Tendons and Ligaments

  • Function of T&L
    • Although tendons and ligaments are mechanically passive (i.e., they do not contract and produce motion as do the muscles), each plays an essential role in joint motion and stability.
    • tendons 肌腱
      • attach muscle and transmit the tensile load generated through muscular contraction or passive elongation to bone
      • produce joint motion or promote joint stability
      • contribute to maintaining body posture.
      • tendons and muscles compose the muscle tendon unit
        • acts as a dynamic restraint 动态约束
        • allow muscles to be pre-positioned at an optimal distance from joints without need for increased muscular length.
    • ligaments 韧带
      • connect bone to bone
      • augment增强 the mechanical stability of the joints
      • guide joint motion, prevent excessive过度 motion
      • Ligaments act as static restraints 静态约束
  • Tendons
    • Structure
      • The parallel arrays of collagen fibers interspersed with darker staining tenocytes/fibroblasts, The wavy or “crimp” pattern is characteristic of unloaded tendon and ligament.
    • Composition
      • basic
        • Tendons are composed of dense connective tissue
        • contains an ECM dominated by
          • parallel-fibered collagenous network 平行纤维胶原网络
          • tenocytes腱细胞(metabolically active fibroblastic cells代谢活跃的成纤维细胞)
        • In general, the cellular material occupies approximately 20% of the total tissue volume, while the ECM accounts for the remaining 80%.
      • Tenocytes 腱细胞
        • Cells within the tendon substance are specialized fibroblasts called tenocytes.
        • function
          • control tendon metabolism (production and degradation of the ECM)
          • mechanotransduction
            • respond to the mechanical stimuli applied to the tendon
            • particularly tensile loads that serve as signals for collagen production
        • shape
          • These cells lie in longitudinal rows along the collagen fibrils, following the tensile load at which they are stressed.
          • These cells have multiple extensions that stretch extensively within the extracellular matrix, allowing for three-dimensional intercellular communication via gap junctions.
          • Blocking these gap junctions in vitro体外 resulted in the cessation停止 of collagen production in response to tensile loads.
          • Tenocytes from all five species shared common characteristics with a fusiform 梭状 appearance, adherence to the flask and similar dimensions
      • ECM
        • composition
          • largely composed of a network of collagen fibers
            • Collagen
              • the collagen network is dominated by type I fibers (~60%), but other types (e. g., III, IV, V, VI) are also present .
              • Collagen type I fibers are characterized by their capacity to sustain large tensile loads while allowing for some level of compliance柔顺性 or mechanical deformation.
              • Collagen is synthesized by tenocytes in an complex process that ultimately contributes to the quality and stability of the collagen molecule
              • Cross-links are formed between collagen molecules and are essential to aggregation at the fibril level.
              • It is the cross-linked character of the collagen fibrils that gives strength to the tissues they compose and that allows these tissues to function under mechanical stress.
          • a smaller percentage of proteoglycans, elastin, and other proteins
          • 图
        • function
          • maintain the tendon’s structure
          • facilitate the biomechanical response to mechanical loading
      • Ground Substance
        • The ground substance in tendons and ligaments is composed mainly of proteoglycans (PGs 蛋白聚糖) and other proteins, accounting for <0.2% and approximately 4.5% of the weight, respectively.
        • PGs
          • PGs are macromolecules composed of various sulfated polysaccharide chains (glycosaminoglycans)
          • bonded to a core protein linked to a long hyaluronic acid (HA) chain that forms an extremely high molecular weight PG aggregate
          • PGs, such as decorin蛋白核心聚糖 and cartilage oligomatrix protein软骨寡聚基质蛋白, contribute to biomechanical and viscoelastic properties of ground substance.
          • PG与水结合
            • The PG aggregates bind most of the extracellular water of the tendon, making the matrix a highly structured gel-like material rather than an amorphous无规则 solution.
