Collagen fibre and fibril ultrastructural arrangement of the superficial medial collateral ligament in the human knee.

PURPOSE: The aim of the study was to investigate the collagen fibre ultrastructural arrangement and collagen fibril diameters in the superficial medial collateral ligament (sMCL) in the human knee. Considering sMCL's distinctive functions at different angles of knee flexion, it was hypothesized a significant difference between the collagen fibril diameters of each portion of the sMCL. METHODS: Fourteen sMCL from seven fresh males (by chance because of the availability) cadavers (median age 40 years, range 34-59 years) were harvested within 12 h of death. sMCLs were separated into two orders of regions for analysis. The first order (divisions) was anterior, central and posterior. Thereafter, each division was split into three regions (femoral, intermediate and tibial), generating nine portions. One sMCL from each cadaver was used for transmission electron microscopy (TEM) and morphometric analyses, whereas the contralateral sMCL was processed for light microscopy (LM) or scanning electron microscopy (SEM). RESULTS: LM and SEM analyses showed a complex tridimensional architecture, with the presence of wavy collagen fibres or crimps. TEM analysis showed significant differences in median collagen fibril diameter among portions inside the anterior, central and posterior division of the sMCL (p < 0.0001 within each division). Significant differences were also present among the median [interquartile range] collagen fibril diameters of anterior (39.4 [47.8-32.9]), central (38.5 [44.4-34.0]) and posterior (41.7 [52.2-35.4]) division (p = 0.0001); femoral (38.2 [45.0-32.7]), intermediate (40.3 [47.3-36.1]) and tibial (40.7 [55.0-32.2]) region (p = 0.0001). CONCLUSIONS: Human sMCL showed a complex architecture that allows restraining different knee motions at different angles of knee flexion. The posterior division of sMCL accounted for the largest median collagen fibril diameter. The femoral region of sMCL accounted for the smallest median collagen fibril diameter. The presence of crimps in the medial collateral ligament, previously identified in the rat, was confirmed in humans (taking into consideration differences between these two species).

Quantification of collagen organization using fractal dimensions and Fourier transforms.

Collagen fibers and fibrils that comprise tendons and ligaments are disrupted or damaged during injury. Fibrillogenesis during healing produces a matrix that is initially quite disorganized, but remodels over time to resemble, but not replicate, the original roughly parallel microstructure. Quantification of these changes is traditionally a laborious and subjective task. In this work we applied two automated techniques, fast Fourier transformation (FFT) and fractal dimension analysis (FA) to quantify the organization of collagen fibers or fibrils. Using multi-photon images of collagen fibers obtained from rat ligament we showed that for healing ligaments, FA differentiates more clearly between the different time-points during healing. Using scanning electron microscopy images of overstretched porcine flexor tendon, we showed that combining FFT and FA measures distinguishes the damaged and undamaged groups more clearly than either method separately.

Collagen fibre arrangement and functional crimping pattern of the medial collateral ligament in the rat knee.

Ligaments have been described as multifascicular structures with collagen fibres cross-connecting to each other or running straight and parallel also showing a waviness or crimping pattern playing as a shock absorber/recoiling system during joint motions. A particular collagen array and crimping pattern in different ligaments may reflect different biomechanical roles and properties. The aim of the study was to relate the 3D collagen arrangement in the crimping pattern of the medial collateral ligament (MCL) to its functional role. The MCL is one of the most injured ligaments during sports activities and an experimental model to understand the rate, quality and composition of ligaments healing. A deep knowledge of structure-function relationship of collagen fibres array will improve the development of rehabilitation protocols and more appropriate exercises for recovery of functional activity. The rat MCL was analysed by polarized light microscopy, confocal laser microscopy and scanning electron microscopy (SEM). Histomorphometric analysis demonstrated that MCL crimps have a smaller base length versus other tendons. SEM observations demonstrated that collagen fibres showing few crimps were composed of fibrils intertwining and crossing one another in the outer region. Confocal laser analyses excluded a helical array of collagen fibres. By contrast, in the core portion, densely packed straight collagen fibres ran parallel to the main axis of the ligament being interrupted both by planar crimps, similar to tendon crimps, and by newly described right-handed twisted crimps. It is concluded that planar crimps could oppose or respond exclusively to tensional forces parallel to the main ligament axis, whereas the right-handed twisted crimps could better resist/respond to a complex of tensional/rotational forces within the ligament thus opposing to an external rotation of tibia.

