Biomechanics of Muscle PDF

BOĞAZİÇİ UNIVERSITY Biomedical Engineering Institute BIOMECHANICS LABORATORY BM 525 TISSUE BIOMECHANICS INTRODUCTION TO BIOMECHANICS (I) DEFINITIONS FOR BIOMECHANICS...

BOĞAZİÇİ UNIVERSITY Biomedical Engineering Institute BIOMECHANICS LABORATORY BM 525 TISSUE BIOMECHANICS INTRODUCTION TO BIOMECHANICS (I) DEFINITIONS FOR BIOMECHANICS What is biomechanics? What is mechanics? Mechanics is the study of motion (or in a special case, the equilibrium) of matter and the forces that cause such motion and is based on concepts of time, space, force, energy and matter Galileo used the word mechanics in 1638 as a subtitle to his book Two New Sciences in order to describe force, motion and strength of materials Mechanics is related closely to mathematics: the main aim is the formulation of physical problems in mathematical form What is biomechanics? Biomechanics is discipline of science that is relatively newly developed and established Various definitions for biomechanics are proposed, some being broad, some rather limited What is biomechanics? Biomechanics is a contraction of the words ‘biology’ and ‘mechanics’. What is biomechanics? Biomechanics is a contraction of the words ‘biology’ and ‘mechanics’. Biomechanics is mechanics applied to biology What is biomechanics? Biomechanics is a contraction of the words ‘biology’ and ‘mechanics’. Biomechanics is mechanics applied to biology Biomechanics is the science that examines forces acting upon and within a biological structure and effects produced by such forces What is biomechanics? Effects of forces are Motion for any mechanical for a biological Deformation structure structure Biological changes in the tissue What is biomechanics? Therefore, biomechanical research studies Motion of different body segments and factors that affect the motion Deformation of biological structures Biological effects of locally acting forces on living tissue including growth and development, adaptation or overload and injuries (III) Fiber direction strain fiber direction proximal distal -.31 -.22 -.13 -.04.06.15.24.33.42.52 DIVISIONS OF BIOMECHANICS Divisions of Biomechanics Traditionally, the field of biomechanics can be divided in to three parts (1) Tissue biomechanics (2) Motion biomechanics (3) Fluid biomechanics (1) Tissue biomechanics It deals with the mechanical behavior of various tissues in the human (and animal) body, ranging from cell level to organs The tissue deformations under mechanical loading are studied, with the accompanying strains and stresses in the material It is e.g. attempted to predict the physiological function and what the failure criteria and failure mechanisms are, but also how the tissue may adapt to the loading proximal EHL distal EDL (2) Motion biomechanics The motions of the structures of the neuromusculoskeletal system are analyzed The focus is on the role of muscles, bones, joints, sensors as well as the central and peripheral nervous system (3) Fluid biomechanics Mechanics of all biological fluids are studied However, the focus is on the cardiovascular system, the way blood is transported through the vessels, and the effort of the heart to pump the blood around in the body (VI) INTRODUCTION TO THE MUSCULOSKELETAL SYSTEM Musculoskeletal system Bone Cartilage Ligament Tendon Muscle Bone l Bone is the hard tissue that is the main structural component of the skeleton l It is stiff, strong, tough and resilient l Its primary function is load carrying, compressive loads in particular Bone l Composed of about 30% organic material (predominantly collagen fibers embedded in a matrix) 60% inorganic material A look ahead (mainly hydroxiapatite crystals) a mineral containing Collagen is a fibrous calcium and phosphorus protetin It is the major 10% water structural element of soft and hard tissues in animals Bone l Bone is a composite material which has greater strength than either of its components The mineral content provides the stiffness The fibrous content produces the toughness l Bone is an inhomogeneous material Its mechanical properties depend not only on its composition but also on its distribution l Bone is an anisotropic material Its mechanical properties are different in different directions Bone l Bone is a viscoelastic material Its mechanical properties are time dependent l Bone is a dynamic, adaptive material The mechanical properties of bone are highly dependent on the condition of the bone Age, gender and the health of an individual affect such properties Bone Two types of tissues that comprise bone are distinguished Cortical bone is the dense outer