Anatomy: The Skeletal System

Skeletal System Overview

• The skeletal system consists of 206 bones in the human body, though this number varies with age due to fusion.
• It provides support, protects internal organs, assists in body movement, and produces red and white blood cells in the marrow.
• Mineral homeostasis occurs through calcium and phosphorus storage and release.

Bone Composition

• Bones are specialized, mineralized connective tissue, making up 18% of body mass with a density of 1.99 g/cm³.
• Types include long, short, flat, and irregular-shaped bones.
• Bone tissue includes both organic and mineral components.
• The organic component is a fibrous matrix mainly composed of 90% collagen type I.
• Crystalized mineral salts consist mostly of calcium phosphates and calcium carbonate.

Bone Tissue Classification

• Bone tissue exists in two forms: cortical and cancellous.
• Compact (cortical) bone forms the shaft and outer layer of all bones and has a dense structure of lamellae.
• Spongy (cancellous or trabecular) bone is located inside the ends of long bones and other bones.
• It is porous, made of trabeculae, lightens the bone, contains red marrow that produces blood cells, and houses blood vessels within its pores.

Red Bone Marrow

• Red bone marrow is vascularized connective tissue that contains a blood supply and supports other tissues.
• Found in spongy bone, such as the pelvic girdle and heads of the femur and humerus.
• Serves as the primary source of blood cells, where red and white blood cells and platelets are made.
• With increased age, red bone marrow turns into yellow bone marrow (fat cells).

Bone Cells

• Osteoblasts form the bone extracellular matrix (ECM).
• Osteocytes maintain bone tissue.
• Osteoclasts function in resorption and breakdown of the extracellular matrix (ECM).

Bone Remodelling

• Bone is constantly remodelled by two types of cells, osteoclasts (bone-resorbing) and osteoblasts (bone-forming).
• Osteoclasts break down old/damaged bone, reabsorbing calcium and phosphate.
• Remodelling occurs during growth to repair micro-damage and regain calcium availability.

Bone Dynamics

• Quiescence prevails when bone is at rest with osteocytes monitoring bone condition and sending signals to regulate remodeling.
• During resorption, osteoclasts break down old or damaged bone, secreting acid to break down minerals (calcium) and enzymes to break down the organic matrix (collagen).
• Reversal involves cleanup after osteoclasts, removing collagen and demineralized tissue to prepare osteoblasts to build new bone and coordinate between resorption and formation.
• Formation is where osteoblasts rebuild bone, laying down osteoid and trigger mineralization.
• Mineralization is when osteoid calcifies and hardens.
• The average skeleton is totally remodelled every 10–20 years, and an imbalance of this cycle leads to osteoporosis which leads to weak, brittle bones.
• Bone can normally heal itself, and treatments are used to ensure correct alignment during healing.
• Stress shielding happens when normal load transfers to an implant which is stiffer than the bone, but still allows bone to experience the increased load in order to regain strength.

Joints and Types

• Joints hold skeletal bones together while allowing for movement and flexibility.
• Three types of joints exist: fibrous, cartilaginous, and synovial.

Fibrous Joints

• Fibrous joints lack a synovial cavity and a fluid-filled space.
• Dense irregular connective tissue holds bones tightly together, allowing for little movement.
• These joints are strong, stable, and immobile.

Cartilaginous Joints

• Cartilaginous joints lack a synovial cavity.
• Bones are held together by cartilage, allowing for little movement.

Cartilage Properties

• Cartilage is avascular and consists of chondrocytes and ECM.
• Hyaline cartilage has a gel-like ground substance, fine collagen fibers, and many chondrocytes, providing a smooth surface for joint movement and reduces friction.
• Fibrocartilage has thick bundles of collagen fibers, scattered chondrocytes, and is stronger and more rigid than hyaline, withstanding compression and tension.

Synovial Joints

• Synovial joints allow joints to be freely movable, containing membranes that secrete synovial fluid.
• The synovial fluid is rich in hyaluronic acid and lubricin.
• There are six types based on movement: pivot, hinge, saddle, plane, condyloid, and ball and socket.

