, Grande DA, Todhunter RJ, Minor RM, Erb H, Lust G.
(1994).
Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects.
J Orthop Res, 12(4), 485-497.
https://doi.org/10.1002/jor.1100120405 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
MeSH Terms
- Animals
- Autoradiography
- Bone Matrix / chemistry
- Bone Matrix / metabolism
- Bone Matrix / transplantation
- Cartilage Diseases / surgery
- Cartilage, Articular / chemistry
- Cartilage, Articular / cytology
- Cartilage, Articular / transplantation
- Cell Separation
- Cell Transplantation
- Chondroitin Sulfates / analysis
- Chondroitin Sulfates / metabolism
- Collagen / analysis
- Collagen / metabolism
- Female
- Fibrin / analysis
- Fibrin / metabolism
- Horses
- Knee Joint
- Male
- Transplantation, Homologous
Grant Funding
- AR 20793 / NIAMS NIH HHS
- AR 35664 / NIAMS NIH HHS
Citations
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