layer of a bone Cortical bone Bone Two types of tissues that comprise bone are distinguished Cortical bone is the dense outer layer of a bone Cancellous bone is the porous spongy bone found inside the shell of compact cortical bone Cancellous bone Cartilage l Cartilage is a specialized connective tissue with a high collagen content, but no mineral content A look ahead Connective tissue is a tissue that is rich in extracellular matrix (collagen, proteoglycan etc.) and that surrounds other more highly ordered tissues and organs Bone and cartilage are known as specialized connective tissue Cartilage l Articular cartilage is a significant component of the musculoskeletal system with a major functional role in motion l It plays a major role in the movement of one bone against another It has an incredibly low coefficient of friction It can bear very large compressive loads Cartilage l Articular cartilage has inhomogeneous, viscoelastic and anisotropic mechanical properties l The mechanical properties are related to the orientation of the collagen fibers l It contains no blood vessels so it has a limited healing capacity Ligament l Ligament is a fibrous band of soft tissue joining two bones of a joint. l The biomechanical functions of ligaments are (1) To resist external load (2) To guide relative movements of the two bones (3) To control the maximum range of joint motion Tendon l Tendon is a strong fibrous cord of soft tissue by which muscle is attached to bone l The biomechanical functions of tendon are (1) To transmit muscle force to bone (2) To store elastic energy l Tendon contains blood vessels and it is able to heal after injury Tendon l The internal portion of the tendon is called an aponeurosis tibia EHL proximal distal EDL distal EDL aponeurosis proximal tendon distal tendon of EDL of EDL Muscle l Muscle is an activatable soft tissue l Its function is to generate and exert force Þ produce movement l When stimulated by a nerve muscle shortens if it can overcome the external resistance imposed on it l Shortening and force production of muscle is referred to as contraction Skeletal muscle Structure l Like all tissues, skeletal muscle is composed of - cells Þ intracellular space - the structure outside the cells Þ extracellular space l The activatable single cells of muscle tissue are the muscle fibers Skeletal muscle Intracellular space Þ Active mechanical properties Extracellular space Þ Passive mechanical properties l Anisotropic l Non-linear l Viscoelastic l Constant volume  BOĞAZİÇİ UNIVERSITY Biomedical Engineering Institute BIOMECHANICS LABORATORY BM 525 TISSUE BIOMECHANICS BIOMECHANICS OF MUSCLE (I) HISTORICAL HIGHLIGHTS Selected historical highlights 384 – 322 B.C. Aristotle The origins of discovery of muscles as the organ of force and movement production may be found in ancient Greece 129 – 201 Galen The discovery that muscles are the true organs of voluntary movements must be accreditted to Galen Selected historical highlights 1543 Vesalius He discovered that the contractile power resides in the actual muscle substance, and he identified individual structural components of muscles 1663 Swammerdam He showed the constancy of muscular volume during contractions by experiments on frog and human muscles Selected historical highlights 1663 Stensen Gave precise descriptions of muscular structures, showed that muscle fibers connect to tendons and stated that contractions may occur without changes in muscular volume 1682 van Leeuwanhoek He parformed examinations with light microscope and discovered the cross-striation of skeletal muscles Selected historical highlights 1939 Engelhardt With the use of electron microscopes researchers in muscle biochemmistry were able to associate actin and myosin proteins with the thin and thick myofillaments and discover the activity of myosin 1954 Huxley A.F. and Huxley H.E. Proposed the the theory of sliding fillaments (A.F. Huxley and Niedergerke, 1954; H.E. Huxley and Hanson, 1954) and finally the Cross-bridge Theory (A.F. Huxley, 1957). The cross-bridge theory has become the accepted paradigm for muscular force production (II) MORPHOLOGY Skeletal muscle Structure l Like all tissues, skeletal muscle is composed of - cells Þ intracellular space - the structure outside the cells Þ extracellular space l The activatable single cells of muscle tissue are the muscle fibers Structural units: epimysium The entire muscle is typically surrounded by a fascia and a further connective tissue known as the epimysium epimysium The epimysium consists of irregularly distributed collagen fibers, connective tissue