Osteoarthritis

• Osteoarthritis is a degenerative joint disease involving cartilage destruction, subchondral bone remodeling changes, and inflammation of the synovial membrane.

Total Joint Replacement (Arthroplasty)

• Artificial joints replace damaged or diseased joints where the lining cartilage is destroyed. Most joints can be replaced.

Biomechanics

• Biomechanics is the study of force relationships in different systems of the human body.
• Moments (torque) involve rotation around a specific point or axis, with M = Frsinθ.
• Moment arm represents the perpendicular distance from the line of force application to the axis of rotation, caused by muscle contractions about a joint.

Biomechanic Projects

• Identify the object as the "body".
• Identify all forces acting on the body.
• Draw an FBD & forces (FB, FA, FC, mg, FW)
• Select a point of rotation and write distances from rotation.
• Define the coordinate system and set up a static equilibrium equation.

Biomaterials

• Materials meant to interact with biological systems.
• Metals include stainless steel, cobalt, and titanium alloys.
• Ceramics include aluminum oxide, zirconia, and calcium phosphates.
• Polymers include synthetic materials like silicon or natural materials like collagen and gelatin.
• Biological materials consist of modified allogenic and xenogenic tissues.
• Composites feature a continuous phase and a discontinuous component.

Biomaterial Attributes

• Biocompatibility is noncarcinogenic, nonpyrogenic, nontoxic, nonallergenic, blood compatible, and non-inflammatory.
• Sterilizability is that it is not destroyed by typical sterilizing techniques, like autoclaving, dry heat, radiation, and ethylene oxide.
• Physical characteristics include strength, elasticity, and durability.
• Manufacturability should be machinable, moldable, and extrudable.
• Nothing is universally biocompatible, and the timeframe for compatibility should be considered.

Biocompatibility Paradigm

• Biomaterial and host come into contact.
• A host response starts causing a certain event to occur.
• Progression of the host response ensues.
• A resolution occurs depending on if it's a biocompatible or non-biocompatible system.

Material Properties

• Important factors include mechanical properties and surface chemistry.
• Mechanical properties include Elastic Deformation, Proportional Limit, Yield Strength, Breaking Strength, Ultimate Tensile Strength, Ductility, Hardness, Resilience, and Toughness.
• Elastic Deformation is shown by σ= Eε and τ=Gγ

Material Behaviour

• Initial Plastic Deformation causes polymer chains to start aligning.
• Chains continue stretching with little added stress.
• Chains are fully straightened, and even more stress is required to continue.
• Increasing temperature decreases stiffness and yield stress, which causes materials to behave in a more ductile manner.
• Decreasing temperature causes the opposite effect, and material is more brittle and stronger.
• Polymers are sensitive to small changes in temperature.
• Materials fail at lower stress due to preexisting microcracks or flaws.
• If applied stress > σc the crack will grow.

Cyclic Fatigue

• Fatigue Strength equals stress amplitude that causes failure after N cycles.
• Fatigue life quals # cycles required to cause failure at specific stress.

Viscoelasticity

• Viscoelasticity is how some materials behave like solids & liquids depending on how stress is applied over time.
• Stress relaxation is where stress needed to maintain the stretch decreases.
• Creep is when a constant load is applied to material, and material will keep stretching with no load Δ.

Surface Properties

• Surfaces have unique reactivity.
• Properties of a surface are not those of the bulk.
• Surface mass is very small, but has high impact.
• Surfaces contaminate easily.
• Surface molecules can move around.

Surface Energy

• Surface material behaves differently from bulk, creating excess energy (surface energy or surface tension).
• Atoms at the surface lack full bonding, which creates dangling bonds/unbalanced forces (surface tension).
• The system absorbs molecules to lower surface energy.

Surface Tension Influence

• Important property influences the biological response through protein absorption to materials, blood coagulation (thrombosis / clotting), and cell response to materials.
• Absorption is influenced by inter- and intramolecular forces, dependent on surface chemistry, and specific to hydrogen, ionic, Van der Waals, and hydrophobic interactions.