            • function
              • allows for spacing and lubrication between the collagen microfibrils
              • acts as a cement-like substance that help stabilize the collagenous skeleton of tendons肌腱的胶原骨架
              • contributes to the overall strength of these composite structures
  • Ligaments
    • Structure
      • The ECM of ligaments is also composed mainly of type I collagen
      • in contrast to tendons, the fibers are not parallel and are multidirectional
      • Most fibers- in line with the axis of the ligament
      • Some fibers- with specific orientation among the ligaments
      • Depending on the function of the ligament
    • Composition
      • elastin
        • The protein elastin is rarely present in tendons and extremity四肢 ligaments composing approximately 2-3% of the dry weight
        • but in elastic ligaments such as the ligamentum flavum黄韧带, the proportion of elastic fibers is large
        • flavum ligament黄韧带
          • elastic / collagen fibers = 2 / 1
          • connects the laminae of adjacent vertebrae
          • protect the spinal nerve roots from mechanical impingement撞击
          • pre-stress (preload) the motion segment (the functional unit of the spine)
          • provide some intrinsic stability to the spine.
      • Ligamentous Fibroblasts
        • 图
      • Ground Substance
        • The ground substance in tendons and ligaments is composed mainly of proteoglycans (PGs 蛋白聚糖) and other proteins, accounting for <0.2% and approximately 4.5% of the weight, respectively.
        • PGs
          • PGs are macromolecules composed of various sulfated polysaccharide chains (glycosaminoglycans)
          • bonded to a core protein linked to a long hyaluronic acid (HA) chain that forms an extremely high molecular weight PG aggregate
          • PGs, such as decorin蛋白核心聚糖 and cartilage oligomatrix protein软骨寡聚基质蛋白, contribute to biomechanical and viscoelastic properties of ground substance.
          • PG与水结合
            • The PG aggregates bind most of the extracellular water of the tendon, making the matrix a highly structured gel-like material rather than an amorphous无规则 solution.
            • function
              • allows for spacing and lubrication between the collagen microfibrils
              • acts as a cement-like substance that help stabilize the collagenous skeleton of tendons肌腱的胶原骨架
              • contributes to the overall strength of these composite structures
    • Outer Structure and Insertion into Bone
      • 图
  • Biomechanical Properties of T&L
    • 既能承受拉伸又有柔韧性
      • Tendons and ligaments are viscoelastic structures with unique mechanical properties
      • Tendons
        • strong enough to sustain the high tensile forces that result from muscle contraction during joint motion
        • yet they are sufficiently flexible to angulate around bone surfaces and to deflect beneath retinacula to change the final direction of muscle pull
      • Ligaments
        • pliant柔软 and flexible, allowing natural movement of the bones to which they attach
        • but are strong and inextensible不易伸长 so as to offer suitable resistance to applied forces.
    • 主要承受拉伸
      • Both structures sustain mainly tensile loads during normal and excessive loading.
      • Strong in tension
      • Little resistance to compression
      • The large slenderness ratio长细比 makes it easy for them to buckle弯曲 under compressive loads
    • viscoelastic
      • 加载力的速度快时候弹性模量更大
      • With higher strain rates, tendons and ligaments require more force to rupture, and undergo greater elongation
      • When injury happens, the degree of damage is related to the rate of loading as well as the amount of load
    • tensile testing
      • 图
      • In tensile testing of a human ligamentum flavum黄韧带, elongation of the specimen reached 50% before the stiffness increased appreciably.
      • At 70% elongation the ligament exhibited a great increase in stiffness with additional loading and failed abruptly without further deformation.
      • The greater proportion of elastic proteins and the resultant elastic capacity of the ligament results then in a larger capacity to elongate before failure (large strain to failure).
    • 能量消耗
      • The proportion of elastic proteins in ligaments and capsules关节囊 is extremely important for
        • 1.the small elastic deformation that they endure under tensile strain
        • 2.the storage and loss of energy.
      • During the loading and unloading of a ligament between two limits of elongation, the elastic fibers allow the material to return to its original shape and size after being deformed.
      • Part of the energy spent is stored.
      • What remains represents the energy loss during the cycle and is called hysteresis.
      • The area enclosed by the loop represents the energy loss.
