function Ligaments function to restrict joint motion stabilize joint have mechanoreceptors and free nerve endings that help with joint proprioception Composition Extracellular components consist of water Type I collagen (70% of dry weight) elastin higher elastin content than tendons lipids proteoglycans epiligament coat present in some ligaments, not all analogous to epitenon of tendons Cellular component the main cell type in both tendons and ligaments is the fibroblast both tendons and ligaments have low vascularity and cellularity Ligaments vs. tendons composition compared to tendons, ligaments have lower percentage of collagen higher percentage of proteoglycans and water less organized collagen fibers rounder fibroblasts Bone insertion Two types of ligament bone insertion indirect (fibrous insertion) most common form of bone insertion superficial fibers insert into the periosteum deep fibers insert directly into bone via perforating collagen fibers called Sharpey fibers at insertion, endotenon becomes continuous with periosteum examples MCL inserting into proximal tibia direct (fibrocartilaginous insertion) has both deep and superficial fiber insertion deep fibers have four transitional zones of increasing stiffness that allow for force dissipation and reduce stress concentration Zone 1 (tendon or ligament proper) consists of well aligned type I collagen fibers with small amounts of proteoglycan decorin Zone 2 (fibrocartilage) consists of types II and III collagen, with small amounts of type I, IX and X collagen, and proteoglycans aggrecan and decorin Zone 3 (mineralized fibrocartilage) consists of type II collagen, with significant amounts of type X collagen and aggrecan Zone 4 (bone) is made up of type I collagen, with high mineral content examples supraspinatus insertion Blood Supply Origin receives blood supply at insertion site (different from tendons) ACL (and PCL) receives blood supply from middle geniculate artery have uniform microvascularity within ligament Biomechanical Properties Stress relaxation decreased stress with time under constant deformation Creep increased deformation with time under constant load Hysteresis (energy dissipation) when tissue is loaded and unloaded, the unloading curve will not follow the loading curve the difference between the 2 curves is the energy that is dissipated Stress-strain (load-elongation) curve toe region significant deformation for given load in this region, the crimped and relaxed fibers of the ligament straighted to take up load linear region fibers oriented longitudinal and parallel to load constant load-elongation stiffness = slope of load-elongation curve in this region Young's modulus of elasticity yield and failure region nonlinear yield point transition from elastic (reversible) to plastic (irreversible) deformation ultimate failure point before steep decline in load-deformation curve Ligament vs. tendons stress-strain differences between tendons and ligaments tendons carry higher loads, recruit fibers quickly smaller toe region ligaments recruit fibers gradually elongated toe region Ligament Failure Mechanism rupture of sequential series of collagen fibers ligaments do not plastically deform Failure site usually midsubstance in adults usally at bony insertion in children ligament avulsion occurs at junction of mineralized and unmineralized fibrocartilage layers Classification ligament injuries are classified into 3 grades Grade I corresponds to mild sprain Grade II corresponds to moderate sprain/partial tear Grade III corresponds to complete tear Ligament Healing Phases inflammatory phase occurs at 1-7days influx of neutrophyils and macrophages production of type III collagen growth factors involved TGF-β1 IGF PDGF BMPs -12 and -13 bFGF proliferation phase occurs at 7-21 days gradually replaced by type I collagen tendons and ligaments are weakest at day 5-21 remodeling phase occurs at >14 days maturation phase up to 18 months Factors that impair ligament healing intra-articular extra-articular ligaments (e.g. knee MCL) have a greater capacity to heal compared with intra-articular ligaments (e.g. knee ACL) increasing age immobilization reduces strength of both intact and repaired ligament smoking NSAIDS including indocin, celcoxib, parecoxib diabetes alcohol intake decreased growth factors bFGF, NGF, and IGF-1 decreased expression of genes involved with tendon and ligament healing examples include procollagen I cartilage oligomeric matrix protein (COMP) tenascin-C tenomodulin scleraxis Factors that improve ligament healing (experimental) extra-articular extra-articular ligaments (e.g. knee MCL) have a greater capacity to heal compared with intra-articular ligaments (e.g. knee ACL) compromised immune response CD44 (receptor for lymphocyte activation) knockout mice have faster patellar tendon healing Interleukin 10 (anti-inflammatory cytokine) improves patellar tendon healing in mice Interleukin 1 (inflammatory mediator) receptor antagonist inhibits loss of mechanial properties in patellar tendons in rabbits depletion of macrophages (source of TGF-β1 that stimulates fibrosis) improves ACL graft healing in mice (less scar, more fibrocartilage) mesenchymal stem cells improved healing of tendon graft in bone tunnel in rabbits and rats promote healing of partial tears of digital flexor tendons in horses insufficient for rat rotator cuff repair (shear stresses too high) growth factors PDGF-BB increases cellular proliferation and limits adhesions in dog flexor tendon repairs, but provides no improvement in tensile strength GCSF improves tendon incorporation into bone tunnels in ACL reconstruction in dogs BMP-2 and -12 improves healing in animal rotator cuff models scaffolds to help primary ligament healing (instead of reconstruction) collagen-platelet-rich plasma hydrogel helps primary ACL repair but still inferior to native ACL strength neuropeptides denervation degrades tendons and ligaments calcitonin gene-related peptide improves MCL healing in rabbits Scarring tendons and ligaments heal with scar tissue that reduces ultimate strength causes adhesions