Surface Energy and Contact Angle

• The interactions determine protein absorption, blood coagulation/thrombosis (clotting), and cell response to materials.
• Absorption depends on intermolecular and intramolecular forces as well as the surface chemistry of the material, impacting H-bonds, ionic bonds, and hydrophobic and Van der Waals interactions.
• The contact angle between a droplet and a surface determines the spreadability and is defined using surface tensions and surface energy.
• In general low surface energy indicates a high water contact angle.

Wound Healing and Host Defence

• The body protects against pathogens, toxins, and abnormal cells to maintain homeostasis.
• Infection by pathogens can be bypassed with epithelial barriers and innate immune response.
• Wound healing involves changes in cells over time through hemostasis, inflammation, tissue formation and remodelling.

Layers of Host Defence

• Anatomical and physiological barriers.
• Innate immunity.
• Adaptive immunity.

Hemostasis and Inflammation

• Hemostasis stops blood loss from damaged vessels by vasoconstriction, platelet plug formation, and fibrin clot formation.
• Inflammation recognizes pathogens/injury through swelling, pain, redness, and heat, triggered by tissue damage and vasoactive signals in leaky capillaries.

Leukocytes and Chemotaxis

• Chemotaxis occurs when phagocytes are attracted to injury signals.
• Pathogen destruction happens as pathogens & immune cells kill bacteria & cleanup.
• Leukocytes are key to the immune system as they defend the body.
• Types include eosinophils, basophils, neutrophils, lymphocytes, and monocytes, with monocytes becoming macrophages.

Leukocyte Extravasation

• Extravasion involves rolling, activation, arrest/adhesion, and transendothelial migration, where leukocytes roll and bind to endothelial cells via selectins, are activated by chemokines, firmly stick to endothelium via integrins, and squeeze between endothelial cells for entry.
• E-selectin helps leukocytes find activated endothelial cells and binds to mucins.
• ICAM also helps with Leukocyte attachment to the endothelium

Complement System

• It consists of 20 plasma proteins, and functions in Cell lysis is a part of the innate immune response where complement proteins create pores to damage cell membranes.
• Opsonization tags pathogens for removal.

Inflammation in Tissue Repair

• Activation enhances inflammation, creating the desire response.
• Re-epithelialization occurs during inflammation and granulation to restore the skin barrier and homeostasis.

Granulation for Tissue Formation

• Macrophages release cytokines and growth factors, recruiting fibroblasts and endothelial cells to promote a collagen-rich matrix (replaces provisional matrix)
• Endothelial cells trigger angiogenesis (growth of new vessels) that brings oxygen and nutrients for tissue growth.
• When wound starts building new tissue Angiogenesis process

Wound Remodeling and Host Response

• Angiogenesis: blood starved cells release angiogenic cytokines to grow and sprout towards the area led by a special “tip cell".
• Sprouts meet & form a capillary tube that fills with blood so smooth muscle cells are recruited, and heal tissue.
• Granulation tissue is replaced to create stronger/permanent tissue over time, where fibroblasts become myofibroblasts, contracting the wound and reorganizing collagen for max strength.

Foreign Body Reaction and Biomaterials

• Bodies respond to implanted materials such as proteins, cells a tissue level.
• Start with a normal inflammatory response, if the inflammation is not remodeled, it leads to a chronic inflammatory state.
• A fibrous capsule forms around implant, and can cause issues with new material.
• The response includes protein absorption, provisional matrix formation, complement activation, macrophage, and a fibrous formation.
• Blood material interactions is made up of both protein absorption, coagulation, and the activation of the immunce system

Vroman Effect and Competitive Displacement

• First, small proteins quickly adsorb because of concentration gradients.
• Over time larger ones displace the small ones

Frustrated Phagocytosis & Macrophage Fusion

• Activated macrophages try to digest and fuse causing cell damage
• In the process the activated Macrophages are fused together to form FBGC which secret degradative mediators and damage nearby substance by the acids

Resolution of FBR Process

• Extrusion: The body pushes the materiel out. Usually the splinter.
• Resorption: Material is broken down and absorbed by the body
• Encapsulation: body walls it off with collagen rich fibria
• Integration: Material stays and merges with the body