cells and fat Structural units: fascicle The next smaller structure is a fascicle which is a muscle bundle that consists of a number of muscle fibers fascicle Structural units: perimysium Each fascicle is surrounded by a connective tissue structure called perimysium perimysium Structural units: muscle fibers Then comes the muscle fiber, an individual muscle cell muscle fiber Structural units: sarcolemma The muscle cells (fibers) are within a cell membrane called the sarcolemma sarcolemma Structural units: endomysium Each muscle cell is surrounded by the endomysium, a thin sheet of connective tissue endomysium endomysial tunnels Muscle can be represented as an extensive 3D set of endomysial tunnels within which the muscle fibers operate Structural units: myofibrils Muscle fibers are made up of myofibrils lying parallel to one another. myofibril The systematic arrangement of myofibrils gives skeletal muscle its typical striated pattern Structural units: sarcomere The basic contractile unit of a muscle is a sarcomere and it is the repeat unit in the striated pattern sarcomere Structural units: myofilaments Sarcomeres are comprised of thin (actin) and thick (myosin) myofilaments myofilaments Muscle fibers Þ muscle cells When an individual muscle fiber is isolated, it has a characteristic banded or striated appearance under the light microscope The banded structure persists down to the level of single myofibrils sarcomere myofibril These striated bands divide the muscle fiber up into sarcomeres, the smallest functional unit which still behaves like a muscle Thick filament: myosin molecule A myosin molecule contains a long tail portion, known as the light meromyosin a globular head attached to the tail, which is called the heavy meromyosin globular head tail portion Thick filament: cross-bridges The head portion extends outward from the thick filament It contains a binding site for actin and an enzymatic site that catalyses the hydrolysis of ATP that releases the energy needed for muscular contraction The myosin heads have the ability to establish a link between the thick and thin filaments, they are called as cross-bridges Thick filament: cross-bridges The cross-bridges on the thick filament are 14.3 nm apart in the longitudinal direction and 60° off set to one another They are believed to come in pairs offset by 180° Therefore, two cross-bridges with identical orientation are believed to be approximately 43 nm apart (~ 3x14.3 nm) Thin filament: actin molecule actin molecule myosin binding site The major part of the thin filament is composed of two chains of serially linked actin molecules The diameter of each actin molecule is about 5-6 nm The strands of serially linked molecules cross over one another every 5 to 8 units in a somewhat random manner Thin filament: troponin and tropomyosin troponin tropomyosin Thin fillaments further contain tropomyosin and troponin Tropomyosin is a long fibrous protein that lies in the groove formed by the actin chains Troponin molecules are located at intervals of 38.5 nm along the thin filament Thin filament: troponin and tropomyosin troponin troponin Troponin is composed of three subunits: complex Troponin C, which contains sites for calcium ion (Ca2+) binding Troponin T, which contacts tropomyosin Troponin I, which blocks the cross-bridge attachment site in the resting state Titin filaments Titin is a huge protein which spans from the Z-disc to the M-line within the sarcomere It is the main mechanical element of intracellular cytoskeleton i.e., it acts like a spring titin (III) SLIDING FILAMENT THEORY Sliding filament theory What happens during contraction is that the myosin heads are "walking" up the actin filaments, pulling them closer together In contrast to the earlier beliefs, the myosin and actin filaments are not made shorter during contraction of the muscle fiber Instead, they slide relative to each other which makes the sarcomere shorter, but the length of the filaments themselves remain unchanged Sliding filament theory: Huxley models In 1954, Hugh E. Huxley wrote a paper with Jean Hanson suggesting a model for the configuration of muscle proteins In the same year, a manuscript prepared by Andrew F. Huxley and R. Niedergerke proposed the identical model The two papers were published back-to-back in the same issue of Nature (Volume 173, pp. 973-76 and pp. 971-73, respectively) Sliding filament theory: Huxley models It was proposed that when the muscle shortens or lengthens, these two types of filaments slide pass one another Sliding filament theory The sliding of the filaments is dependent on