Transversely isotropic distribution of sulfated glycosaminoglycans in human medial collateral ligament: a quantitative analysis.

Decorin and its associated glycosaminoglycan (GAG) side chain, dermatan sulfate (DS), play diverse roles in soft tissue formation and potentially aid in the mechanical integrity of the tissue. Deeper understanding of the distribution and orientation of the GAGs on a microscopic level may help elucidate the structure/function relationship of these important molecules. The hypothesis of the present study was that sulfated GAGs are aligned with transversely isotropic material symmetry in human medial collateral ligament (MCL) with the collagen acting as the axis of symmetry. To test the hypothesis, sulfated GAGs were visualized using transmission electron microscopy (TEM). Three orthogonal anatomical planes were examined to evaluate GAG distributions against symmetry criteria. GAG populations were differentiated using targeted enzyme digestion. Results suggest that sulfated GAGs including DS, chondroitin sulfates A and C, as well as other sub-populations assume transversely isotropic distributions in human MCL. Sulfated GAGs in the plane normal to the collagen axis were found to be isotropic with no preferred orientation. GAGs in the two planes along the collagen axis did not statistically differ and exhibited apparent bimodal distributions, favoring orthogonal distributions with over half at other angles with respect to collagen. A previously developed model, GAGSim3D, was used to interpret potential TEM artifacts. The data collected herein provide refined inputs to micro-scale models of the structure/function relationship of sulfated GAGs in soft tissues.

Response of knee ligaments to prolotherapy in a rat injury model.

BACKGROUND: Prolotherapy is an alternative therapy for chronic musculoskeletal injury including joint laxity. The commonly used injectant, D-glucose (dextrose), is hypothesized to improve ligament mechanics and decrease pain through an inflammatory mechanism. No study has investigated the mechanical effects of prolotherapy on stretch-injured ligaments. HYPOTHESES: Dextrose injections will enlarge cross-sectional area, decrease laxity, strengthen, and stiffen stretch-injured medial collateral ligaments (MCLs) compared with controls. Dextrose prolotherapy will increase collagen fibril diameter and density of stretch-injured MCLs. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-four rats were bilaterally MCL stretch-injured, and the induced laxity was measured. After 2 weeks, 32 MCLs were injected twice, 1 week apart, with either dextrose or saline control; 16 MCLs received no injection. Seven uninjured rats (14 MCLs) were additional controls. Two weeks after the second injection, ligament laxity, mechanical properties (n = 8), and collagen fibril diameter and density (n = 3) were assessed. RESULTS: The injury model created consistent ligament laxity (P < .05) that was not altered by dextrose injections. Cross-sectional area of dextrose-injected MCLs was increased 30% and 90% compared with saline and uninjured controls, respectively (P < .05). Collagen fibril diameter and density were decreased in injured ligaments compared with uninjured controls (P < .05), but collagen fibril characteristics were not different between injured groups. CONCLUSION: Dextrose injections increased the cross-sectional area of MCLs compared with saline-injected and uninjured controls. Dextrose injections did not alter other measured properties in this model. CLINICAL RELEVANCE: Our results suggest that clinical improvement from prolotherapy may not result from direct effects on ligament biomechanics.

Effects of a bioscaffold on collagen fibrillogenesis in healing medial collateral ligament in rabbits.

