Experimental study on the transplantation of articular cartilage
Of great interest in modern medicine is the subject of transplantation in the living body, concerned fundamentally with a shift from any damaged tissue or organ to a new one which will continue to live and function in a healthy manner.
Much work and constant effort is in progress in this field and many accounts have been reported concerning attempts to solve this problem.
Bone grafting, for example, has been highly successful, and now is widely used in orthopedic procedures, with good results.
However, the transplantation of articular cartilage has not yeat been improved to the point to warrant full-scale clinical application, although reports have appeared occasionally since the partial success achieved in man by Lexer(1908) and in animals by Judet(1908), and concerted efforts are at present being made to discover a successful technique.
Medawar(1948) reported that the failure of tissue homografts to "take" is known to be attributable to the active immune response called forth in the host by incompatibility antigens present in the cells of the grafted tissue.
Bacsich and Wyburn(1947) concluded that the special behavior of these grafts is usually ascribed to the avascular nature of cartilage, the cells of which are separated from those of the host by a matrix which acts as a physical barrier and which may, in addition, have a specific protective capacity.
Many investigations have demonstrated that the transplanted cartilage, either autogenous or homogenous, remains viable and persists grossly unaltered for considerable periods. These investigations have also demonstrated that the chondrocytes are alive as evidenced by their ability to metabolized radioactive
sulphur, shown through autoradiography and correlated to the viability of the cells histologically.
Pap and Krompecher(1961) emphasized that the thickness of the graft appeared to be a significant factor in determining the ultimate fate of the graft and that unless the implant is subjected to the stimuli of normal physiological function it
will not survive.
DePalma et al.(1962) and Campbell et al.(1963) disclosed that there was a difference in the incidence of survival or articular cartilage between fresh and delayed grafts.
Peer(1939) and Siffert(1955) observed that study of delayed transplants with preserved cartilage revealed that the cartilage was invaded readily by host fibroblasts and was absorbed. They explained this phenomenon, in which the chondrocytes were killed and the matrix altered, by the manner and agents used to preserve the cartilage.
In addition, DePalma et al.(1963) reported a shorter period of storage appeared to have a beneficial effect on the persistence of the graft in delayed transplants preserved where adequate nutrition was present.
A method of storing cartilage in the living state will be required to solve the problem of delayed grafting.
Low-temperature storage may offer the solution to the banking problem of articular cartilage. this method has been used clinically as a simple reliable technique for storing bone and cornea for future use.
Meanwhile little investigation has yet appeared on transplantation of frozen cartilage.
Simmons and Chrisman(1965) demonstrated for the first time that salicylate has a definite protective effect against degeneration of cartilage, and offered the biochemical explanation that salicylate might significantly inhibit the action of the catabolic enzymes, cathepsins.
In the meantime, uniform success of the transplantation for articular cartilage has remained elusive, and criteria for establishing its success limited.
Thus, accurate appraisal of the ultimate survival of cartilage transplants and factors influencing the fate of the transplants are urgently required for reconstruction of damaged joint surfaces.
This experimental project was designed to evaluate the transplants of articular cartilage which were made especially with reference to functional stimuli, methods of preservation for delayed grafts, and preventive measures against degenerative changes.
The purpose of the study was to investigate the fate of the transplantation of articular cartilage, to clarify the factors influencing success of failure, and to contribute some improvement and progress toward clinical application.
Fifty-three healthy adult mongrel dogs were used for transplantation.
The animals were divided into four large groups with autogenous, fresh homogenous, plasma-stored homogenous and frozen homogenous transplants, and additional supplemental groups were subdivided as salicylate-treated in the plasma-stored and frozen homogenous transplants respectively.
Grafts of articular cartilage with adjoining cancellous bone were transplanted to the knee and muscle.
The grafts, consisting of the articular cartilage and a narrow margin of cancellous bone, measured less than five millimeters in thickness.
Grafts were attempted with transplants of partial fragments from the femora in the region of the femoro-patellar joint.
The fragment was adjusted into a prepared bed in an articular defect of appropriate size and shape, and fixed in position of function. Another fragment was also transplanted into the muscle in each dog.
The dogs were sacrificed weekly for the first four weeks and then approximately at monthly intervals during the duration of the experiment.
The fate of the grafts were investigated in accordance with studies of histology, autoradiography using radioactive sulphul, S**35 and electron microscopy by replica of cartilage surface, at intervals ranging from seven to 365 days.
The results of the experiment are as follows:
1. The transplant in the position of function was accepted functionally and biologically by the host.
2. The osseous portion of the graft served as a template on which appositional new bone was formed, and remodelled along the lines dictated by functional stimuli.
3. The healing process of the margin of the grafted cartilage was filled by ingrowth of granulation tissue derived from the subchondral bone of the host, and this was subsequently transformed into fibrocartilage.
4. The cartilage portion of the autogenous transplants survived and the chondrocytes demonstrated normal ability to metabolize radioactive sulphur, S**35
5. The cartilage of the fresh homogenous transplants also survived and showed excellent concentration of isotope both in the cells and in the matrix. However, old specimens exhibited a small area of mild degeneration, especially of the superficial layer.
6. In the delayed homogenous grafts, the articular cartilage survived initially and shoed varying degrees of delayed degeneration of the cartilage. These changes were much more frequent and more pronounced in the frozen than in the plasma-stored transplants.
7. The salicylate treatment of cartilage did significantly inhibit the development of many of the degenerative changes seen in the untreated cartilage.
8. The synovia showed non-specific inflammatory changes correlated with the degeneration of the cartilage.
9. Heterotopic transplants into muscle, where functional stimuli were not imposed, showed marked degenerative changes, eventually were absorbed, and then were replaced by fibrous tissue. These changes progressed rapidly in the osseous portion and slowly in the cartilage.