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KMID : 0438219750120030743
Korea University Medical Journal
1975 Volume.12 No. 3 p.743 ~ p.759
An Experimental Study on the Effect of Chymotrypsin upon the Repair of Articular Cartilage of the Patella following Operative Defects in Matured Rabbits


Abstract
Many investigators have tried to determine whether an injured articular cartilage is capable of regeneration or not.
The reparative processes which occur following the injury to the articular cartilage have been a controversial subject among many investigators for a long time. Although some of them reported regenerative process of articular cartilage, yet regarding to the extend of the healing, the nature of the healing tissue and the origin of the derived tissue etc., many things are still left unsolved.
From an orthopedic aspect, the regeneration of damaged cartilage is one of the interesting subjects as regards to the prognosis of injured articular cartiage as well as the fate of the defects of articular cartilage in various arthritides:-pyogenic arthritis, osteoarthritis, rheumatoid arthritis and metabolic disorders.
Recently, intra-articular cortisone injection is frequently used in the treatment of arthritis.
Proteolytic enzymes such as chymopapain and chymotrypsin are now used frequently in the treatment of various arthritides after Smith applied such enzymes for dissolution of the nucleus pulposus in human. However, to the best knowledge of this author, there has been little histological study on the effect of chymotrypsin on the regenerative process of the injured articular cartilage.
The author therefore has undertaken an experimental study in order to observe comparatively the histological changes occuring in the injured articular cartilages of the patella of rabbit following intra-articular injection of chymotrypsin.
Material and method;
One hundred and twenty matured rabbits, weighing 1500-20009m were evenly divided into 3 (A, B, C) groups depending on the depth of the injury created on the patella.
The animals were operated on in sterile conditions under pentothal sodium anesthesia. The depth of the operative defects varied as follows;
Group A: The defect extended to the intermediated or radiate zone of articular cartilage with the calcified zone preserved.
Group B; The defect extened to the calcified zone of the cartilage and the subchondral bone was not exposed.
Group C; The defect was made through the entire layers of the cartilage exposing the subchondral boi:e.
In the chymotrypsin-treated groups, 5mg of chymotrypsin (Mochida) was injected into the articular cavity before closing the knee joint.
The operated animals were sacrificed at intervals of 1, 2, 3, 4, 6, 8, 12, 13, 14 and 15 weeks respectively after the creation of the articular cartilage injury, both patellas were removed and placed in 10% formalin solution and fixed for a day. After fixation they were decalcified and then paraffin blocks were prepared. Multiple sections of each specimen were cut at 51¢¥( and stained with hematoxylin and eosin for histological observation.
The summary of the histological finding is as follows;
a) In control group;
1. It was noticed that the defect in the superficial surface of the cartilage was filled with new hyaline cartilage by cellular proliferation directly from the adjacent margins of the remaining cartilage.
2. In the defects involving the calcified zone of carticular artilage without exposing subchondral bone, the degenerative change near the defect continued until 12th week and proliferation of small vessels were seen in the subchondral bone.
3. When the defect extended deeply to expose subchondral bone, the granulation tissue was at first derived from the subchondral intertrabecular tissue and covered the defect.
The reparative changes passed through a few stages of fibrous tissue and fibrocartilage to the formation of a mature form of hyaline cartilage.
4. In these regenerative processes the following tissues could be observed to appear; fibrin, granulation tissue, connective tissue, cartilage cells in connective tissue, fibrocartilage and new atypical hyaline cartilage.
5. Regeneration of hyaline cartilage was seen in the defects of superficial and the entire layers down to the subchondral bone, the repair of the injured cartilage was more prominent in the latter.
b) In chymotrypsin treated group:
1. It was noticed either meager or similar comparing with the control group of the superficial defect in cartilage zone in the respect of the new hyaline cartilage from cellular proliferation of the adjacent cartilage or directly from the adjacent margins of the remaining cartilage.
2. In the defect of the medium depth articular cartilage down to partial or complete remaining of calcified zone, new regenerative tissue was not seen at all and the degenerative change near the defect was continuously seen up to 12th week.
3. In the deep defect of entire layers group, the reparative process was noticed as same as the control groups but extremely delayed.
4. The regeneration tissues in the defect of the articular cartilage were compared of fibrous tissue, fibrous cartilage and immature hyaline cartilage, and they were decreased in both quantity and quality, and they were also delayed in the repair process comparing with the control group.
5. Chymotrypsin inhibits the regeneration showing the decrease of chondrocytes and the degeneration of cartilage matrix.
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