Bioscaffolds have been successfully used to improve the healing of ligaments and tendons. In a rabbit model, the application of porcine small intestine submucosa (SIS) to the healing medial collateral ligament (MCL) resulted in improved mechanical properties with the formation of larger collagen fibrils. Thus, the objective of the study was to find out whether the SIS bioscaffold could improve the gene expressions of fibrillogenesis-related molecules, specifically, collagen types I, III, V, and small leucine-rich proteoglycans including decorin, biglycan, lumican, and fibromodulin, as well as collagen fibril morphology and organization, in the healing rabbit MCL at an early time point (6 weeks postinjury). Twenty skeletally mature rabbits were equally divided into two groups. In the SIS-treated group, a 6-mm gap was surgically created and a layer of SIS was sutured to cover the gap, whereas the gap was left open in the nontreated group. At 6 weeks postinjury, Masson's trichrome staining showed that the SIS-treated group had more regularly aligned collagen fibers and cells. Transmission electron microscopy revealed that the SIS-treated group had larger collagen fibrils with a diameter distribution from 24 to 120 nm, whereas the nontreated group had only small collagen fibrils (ranging from 26 to 87 nm, p < 0.05). Finally, the quantitative real-time PCR showed that the mRNAs of collagen type V, decorin, biglycan, and lumican in the SIS-treated group were 41, 58, 51, and 43% lower than those in the nontreated group, respectively (p < 0.05). Such significant reduction in the gene expressions are closely related to the improved morphological characteristics, which are known to be coupled with better mechanical properties, as previously reported in longer term studies.

Systemic vanadate ingestion improves early medial collateral ligament repair.

The medial collateral ligament (MCL) of the knee is frequently injured in sport. Repair is slow and often complicated by scar formation which may result in impairment of function. Vanadate is a promising efficacious treatment for tissue injuries and this study aimed to examine its effect in rats on the histological and biomechanical features of MCL healing. Rats received either 0.025 g/kg per day vanadate or equivalent amounts of drinking water (control) by intragastric gavage for 1 week before and 2 weeks after wounding. Repaired sites were dissected out for histological and biomechanical tests 28 days after wounding. Fibre bundles in the vanadate-treated group were uniform and evenly spaced. Furthermore, vanadate significantly increased the diameter of collagen fibrils in the healing tissue. Stiffness and ultimate force of the femur-medial collateral ligament-tibia complex for the vanadate-treated group were significantly higher than for the controls. The results suggest that vanadate significantly improves the histological and biomechanical properties of healing MCL.

Effect of low-level laser therapy on healing of medial collateral ligament injuries in rats: an ultrastructural study.

OBJECTIVE: This study sought to investigate whether low-level laser therapy (LLLT) with a helium-neon (He-Ne) laser would increase fibril diameter of transected medial collateral ligament (MCL) in rats. BACKGROUND DATA: It has been shown that LLLT can increase ultimate tensile strength MCL healing. METHODS: Thirty rats received surgical transect to their right MCL, and five were assigned as the control group. After surgery, the rats were divided into three groups: group 1 (n = 10) received LLLT with He-Ne laser and 0.01 J/cm(2) energy fluency per day, group 2 (n = 10) received LLLT with 1.2 J/cm(2) energy fluency (density) per day and group 3 (sham-exposed group; n = 10) received daily placebo laser with shut-down laser equipment, while control group received neither surgery nor LLLT. Transmission electron microscope (TEM) examination was performed on days 12 and 21 after surgery and dimension and density of ligament fibrils were measured. The data were analyzed by Student t-test and Mann-Whitney tests, respectively. RESULTS: On day 12, the fibril dimension of group 2 and their density were higher than of groups 1 and 3. CONCLUSION: LLLT with He-Ne laser on incised MCL in rats could not significantly increase fibril diameter and their density in comparison with sham-exposed group.

Effect of dermatan sulfate glycosaminoglycans on the quasi-static material properties of the human medial collateral ligament.

The glycosaminoglycan of decorin, dermatan sulfate (DS), has been suggested to contribute to the mechanical properties of soft connective tissues such as ligaments and tendons. This study investigated the mechanical function of DS in human medial collateral ligaments (MCL) using nondestructive shear and tensile material tests performed before and after targeted removal of DS with chondroitinase B (ChB). The quasi-static elastic material properties of human MCL were unchanged after DS removal. At peak deformation, tensile and shear stresses in ChB treated tissue were within 0.5% (p>0.70) and 2.0% (p>0.30) of pre-treatment values, respectively. From pre- to post-ChB treatment under tensile loading, the tensile tangent modulus went from 242+/-64 to 233+/-57 MPa (p=0.44), and tissue strain at peak deformation went from 4.3+/-0.3% to 4.4+/-0.3% (p=0.54). Tissue hysteresis was unaffected by DS removal for both tensile and shear loading. Biochemical analysis confirmed that 90% of DS was removed by ChB treatment when compared to control samples, and transmission electron microscopy (TEM) imaging further verified the degradation of DS by showing an 88% reduction (p<.001) of sulfated glycosaminoglycans in ChB treated tissue. These results demonstrate that DS in mature knee MCL tissue does not resist tensile or shear deformation under quasi-static loading conditions, challenging the theory that decorin proteoglycans contribute to the elastic material behavior of ligament.

