Biomechanics of Articular Cartilage PDF

Biomechanics of articular cartilage 1. Composition and structure of articular cartilage CARTILAGE: - White, solid, resistant and elastic connective tissue, specialized in the support and movement of the body - It doesn't contain vessels and nerves - Functions: - Movement of bones in...

Biomechanics of articular cartilage 1. Composition and structure of articular cartilage CARTILAGE: - White, solid, resistant and elastic connective tissue, specialized in the support and movement of the body - It doesn't contain vessels and nerves - Functions: - Movement of bones in joints - Flexible but strong framework of some organs - Mold on which long bones are formed TYPES OF CARTILAGE: - Hyaline cartilage (articular cartilage): - More abundant - Few cells and fibers - Surrounded by perichondrium - Elastic cartilage: - Numerous and large chondrocytes - Predominance of elastic fibers - Surrounded by perichondrium - Fibrous cartilage: - Intermediate characteristics between dense connective tissue and hyaline cartilage - Chondrocytes in a roe - Collagen I and II - Without perichondrium. COMPONENTS OF ARTICULAR CARTILAGE: - Extracellular matrix: - Fibers - Ground substance - Cells: - Chondrogenic cells - Chondroblasts - Chondrocytes - Perichondrium: connective tissue MESENCHYMAL ORIGIN: STRUCTURE OF ARTICULAR CARTILAGE: - Surface zone: elongated chondrocytes and collagen arranged parallel to the surface - Intermediate zone: chondrocytes arranged without any order - Deep zone: chondrocytes arranged in linear isogeneous groups and collagen perpendicular to the surface - Calcified zone: calcified matrix LOCALIZATION OF HYALINE CARTILAGE: - Fetus: - Skeleton - Childhood-adolescence: - Growth plates - Adulthood: - Nasal septum - Larynx - Trachea and bronchi - Costal cartilages - Surface of mobile joints. For example: knee, ankle, hip… 2. Biomechanical behaviour of lubrication of articular cartilage LUBRICATION OF THE ARTICULAR CARTILAGE: - Process by which friction between two moving parts is reduced by introducing a fluid to separate the two contact surfaces - Two mechanisms: - Barrier lubrication: lubricin (glycoprotein) is absorbed as a monolayer for each articular surface - Film-fluid lubrication: greater separation of the surfaces and supports the load FILM-FLUID LUBRICATION OF THE ARTICULAR CARTILAGE: - Hydrodynamic lubrication: - Lead bearing surfaces slide against each other forming a fluid conversion - Separation of the surfaces  - Film-press lubrication: - Articular surfaces move perpendicular to each other generating a viscous resistance of the fluid that prevents its scape from the space - Supporting high loads for a short duration. “MIXED LUBRICATION” OF THE ARTICULAR CARTILAGE: - Low contact areas: - Film-fluid lubrication4 - Areas of greater friction: - Both, but with the predominance of barrier lubrication. VISCOELASTIC RESPONSE - Viscoelasticity is a type of behaviour exhibited by certain materials that present both viscous and elastic properties when deformed - Cartilage is capable of undergoing a constant load, responding with a rapid initial deformation that becomes slow and progressive over time - Liquid → Solid 3. Wear of articular cartilage - Wear: imbalance between synthesis and degradation processes in the extracellular matrix → Progressive loss of cartilage tissue - Load and movement: requirement for the development, renewal and maintenance of cartilage and joint integrity - Constant join load → reduction in cartilage thickness - Upon cessation of activity → joint unloaded and hydrostatic pressure re-established FACTORS CONTRIBUTING TO WEAR: - Overweight: - Increase of the force through the joint inducing cartilage rupture - Adipose tissue: systemic factor that accelerates cartilage rupture - Aging: - Changes in cells function → hinder tissue maintenance - Increase of the wear surface - Overuse: - Repetitive loads → deformity of the tissue - Cell death without regeneration TYPE OF INJURIES: - Chondropathy: - Etiology: overuse with minor repetitive trauma, sustained increase pressure of the cartilage or direct trauma - Interruption of nutrition from synovial fluid - Destruction - Osteochondritis: - Etiology: gradual wear aggravated by excessive loads, decrease of viscosity of the synovial fluid, or local cartilage injury. - Chondromalacia — fibrillation — subchondral bone exposure - Osteochondritis dissecans: - Etiology: degeneration of the central zone of the cartilage. - Proliferation of the perichondrium — peripheral ring of thickened cartilage – ossification – “Articular mice” 4. Hypothesis on biomechanics of cartilage