Joseph M. Lane

Joint resurfacing in the rabbit using an autologous osteochondral graft.

In rabbits, joint resurfacing with autologous osteoarticular condylar grafts composed of the articular cartilage and subchondral bone (two to eight millimeters thick) from the lateral femoral condyles was investigated. By means of morphological, histochemical, autoradiographic, and biochemical studies, the grafts were compared with sham and normal controls. When adequately fixed, the grafts remained viable and functionally and structurally intact during the twelve months of the experiment. The subchondral bone underwent rapid replacement in less than six weeks without loss of its supportive function. Resurfacing of a joint using an osteochondral graft is feasible in rabbits.

Effect of the proline analogue azetidine-2-carboxylic acid on collagen synthesis in vivo I. Arrest of collagen accumulation in growing chick embryos☆

Abstract Previous studies demonstrated that the proline analogue azetidine-2-carboxylic acid was incorporated in collagen synthesized in vitro and that the collagen containing the analogue was extruded from cells at a decreased rate. In the present study azetidine-2-carboxylic acid was administered for a 5-day period to rapidly growing chick embryos and it was found that the analogue arrested the accumulation of collagen in the embryos. The effect on collagen accumulation was always more marked than any effect on weight or non-collagen proteins and there was no histological evidence of non-specific toxicity. The decrease in collagen content was accompanied by a marked increase in the fragility of the embryos. Although an increase in the rate of collagen degradation was not completely excluded, the results suggested that the decrease in collagen content of the embryos can be explained by the intracellular synthesis of a collagen which contains the analogue and which cannot be extruded at a normal rate. After the cells have accumulated a large pool of analogue-containing collagen, they reach a new steady state in which both the rate of collagen synthesis and extrusion are decreased.

Inhibitors of Collagen Biosynthesis as a Means of Controlling Scar Formation in Tendon Injury

After tendon injury, the formation of peritendinous adhesions restricts the gliding of the healed tendon. In this study, attempts have been made to reduce the amount of adhesions with four drugs. Four agents which are known to alter collagen biosynthesis were tested for their ability to inhibit scar formation in the repair of an incision in a tendon. α, α-dipyridyl, beta-aminopropionitrile, D-penicillamine and cis-hydroxyproline were all found to decrease the amount of scan formed around the flexor tendon. α, ά-dipyridyl showed significant toxic side effects. Rats treated with beta-am inopropionitnile showed moderate toxicity. D-penicillamine-treated rats showed minimum toxicity, but with the dose employed, this drug was slightly less effective than the others. Cis-hydroxyproline showed no toxic side effects in our experiments. The inhibition of collagen biosynthesis by proline analogues is a new approach to the problem of reducing scar formation. Further study is needed before considering its use in clinical situations.

Regeneration after nerve transection: Effect of inhibition of collagen synthesis

Abstract Dense collagen scar forms at the cut ends of transected nerves, and impedes nerve regeneration. To minimize scarring, we treated rats with the proline analog, cis -hydroxyproline, from day 4 to 21 after sciatic nerve transection and reanastomosis. Twenty-eight days after surgery, there was 47% less collagen in the distal nerve stump of treated rats than of controls. Seventy days after surgery, posterior tibial nerve content of the myelin lipids, sulfatide, and unesterified cholesterol, was 40% higher in treated rats than in controls.

Effect of the proline analogue azetidine-2-carboxylic acid on collagen synthesis in vivo. II. Morphological and physical properties of collagen containing the analogue.

Abstract Chick embryos were treated from day 8 to day 12 with 500 μg per day of azetidine-2-carboxylic acid. Electron microscopy indicated there were essentially no cross-striated collagen fibrils in tendon or skin of the treated embryos. Amino acid analysis of the tendons suggested that the decrease in cross-striated fibrils was accounted for by the decreased collagen content of the tissue. Acid-soluble collagen isolated from the treated embryos had essentially the same amino acid composition as normal collagen except that it contained about 4 residues of azetidine-2-carboxylic acid per 1000 residues of amino acid. The only demonstrable abnormality in the physical properties of the acid-soluble collagen from treated embryos was that the T m value for the helix-coil transition was 1.8° lower and the early part of the melting curve was less sharp than the melting curve of the control. The results did not help to resolve the question of whether collagen-containing azetidine-2-carboxylic acid is extruded from cells at a decreased rate because of the presence of the analogue or because of other changes in the molecule. The observations emphasized, however, that incorporation of proline analogues into collagen produces relatively minor changes in the structure of the molecule but that these minor changes have marked effects on the overall rate at which collagen fibrils are deposited in the extracellular matrix.