Tendons and ligaments are anatomically distinct but overlap in molecular and morphological features--a comparative study in an ovine model.

Tendons and ligaments are similar in composition but differ in function. Simple anatomical definitions do not reflect the fact individual tendons and ligaments have unique properties due to their adaptation to a specific role. The patellar tendon is a structure of particular clinical interest. A null hypothesis was declared stating that the patellar tendon is not significantly different in terms of matrix composition and collagen fibril diameter to other tendons. The lateral and medial collateral ligaments (LCL, MCL), anterior and posterior cruciate ligaments (ACL, PCL), together with the long digital extensor, superficial digital extensor, and patellar tendons (LDET, SDFT, PT) were harvested from three cadaveric ovine hindlimbs. The extracellular matrix was assessed in terms of water, collagen, and total sulphated glycosaminoglycan (GAG) content. The organization of the collagen component was determined by an ultrastructural analysis of collagen fibril diameter distributions, together with values for the collagen fibril index (CFI) and mass-average diameter (MAD). There were significant differences between ligaments and tendons. The PT had a bimodal collagen fibril diameter distribution with CFI 72.9%, MAD 202 nm, water content 53.1%, GAG content 2.3 microg/mg, and collagen content 73.7%, which was not significantly different from the other tendons. The results of this study support the null hypothesis suggesting that the patellar tendon is similar to other tendons and demonstrate that tendons have different characteristics to ligaments.

Treatment with bioscaffold enhances the the fibril morphology and the collagen composition of healing medial collateral ligament in rabbits.

Porcine small intestinal submucosa (SIS) was shown to be an effective bioscaffold in enhancing the mechanical properties of healing medial collateral ligaments (MCL). The purpose of this study was to investigate whether there are corresponding improvements in morphology and tissue compositions. Fourteen rabbits were equally divided into two groups. In the SIS-treated group, a 6 mm gap was surgically created in the right MCL and a layer of SIS was sutured covering the gap. For the nontreated group, the gap-injured MCLs remained untreated. All the left MCLs were sham operated and used as controls. At 12 weeks, the status of collagen types I and V was evaluated with immunofluorescent staining. The collagen type V/I ratios were obtained using SDS-PAGE. Collagen fibril diameters were calculated from the transmission electron micrographs. The results revealed that in the SIS-treated group, the collagen fibers were more regularly aligned as were the cell nuclei. The collagen fibril diameters were 22.2% larger and the ratio of collagen type V/I was 28.4% lower than those for the nontreated group (p < 0.05). These improvements in the morphological characteristics and biochemical constituents of healing MCLs following SIS treatment are the likely reasons for improved mechanical properties.

Vanadate ingestion enhances the organization and collagen fibril diameters of rat healing medical collateral ligaments.

Although an injured medial collateral ligament (MCL) will naturally heal, the quality of healing tissue is inferior to the uninjured MCL tissue. Previous studies have shown promising results of sodium orthovanadate (vanadate) in enhancing the quality of rat skin wounds. This study therefore investigated whether vanadate enhances the quality of the rat healing MCL in terms of the collagen fibril organization and diameter. Six mature male Sprague-Dawley rats, with weight ranges of 475-505 g and ages of 25 weeks, were used in this study. Three rats in the experimental group received vanadate (0.2 mg/ml) in their saline drinking water (150 mM NaCl), whereas three rats in the control group were only given saline water. Three weeks after transection, the rat MCLs were harvested for hematoxylin and eosin (H&E) staining and transmission electron microscopy. It was found that vanadate promoted organization of collagen fibrils and significantly increased the diameters of collagen fibrils by 14% in healing MCL (P<0.001). These results indicate that application of vanadate may be a promising tissue engineering approach to enhance the quality of healing tissues such as injured MCLs.