degeneration PATELLAR CHONDROPATHY: Patella orientation and/or position is a determining factor in the genesis of inadequate cartilage compression - Static stabilizers: - Patellofemoral congruence - Medial and lateral retinacular - Patellofemoral ligaments - Patellar tendon - Dynamic stabilizers: - Quadriceps (specially → vastus mediallis) - “Goosefoot” - Femoral biceps IMBALANCE = INJURY ETIOPATHOGENIC FACTORS: - Abnormal patellofemoral morphology: - Patella dislocation during fetal life - No influence on external condyle → flat and small condyle  - Malalignment of extensor apparatus: - Defect of stabilizers: laxity of internal wing, hyperextension of external wing, angle Q greater than 20 or high patella - Defect of dynamic stabilizers: atrophy of the vastus medialis - Genu recurvatum or genu valgo - Femoral or tibial torsion. - Trauma: - Direct trauma: falls with patellar contact - Indirect trauma: flexion + external rotation → patella subluxation PATELLAR IMBALANCE — HYPEREXTENSION — SUBLUXATION — LUXATION — CHONDROMALACIA — OSTEOARTHRITIS 5. Functional tissue engineering of articular cartilage (no exam) CARTILAGE REGENERATION - Many possibilities of damage --> ¿REPAIR? - Based on the knowledge of the growth and maintenance of cartilage in a physiological form --> Development of strategies in the clinical setting for regeneration. - Three techniques: - Microfracture. - Autologous chondrocyte implantation (ACI). - Osteochondral auto- and allo-grafts. - Advantages and disadvantages --> ¿KEY POINTS? MICROFRACTURE: - Debridement of cartilage and drilling into the subchondral bone, together with a polymeric matrix of collagen, to obtain new fibrocartilaginous tissue. - PROS: - Single surgery. - If there is no bone loss, neocartilage is surrounded by native cartilage and doesn't support so much mechanical stress. - Initial significant improvement. - CONS: - Entire subchondral plate had to be removed. - Fibrocartilage doesn't support load bearing of the joint --> Mismatch between the native and neocartilage tissue. - Very long post-operatory treatment --> Load limited. - Lack of functionality at long-term AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI): - Two-stage process: 1. A biopsy of healthy cartilage is performed in an area of minimum load --> enzymatic digestion of the tissue and in vitro expansion of chondrocytes. 2. After 6 weeks - 18 months --> debridement and injection of the in vitro cell suspension with synthetic collagen.  - PROS: - Ensure restoration with only chondrocytes. - It is useful for patients for whom microfracture has not been successful. - CONS: - Very long process through two passes through the operating room - Very long post-operative treatment --> Load limited. OSTEOCHONDRAL AUTO-AND ALLO-GRAFTS: - Transplantation of full-thickness cartilage samples, including subchondral bone. - Biopsy in a minimum load area from the patient (auto-) or from a cadaveric donor (allo-). - The graft is implanted and fitted to align with the native cartilage. - PROS: - Short post-operative treatment --> Load limited during 6 weeks. - Good or excellent results in the long term. - CONS: - Allografts --> immunogenicity and disease transmission. - Autografts --> development of symptoms in donor area. NEW APPROACH: - Tissue engineering has emerged a few decades ago thanks to the transverse knowledge in: - Cell biology. - Biochemistry. - Materials science. - Engineering - MAIN CHALLENGE: develop functional tissue constructed in vitro that displays mechanical and biological characteristics, specially in terms of joint load. - MAIN PROBLEM: mimicking the developmental, mechanical, structural, and cellular changes that the original cartilage develops upon maturation in a very short time. CELL SOURCES AND CULTURE CONDITIONS: - The one that is either abundant or can be easily expanded in vitro, and which can produce large amounts of extracellular matrix components. - AUTOLOGOUS CHONDROCYTE CELL LINES: - Cell lines will never reflect all the phenotypic changes that would occur in vivo. - Cell lines will lead to the formation of tumors because of unlimited proliferation. - MESENCHYMAL STEM CELLS: - Their chondrogenic potential is very low. - The use of stem cells is promising but is still immature - CHONDROPROGENITOR CELLS: - It has been highlighted as an alternative to stem cells. - High chondrogenic potential. MATRICES FOR CARTILAGE TISSUE ENGINEERING: - Scaffolds must be made from a biodegradable and biocompatible material that is able to support and promote chondrogenesis. - Interconnected porous structure that allows cells to migrate and fluid to flow, and with