  • Injury of T&L
    • two general categories or combination
      • high levels of stress or load
      • high rates of strain
      • high levels of both stress and strain
    • 2种损伤
      • When a ligament in vivo is subjected to loading that exceeds the physiologic range (injury due to high levels of stress)
      • microfailure takes place even before the yield point is reached (i.e., partial rupture of a ligament) yield point
      • if the yield point is exceeded, the ligament will undergo gross failure (complete rupture)
    • 运动过度→塑性形变→微损伤→炎症
    • 从下到上对应1234阶段,1常规测试时候所受力不会造成损伤,后续运动造成微损伤最终撕裂
    • 韧带损伤的三级损伤标准
    • healing
      • The healing process of ligaments is quite slow due to the limited vascularity
      • 治愈过程,最终治愈也只有10%-20%性能
  • Factors that Affect the Biomechanical Properties of T&L
    • Maturation and aging
      • During maturation成熟, cross-links strengthen tendons and ligaments, enhancing tensile strength
      • With aging, collagen’s mechanical properties declines
    • Mobilization and Immobilization
      • Ligaments adapt to stress, strengthening with increased loads and weakening with reduced stress or immobilization
    • Pharmacologic agents 药物影响
      • Steroids inhibit collagen synthesis, affecting healing and reducing peak tissue load
      • NSAIDs, like indomethacin and diclofenac, help treat ligament inflammation
    • Dietary
      • The uptake of vitamins (C, D, E), protein, and zinc is crucial for maintaining the biomechanical function of ligaments
  • Case Studies
    • Case Study 1
      • The regulation of tendon stem cell differentiation by the alignment of nanofibers
      • Biomaterials, 2010
      • Main idea
        • Nanofiber alignment provides topographical cues that regulate tendon stem cell differentiation.
        • aligned nanofibers vs random nanofibers
        • 纤维方向本身就是细胞命运信号, 细胞会沿着材料结构改变形态和表达
      • Electrospinning setup
        • syringe with polymer solution
        • needle and liquid jet
        • high voltage power supply
        • Taylor cone
        • collector
      • Cell morphology
        • On aligned fibers, cells become elongated and oriented along the fiber direction.
        • On random fibers, cells spread with less directional organization.
        • 图 - SEM shows aligned vs random nanofiber networks; fluorescence images show different cell shapes
      • Gene expression trends
        • SCX scleraxis, a tenogenic marker, is higher on aligned nanofibers at 3d and 7d.
        • RUNX2 and ALP are higher on random nanofibers, suggesting more non-tenogenic or osteogenic tendency.
        • Integrin α1, integrin β1, integrin α5, and myosin II respond to nanofiber alignment.
        • 图 - aligned/random comparison shows material architecture changes tendon stem cell marker expression
    • Case Study 2
      • Cyclic tensile strain upregulates collagen synthesis in isolated tendon fascicles
      • Biochemical and Biophysical Research Communications, 2005
      • Experimental setup
        • isolated fascicle mounted in a chamber
        • medium surrounding the fascicle
        • Perspex grips and 15 mm gauge length
        • load cell
        • loading arm connected to actuator
      • Mechanical stimulus
        • cyclic tensile strain applied to tendon fascicles
        • compared with unstrained controls
      • Matrix synthesis readouts
        • sulfate incorporation increased with strain by 7.9%
        • proline incorporation increased with strain by 25.1%
        • proline incorporation is a collagen synthesis-related signal
        • 机械拉伸会让 tendon fascicle 更积极合成基质, 尤其是 collagen 相关合成
    • Case Study 3
      • Multifunctional tendon-mimetic hydrogels
      • Science Advances, 2023
      • Design logic
        • anisotropic assembly of aramid nanofiber composites
        • stiff aramid nanofibers mimic aligned collagen fibers
        • soft polyvinyl alcohol (PVA) mimics proteoglycan-rich soft matrix
        • 硬纤维 + 软基质, 模仿肌腱里 collagen fibers 和 PG matrix 的组合
      • Fabrication route
        • random network
        • stretching
        • confined drying
        • reswelling
        • isotropic network becomes oriented structure
      • Reported properties
        • modulus about 1.1 GPa
        • strength about 72 MPa
        • fracture toughness 7333 J/m^2
        • properties approach natural tendon more closely than previous synthetic hydrogels
      • Added functions
        • printed bioelectronic connections
        • biofunctionalization for cell interface
        • cell alignment on ACH-80 surface
        • 图 - oriented hydrogel structure and aligned cells show tendon-mimetic anisotropy
  • Take-Home Message
    • What is the major composition of tendons and ligaments?
