F. W. Keeley

An autogenous graft of tibial periosteum was sutured (with its cambium layer facing into the joint) to the base of a five by ten-millimeter full-thickness defect in the patellar groove of each of forty-five adolescent rabbits. The rabbits were randomly treated postoperatively by either four weeks of immobilization in a cast, intermittent active motion in a cage, or two weeks of continuous passive motion. One year postoperatively, the regenerated tissue from each rabbit was analyzed macroscopically, histologically, histochemically, and biochemically. Gross degenerative changes were seen in 57 per cent of the rabbits that had been immobilized in a cast, in 73 per cent of the rabbits that had been allowed intermittent active motion, and in 22 per cent of the rabbits that had been subjected to continuous passive motion (p less than 0.05). Out of a possible score of 7.0 points for the nature of the regenerated tissue, the scores for the three groups were: immobilization in a cast, 4.1 points; intermittent active motion, 4.0 points; and continuous passive motion, 5.9 points (p greater than 0.05). Out of a possible perfect combined score of 10.0 points for the structural characteristics of the regenerated tissue, the cast-immobilization group scored 3.8 points; the intermittent active-motion group, 2.5 points; and the continuous passive-motion group, 6.4 points (p less than 0.001). The total scores for freedom from cellular changes of degeneration, a perfect score being 5.0 points, were: immobilization in a cast, 2.4 points; intermittent active motion, 2.3 points; and continuous passive motion, 3.9 points (p less than 0.01). Degenerative changes in the adjacent cartilage, which were noted in 42 and 46 per cent of the knees in the immobilization and intermittent active-motion groups, respectively, were not found in the knees that had been subjected to continuous passive motion (p less than 0.05). The total indices, which were derived by combining the scores for all categories (maximum, 24.0 points), revealed that the index for the continuous passive-motion group was significantly better than the index for either of the other two groups: immobilization in a cast, 12.9 points; intermittent active motion, 11.2 points; and continuous passive motion, 19.2 points (p less than 0.0005).(ABSTRACT TRUNCATED AT 400 WORDS)

A rectangular graft of autogenous tibial periosteum was sutured (with its cambium layer facing into the joint) onto the base of a five by ten-millimeter full-thickness defect in the patellar groove of each of 143 adolescent and adult rabbits. The rabbits were managed postoperatively by either immobilization, intermittent active motion, continuous passive motion for two weeks, or continuous passive motion for four weeks. When the animals were killed four weeks postoperatively, the contour of the patellar groove had been restored in all of the rabbits in the group that had had four weeks of continuous passive motion, and the newly formed tissue in all of the defects in this group had the gross, histological, and histochemical appearance of smooth, intact hyaline articular cartilage. Histologically, the nature of the tissue that had formed, as well as its surface regularity, structural integrity, and bonding to the adjacent cartilage, were significantly better in the group that had had four weeks of continuous passive motion than in any of the other groups. The results were significantly worse when the orientation of the periosteal graft was reversed (that is, when it had been sutured into the defect with the cambium layer of the graft facing the subchondral bone rather than into the joint) or when no periosteal graft was used. Biochemical analyses revealed that, in the group that had had four weeks of continuous passive motion, the total hexosamine content, the levels of chondroitin sulphate and keratan sulphate, and the ratio of galactosamine to glucosamine were all comparable with the values for normal articular cartilage. In contrast, in the groups that were treated by immobilization, intermittent active motion, or two weeks of continuous passive motion, as well as in the adult rabbits, the content of the first three of these substances was significantly less than normal. In the groups that were treated by immobilization, intermittent active motion, or two weeks of continuous passive motion, 32 to 47 per cent of the total collagen was type II, while in the group that had had four weeks of continuous passive motion, 93 per cent of the total collagen was type II. These results demonstrate that, under the influence of continuous passive motion, free autogenous periosteal grafts can repair a large full-thickness defect in a joint surface by producing tissue that resembles articular cartilage grossly, histologically, and biochemically, and that contains predominantly type-II collagen.

Elastin is the major extracellular matrix protein of large arteries such as the aorta, imparting characteristics of extensibility and elastic recoil. Once laid down in tissues, polymeric elastin is not subject to turnover, but is able to sustain its mechanical resilience through thousands of millions of cycles of extension and recoil. Elastin consists of ca. 36 domains with alternating hydrophobic and cross-linking characteristics. It has been suggested that these hydrophobic domains, predominantly containing glycine, proline, leucine and valine, often occurring in tandemly repeated sequences, are responsible for the ability of elastin to align monomeric chains for covalent cross-linking. We have shown that small, recombinantly expressed polypeptides based on sequences of human elastin contain sufficient information to self-organize into fibrillar structures and promote the formation of lysine-derived cross-links. These cross-linked polypeptides can also be fabricated into membrane structures that have solubility and mechanical properties reminiscent of native insoluble elastin. Understanding the basis of the self-organizational ability of elastin-based polypeptides may provide important clues for the general design of self-assembling biomaterials.

SALTER, ROBERT B. M.D.; BELL, ROBERT S. M.D.; KEELEY, FREDERICK W. Ph.D.Editor(s): ALBRIGHT, JAMES A. M.D.; MILLAR, EDWARD A. M.D. Author Information

Changes in elastin and collagen synthesis in the pulmonary artery wall, assessed both biochemically and ultrastructurally, were related to the development of progressive pulmonary hypertension induced by the toxin monocrotaline. Male Sprague-Dawley rats (200 to 225 gm) were injected subcutaneously in the hind flank with either monocrotaline (60 mg/kg) or an equivalent volume of saline and studied 8, 16 and 28 days later. At each time point, the right ventricle and left ventricle with septum were separated and weighed to follow the development of right ventricular hypertrophy. The hilar pulmonary artery was assessed by light microscopy for medial hypertrophy and by electron microscopy for changes in the endothelium, subendothelium and media. The mainstem pulmonary artery was used to determine synthesis of elastin and collagen by in vitro incorporation of [14C]proline into nonelastin, [14C]hydroxyproline into collagen, and [3H]valine into cyanogen bromide-insoluble elastin. In addition, total content of insoluble elastin was determined by weight of the residue after cyanogen bromide digestion and of collagen by total hydroxyproline content in sodium dodecyl sulfate and cyanogen bromide extracts. Eight days after monocrotaline injection, there was pulmonary artery endothelial swelling and a significant decrease in the number of myoendothelial junctions (p less than 0.05) associated with a decreased proportion of amorphous elastin in the media (p less than 0.01). Sixteen days after monocrotaline injection, a decrease in the proportion of elastin in the media was still evident (p less than 0.01) despite an apparent increase in insoluble elastin synthesis. Moreover, the amorphous elastin was distributed preferentially in small islands rather than in laminae (p less than 0.05). Twenty-eight days after monocrotaline injection, medial and right ventricular hypertrophy had developed (p less than 0.05 and p less than 0.01, respectively). At the same time, there was a striking increase in both insoluble elastin synthesis and total insoluble elastin content (p less than 0.01 for both) and an increase in collagen synthesis and total collagen content (p less than 0.05 for both). In addition, the ratio of insoluble elastin synthesis to collagen synthesis was greater than in controls (p less than 0.01), whereas the ratio of total insoluble elastin to total collagen did not change. On ultrastructural analysis, the proportion of amorphous elastin in the vessel wall relative to other elements remained low (p less than 0.01) and was distributed throughout the media as increased numbers of small islands (p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)