Gap junctions of the medial collateral ligament: structure, distribution, associations and function.

Ligaments are composed of two major components: cells and extracellular matrix. The cells express gap junction proteins and are arranged into a series of rows that traverse the tissue, suggesting that all the cells of the tissue are functionally interconnected. The results of our study demonstrate that medial collateral ligament (MCL) cells do not have a uniform fusiform morphology or placement along a row of cells as previously suggested, but rather display a complex placement and form that weaves within the collagen matrix in a manner that is far more extensive and complex than previously appreciated. Within this morphological context, we find that MCL cells in vivo contain functional gap junctions (verified using fluorescence recovery after photobleaching) that are localized to sites of close cell-cell contact, and this pattern imparts or reflects a bipolarity inherent to each cell. When we studied ligament cells in conventional tissue culture we found that this bipolarity is lost, and the placement of gap junctions and their related proteins, as well as general cell morphology, is also altered. Finally, our study demonstrates, for the first time, that in addition to gap junctions, adherens junctions and desmosomes are also expressed by MCL cells both in vivo and in vitro and map to sites of cell-cell contact.

Effects of herbal application on the ultrastructural morphology of repairing medial collateral ligament in a rat model.

The present study investigated the effects of an external herbal application on the ultrastructural morphology of repairing medial collateral ligament (MCL) in a rat model. Eight MCL-transected/herb-treated rats (group 1) were compared with 8 MCL-transected/placebo-treated controls (group 2) and 8 MCL-intact/placebo-treated rats (group 3). At 3 and 6 weeks posttransection, MCL specimens were examined under electron microscope. With analysis of 370,709 collagen fibrils, all herb-treated animals had significantly larger fibrils than the controls (p < .001) at 6 weeks postinjury. The mean diameter of those peripheral collagen fibrils of group 1 was larger than the sham group (p < .001). The mass-averaged diameters of group 1 (50.49 to 143.07 nm) and group 3 (59.69 to 188.88 nm) were larger than group 2 (50.59 to 121.94 nm). The area coverage by collagen fibrils ranged from 46.86 to 94.97% for group 1 and 43.70 to 68.08%f or group 3 as compared with 40.01 to 50.77% for group 2. Mode obliquity was 0.56 to 0.84 among groups. We concluded that herbal remedy increases collagen fibril size of healing rat MCLs homogeneously at 6 weeks posttransection.

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

BACKGROUND AND OBJECTIVES: Low energy laser therapy has been shown to enhance mechanical strength of healing medial collateral ligament (MCL) in rats. The present study investigated its effects on the ultrastructural morphology and collagen fibril profile of healing MCL in rats. STUDY DESIGN/MATERIALS AND METHODS: Thirty-two mature male Sprague-Dawley (SD) rats were used. Twenty-four underwent surgical transection to their right MCLs and eight received only skin wound. Immediately after surgery, eight of the MCL transected rats were treated with a single dose of laser therapy at 63.2 J cm(-2), eight were treated with a single dose of laser therapy at 31.6 J cm(-2), the rest had no treatment and served as control. At 3 and 6 weeks after surgery, the MCLs were harvested and examined with electron microscopy for collagen fibril size, distribution, and alignment. RESULTS: Significant differences (P < 0.001) were found in fibril diameters from the same anatomical site and time period among different groups. The mass-averaged diameters of the laser-treated (64.99-186.29 nm) and sham (64.74-204.34 nm) groups were larger than the control group (58.66-85.89 nm). The collagen fibrils occupied 42.55-59.78, 42.63-53.94, and 36.92-71.64% of the total cross-sectional areas in the laser-treated, control and sham groups, respectively. Mode obliquity was 0.53-0.84 among the three groups. CONCLUSIONS: Single application of low energy laser therapy increases the collagen fibril size of healing MCLs in rats.

The cellular networks of normal ovine medial collateral and anterior cruciate ligaments are not accurately recapitulated in scar tissue.