mechanical properties to support joint load. - Two-strategies: - Scaffold must withstand the load in vitro and start to degrade, making space for the new tissue to grow. During the development of the new tissue in vivo, it still needs to be functional to support the applied load. - Scaffold will remain intact until the time of implantation with sufficient space for new tissue to grow. In vivo, the tissue remodels while sustaining most of the applied load as the scaffold degrades NATURAL POLYMERS AS SCAFFOLD MATRICES: - NATURAL POLYMERS: collagen, hyaluronan, agarose, alginate, chitosan, silk and other biopolymers. - Collagen I, II and III --> decellularization of a collagen matrix, retaining the tissue shape and extracellular matrix structure --> promoting chondrocyte proliferation and cartilage tissue formation. - Hyaluronan --> promoting the re-differentiation of encapsulated chondrocytes and high production of collagen. GOOD BIOCOMPATIBILITY AND CHONDROGENESIS BUT POOR FUNCTIONALITY SYNTHETIC POLYMERS AS SCAFFOLD MATRICES: - SYNTHETIC POLYMERS: polyesters, polyurethanes, polypropylene and polyphosphazenes. - PROS: ease of processing, preserving the sterility of the material, optimal mechanical properties, and the possibility of controlling the degradation times by altering their structure. - CONS: absence of an informational structure for cell attachment and their common hydrophobic character. GOOD MECHANICAL PROPERTIES BUT LACK OF BIOACTIVE MOLECULES CELL RESPONSE TO SCAFFOLD STRUCTURE: - HYDROGELS: - Rounded cells. - PROS: high water content and favours chondrogenesis. - CONS: low mechanical properties and formation of isotropic neocartilage. - FIBROUS: - Flattened cells. - PROS: formation of an interconnected porous structure. - CONS: formation of isotropic neocartilage, matrix characteristics of fibrocartilage, and difficult to produce 3D structures - FOAM OR SPONGES: - Tunable cells. - PROS: formation of defined structures and good mechanical properties. - CONS: formation of isotropic neocartilage, low water content and generally prepared with synthetic polymers. STRATIFICATION OF THE SCAFFOLD: - Native cartilage --> multi-layered material in which cell-shape, mechanical properties and matrix composition is different along the depth of the material. - STRATEGIES: - Bilayer system: chitosan-gelatin layer for cartilage and a hydroxyapatite-chitosan gelatin layer for subchondral bone. - Multi-phasic scaffold: bilayer chondrogenic part and a biphasic osteogenic part. - Sophisticated bilayer model: aligned fiber phase for cartilage regeneration and a porous isotropic phase for bone growth. - Multizonal scaffold: an anisotropic tubular top layer, a middle isotropic porous layer and a deep anisotropic tubular layer, oriented orthogonal to subchondral bone. FUTURE CHALLENGES: - Find the optimal scaffold: - - Biodegradable. - Mechanical integrity. - Ability to withstand the applied loads. - Adequate structure that guides the tissue formation to a mature hyaline-like structure. - Promote of the differentiation of cells to the chondrocytic phenotype. - Fin the optimal cell source: - Obtaining chondrogenic lineages with well-defined phenotypes Exercise to prevent cartilage damage - Physical exercise helps to lose weight, and improve the function of the muscle and ligaments, thus preventing wear of articular cartilage - Exercise promotes the growth of muscle fiber volume so help to discharge the joint - Physical activity regulates the load in the joint, helping to balance in the chondroblasts and chondrocytes function - Individualized evaluation of the etiopathogenic biomechanical factors - Generate variability in sports gestures to avoid overuse by repetition - Avoid impact gestures with high load until reaching a high level of physical conditioning Exercise training methods for osteoarthritis - JOINT ACTIVITY TRAINING: - Joint mobility → avoid stiffness - Activity mobility → alleviate tissue adhesion, improve blood circulation, accelerate metabolism, eliminate swelling and pain, and regulate chondrogenic function - AEROBIC EXERCISE: - Improve symptoms like swelling and limited mobility - Promote heart and lung function - It is unclear: swimming and cycling to avoid high joint loads; or running whose impacts promote the repair - AQUATIC EXERCISE THERAPY: - Promote blood circulation, relieve tissue adhesion and reduce the pressure on joints - Low water pressure can promote cartilage self-repair → more research is needed - MUSCLE STRENGTH TRAINING: - Multipoint intermittent isometric → muscle strength and function, without pain - Isotonic → not for acute inflammation phase