      • Answer EN
        • Tendons and ligaments are dense connective tissues composed mainly of extracellular matrix and fibroblastic cells.
        • The ECM is dominated by collagen, mostly type I collagen.
        • Tendons contain about 75-85% collagen, < 3% elastin, and 1-2% proteoglycans.
        • Ligaments contain about 70-80% collagen, elastin, proteoglycans, and resident ligamentous fibroblasts.
        • Ground substance contains PG aggregates that bind water, lubricate collagen microfibrils, and stabilize the collagen skeleton.
      • 回答 中文
        • 肌腱和韧带主要是胶原为主的 ECM 加少量细胞
        • 肌腱细胞叫 tenocytes, 韧带里有 ligamentous fibroblasts
        • 胶原主要负责抗拉, PG 和水形成凝胶样基质, 帮助润滑和稳定纤维骨架
    • What are the structural properties of tendons and ligaments?
      • Answer EN
        • Tendons have parallel-fibered collagen networks aligned with the main tensile loading direction.
        • Unloaded tendons and ligaments show a wavy crimp pattern that straightens during loading.
        • Tenocytes lie in longitudinal rows along collagen fibrils and communicate through gap junctions.
        • Ligaments contain mainly type I collagen but their fibers are more multidirectional than tendon fibers.
        • Insertion into bone is graded through parallel collagen fibers, unmineralized fibrocartilage, mineralized fibrocartilage, and cortical bone.
      • 回答 中文
        • 肌腱胶原纤维更平行, 适合单向传递肌肉拉力
        • 韧带胶原方向更多样, 适合按关节运动方向限制过度运动
        • unloaded 状态的 crimp 波纹先被拉直, 这是早期变形的重要来源
        • 肌腱/韧带插入骨的位置有纤维软骨过渡层, 用来减少软硬交界处应力集中
    • What is the relationship between the structure and respective function of tendons and ligaments?
      • Answer EN
        • Tendons connect muscle to bone and transmit tensile load, so their collagen fibers are highly aligned and strong in tension.
        • Tendons are also flexible enough to wrap or deflect around anatomical structures and redirect muscle pull.
        • Ligaments connect bone to bone, guide joint motion, and prevent excessive motion.
        • Ligament fiber orientation is more multidirectional and function-dependent, allowing joint restraint in specific directions.
        • Elastic components in ligaments, especially ligamentum flavum, allow large elongation and energy storage before failure.
      • 回答 中文
        • 肌腱是传力绳, 所以结构强调平行胶原和抗拉强度
        • 韧带是限位带, 所以结构强调按关节运动方向布置纤维
        • 黄韧带 elastin 多, 所以能大幅伸长并帮助脊柱保持稳定
    • Which factors may affect the biomechanical properties of tendons and ligaments?
      • Answer EN
        • Maturation strengthens tendons and ligaments by increasing cross-links and tensile strength.
        • Aging reduces collagen mechanical properties.
        • Mobilization and increased loads strengthen ligaments, while reduced stress or immobilization weakens them.
        • Steroids inhibit collagen synthesis, affect healing, and reduce peak tissue load.
        • NSAIDs such as indomethacin and diclofenac help treat ligament inflammation.
        • Vitamins C, D, E, protein, and zinc are important for maintaining biomechanical function.
        • Loading rate also matters: higher strain rate increases force required for rupture and increases stress-strain slope.
      • 回答 中文
        • 成熟、交联、合理加载会让肌腱韧带更强
        • 衰老、固定不用、激素抑制胶原合成会让组织变弱或愈合变差
        • 营养和抗炎药物会影响修复环境
        • 加载速度也重要, 拉得越快组织表现得越硬, 损伤风险和破裂模式也会变