The purpose of this study was to characterize the cellular organization of the ovine medial collateral ligament (MCL) and anterior cruciate ligament (ACL) and compare this organization with that found in ligaments undergoing healing. Indirect immunofluorescence microscopy, used in combination with antibodies to cytoskeletal proteins, was employed to visualize individual ligament cells. Normal ligaments contained fusiform cells arranged in rows, which were stacked at regular intervals across the body of the ligament forming a three-dimensional cellular lattice. Each cell exhibited prominent cytoplasmic processes that extended for long distances through the extracellular matrix to adjacent cells, and these processes contained gap junctions. Thus the cells in rows and between rows were interconnected. The cells of the MCL and ACL scars were also arranged in rows, but these rows were shorter, irregularly arranged and closely packed into bundles resulting in tissue with a higher cellular density. In addition, cells transiting the cell cycle were detected in the scar but not in normal ligament. While the rows of cells in the normal ligament extended along the long axis of the ligament, the bundles of rows of ligament scar cells had a random orientation with respect to one another and to the region outside the scar. Over time both the ACL and the MCL scars displayed discontinuities in their cellular rows. In contrast to the scars of the MCL, which contained discontinuities filled with cellular projections and gap junctions, ACL scars contained discontinuities that were devoid of cells and gap junctions. These discontinuities as well as the differences between normal and scar cytoarchitecture may represent features of an inadequate healing response and/or may provide the structural basis for the altered biomechanics of healing ligaments.

Collagen fibril diameters in the rabbit medial collateral ligament scar: a longer term assessment.

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.

Decrease in fibronectin occurs coincident with the increased expression of its integrin receptor alpha5beta1 in stress-deprived ligaments.

Stress deprivation secondary to immobilization leads to atrophic changes in periarticular soft tissues. The changes in ligaments include a disorganization of collagen and cellular ultrastructure with varied biochemical alterations resulting in a functionally weaker tissue. This study tests the hypothesis that alterations in fibronectin (Fn) and the expression of its integrin receptor alpha5beta1 in ligament fibroblasts accompany the extracellular matrix remodeling which occurs in stress-deprived knee ligaments. The left knees of eighteen New Zealand white rabbits were surgically immobilized in acute flexion. Fibroblasts within three nine week and three twelve week stress-deprived anterior cruciate ligaments (ACLs) and medial collateral ligaments (MCLs) demonstrated markedly increased immunostaining for the beta1 and alpha5 integrin subunits, as compared to fibroblasts in the contralateral unoperated control ligaments. The effects of stress deprivation on the concentration of Fn was measured by competitive ELISA on the remaining twelve rabbits. Decreases in Fn of 54.0 percent and 63.7 percent occurred in the ACL after nine and twelve weeks of stress deprivation when compared to contralateral controls. The MCL had less of a decrease, losing 37.7 percent and 41.7 percent at nine and twelve weeks, respectively. These results suggest an important role for the Fn-specific integrin receptor alpha5beta1 in remodeling stress-deprived periarticular ligamentous tissue, and the importance of maintaining normal stresses on periarticular ligaments to prevent the degradation of extracellular matrix components such as Fn.

Changes in the distribution of fibrillar collagens in the collateral and cruciate ligaments of the rabbit knee joint during fetal and postnatal development.

The collateral ligaments can be clearly distinguished in the 25-day fetal rabbit knee joint. Type I and V collagens are present in the extracellular matrix between the cells of the lateral and medial collateral ligaments and this distribution persists until the rabbit is skeletally mature. From 8 months onwards type III collagen is also present, particularly around the cells. Type I collagen mRNA is expressed by the cells from the 25-day fetal to 8-month-old adult ligament. The ligament sheath is composed of types III and V collagens. The cruciate ligaments are present between the femur and tibia in the 20-day fetus. The matrix is composed of types I and V collagens from the 25-day fetus until at 12- to 14-weeks postnatal, type III collagen appears in the pericellular regions together with type V. At 8 months and 2 years the amount of type III collagen has increased. All the cells express the mRNA for type I collagen at 12- to 14-weeks, but only isolated cells express this mRNA at 8 months. Thus, both the collateral and cruciate ligaments undergo changes in their complement of collagens during postnatal development and ageing. The implications of these complex interactions of different types of collagen are discussed in relation to healing and the surgical replacement of torn ligaments by tendons.