Collagen Fibril Diameters in the Rabbit Medial Collateral Ligament Scar

Abstract

Previous transmission electron microscopic investigations of collagen fibril diameters in rabbit medial collateral ligament (MCL) scars have indicated a homogeneous population of small fibrils for the first 40 weeks of healing. In this study, four 8 mm MCL gap scars were studied at 78 weeks of healing and another three at 104 weeks. Results showed increased heterogeneity in the distribution of fibril diameters in all scars, with the appearance of progressively slightly larger fibrils in 78 and 104 week specimens. All longer term scars still contained roughly 90% small fibrils plus some "patches" of larger fibrils, but there was considerable variation between animals in these proportions. No scar contained the fibril populations typical of uninjured adult rabbit MCLs. These results suggest slow but on-going collagen fibril turnover and remodeling in this gap healing rabbit MCL model via currently unidentified mechanisms.

Ligament Injury and Healing: A Review of Current Clinical Diagnostics and Therapeutics

“…Some of the identifiable differences between remodeled matrix and normal ligament matrix include alterations to proteoglycans and types of collagen, failure of collagen crosslinks to mature, persistence of small collagen fibril diameters, altered cell connections, increased vascularity, abnormal innervations, increased cellularity and the incomplete resolution of matrix flaws [1,28,49,[50][51][52][53][54]. Although research suggests that persisting collagen abnormalities may be the most critical aspect of regaining ligament tissue function, virtually all other tissue components are likely to play equally important roles in tissue function, either directly or indirectly [46,49,[55][56][57].…”

“…However, after injury, fibroblasts primarily synthesize type III collagen, not type I collagen, which it produces to a much smaller degree [60,61]. The abnormal cross-linking of collagen and the smaller diameters in collagen fibrils in repaired ligament tissue cause weakness in both tissue strength and tissue stiffness, often remaining for months or years after initial injury [46,49,50,52,56,62,63]. In addition, evidence suggests that remodeled collagen fibrils are not packed as densely as in normal ligaments, and the remodeled tissue appears to contain materials other than collagen, such as blood vessels, fat cells, and inflammatory cell pockets, all of which contribute to its weakness [1,46,49].…”

“…More specifically, ACL and MCL structures tend to heal at varying rates comparatively, and the quality of remodeled tissue overall among different animal species remains inferior to that of normal ligaments [53,54,56,60,63,68,[79][80][81][82][83]. In fact, studies of healing ligaments have consistently shown that certain ligaments do not heal independently following rupture, and those that do heal, do so with characteristically inferior compositional properties compared with normal tissue [64,74,84,85].…”

Effects of a therapeutic laser on the ultrastructural morphology of repairing medial collateral ligament in a rat model

“…Since the late 1970s, studies have been done to investigate the ultrastructural morphology of collagen fibrils with electron microscopy and image analysis techniques [14][15][16][17][18][19][20][21][22][23]. Reports on the correlation between biomechanical strength and fibril size of connective tissues are equivocal [14,16,23].…”

Fate of donor bone marrow cells in medial collateral ligament after simulated autologous transplantation

“…Associated with abnormal biomechanical properties, there were increases in the ratio of type III and V collagen over type I collagen and a decrease of hydroxypyrimidinium crosslinks (Kavalkovich et al, 1997). Furthermore, the collagen fibril diameter, when examined under transmission electron microscopy, remained smaller than normal up to 2 years after injury (Frank et al, 1997). As a result, much effort has been made to enhance the properties of the healing ligament.…”