Rabbit medial collateral ligament scar weakness is associated with decreased collagen pyridinoline crosslink density

Abstract

This study was carried out to quantify the potential associations between material strength and both collagen concentration and pyridinoline collagen crosslink density in the healing medial collateral ligament of the rabbit and to compare these parameters with those of normal ligaments. The right hindlimbs of 24 skeletally mature (12-month-old) New Zealand White rabbits were subjected to a standardized 4 mm midsubstance "gap" injury to the medial collateral ligament. The animals were killed in groups of six at postoperative intervals of 3, 6, 14, or 40 weeks, and the femur-medial collateral ligament-tibia complexes were mechanically tested in tension to failure. Subsequent to mechanical testing, the failure sites of the ligaments were assessed for concentrations of hydroxyproline and hydroxylysyl pyridinoline. Nine additional rabbits served as age-matched normal controls. In healing ligaments, normal collagen concentrations were reached in less than 14 weeks, but the hydroxylysyl pyridinoline crosslink densities remained low and were only 45% of the control values after 40 weeks of healing. Similarly, mechanical values remained much less than the controls. Linear regression analysis of data on scar tissue alone showed a moderately strong positive correlation between hydroxyproline concentration and material strength (r2 = 0.51, p = 0.0001) but no correlation between crosslink density and strength of scar tissue. A similar pattern of correlation was obtained between the elastic modulus of the scar tissue and the biochemical variables, but the r2 values were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…Since remodeled ligament tissue is morphologically and biomechanically inferior to normal ligament tissue, ligament laxity results, causing functional disability of the affected joint and predisposing other soft tissues in and around the joint to further damage. 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].…”

Strength of medial structures of the knee joint are decreased by isolated injury to the medial collateral ligament and subsequent joint immobilization

“…Studies of the rat medial collateral ligament (MCL) used healing times on the order of 2 weeks typically, but some were as short as 1 week [2,4,7,13,14,16,22]. Studies of the rabbit MCL covered a large range of healing times from 3 to 104 weeks (2 years) [3,5,6,[8][9][10][11]. Likewise, studies of the canine MCL spanned 6 to 48 weeks (1 year) [12,15,21].…”

Effects of basic fibroblast growth factor (bFGF) on early stages of tendon healing: A rat patellar tendon model

“…The restoration of me-chanical strength is the goal of tendon healing. The ultimate stress and pyridinoline content are parameters closely associated with mechanical strength (Frank et al 1995, Woo et al 1997. In the present study, 1 and 2 weeks after the injury were selected for measuring these parameters because they had not yet reached the optimal level (Chan et al 1998a) and the effects of the growth factor could therefore be studied.…”