the cross-bridging of myosin heads to actin filaments Therefore, force of the contraction is proportional to the degree of overlap between actin and myosin filaments actin myosin Sliding filament theory The force developed is dependent upon the number of cross bridges that can be formed After lengthening where there is no overlap, the sarcomere cannot develop any tension when stimulated In the other extreme, after shortening the myosin filament crumble up against the Z-discs, the myosin heads become out of alignment and, therefore, prevented from forming cross bridges Cross-bridge cycle (IV) FORCE PRODUCTION IN THE SARCOMERE LEVEL The development of sarcomere force is determined by (i) the length of the sarcomere Þ length-force relationship (ii) its time rate of shortening Þ force-velocity relationship Isometric conditions The length-force relationship is determined by the isometric activity of a sarcomere This means that both ends of a sarcomere are fixed (one end is connected to the mechanical ground and the other is attached to a fixed force transducer) Þ the length of the sarcomere is not altered during the contraction This is repeated at different sarcomere lengths and the collection of the data shows the length-force relationship Isometric conditions: optimum sarcomere length lthin lz lfree Optimum sarcomere length (lsao) refers to the optimal (full) overlap between the filaments lsao = lz + 2 x lthin + lfree Isometric conditions: sarcomere l-f relationship If an active sarcomere is lengthened above the optimum length the number of cross-bridges will reduce and so will the force This reduction occurs in a linear fashion as a 100 Force (% of maximum) function of sarcomere 80 length 60 40 20 The force reduces to 0 1.0 1.5 2.0 2.5 3.0 3.5 4.0 zero if there remains Sarcomere length (μm) no overlap between the myofilaments Isometric conditions: sarcomere l-f relationship Also if an active sarcomere is shortened below the optimum length the force will again reduce This reduction does not occur in a linear 100 Force (% of maximum) fashion 80 60 The force reduces 40 20 to zero at very low 0 sarcomere lengths 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Sarcomere length (μm) the myosin filament contacts the Z-discs Dynamic conditions The force-velocity relationship is determined by the isokinetic activity of a sarcomere This means that one end of a sarcomere is fixed (connected to the mechanical ground) and the other end is attached to a force transducer which is allowed to move at a constant speed This is repeated at different speeds and the collection of the data shows the force-velocity relationship Dynamic conditions: sarcomere f-v relationship Under dynamic conditions the force is measured when the shorthening muscle passes from a length of interest at different velocities lsa o Fsa (nN) 300 240 0.82 lsa o 180 0.70 lsa o 120 0.60 lsa o 60 0 10 20 30 40 50 Vsa (μm/s) At lengths lower than the optimum length, the forces measured are lower Dynamic conditions: sarcomere f-v relationship Note that vsa = 0 is the isometric condition lsa o Fsa (nN) 300 240 0.82 lsa o 180 0.70 lsa o 120 0.60 lsa o 60 0 10 20 30 40 50 Vsa (μm/s) Also the forces at each length are lower under dynamic conditions than when they are measured isometrically Dynamic conditions: sarcomere f-v relationship The velocity at which the force attains a value of zero is referred to as maximal velocity of contraction lsa o Fsa (nN) 300 240 0.82 lsa o 180 0.70 lsa o 120 0.60 lsa o Vsa max 60 0 10 20 30 40 50 Vsa (μm/s) Vsamax is calculated as 20 x the optimum length of the sarcomere / second Dynamic conditions: sarcomere f-v relationship Fundamental property of sarcomeres: Force production and velocity of shortening are not interchangeable properties lsa o Fsa (%) 100 80 At maximal velocity, 0.82 lsa o the force is zero and 60 0.70 lsa o a maximal force can 40 0.60 lsa o only be produced Vsa max 20 when the velocity is zero (isometric) 0 20 40 60 80 100 Vsa (%) (V) HILL’S MUSCLE MODEL CE PEE SEE Hill’s model Hill’s model t represents an active muscle as composed of three elements Contractile element Parallel elastic element Series elastic element t Hill’s model: contractile element Contractile element is commonly identified with the sliding- filament theory and the generation of active tension with the number of active cross-bridges between actin and myosin myofilaments at rest it is freely extensible (i.e., it has zero tension) CE when activated it is capable of shortening PEE but not capable of instantaneous SEE length change Hill’s model: series elastic element The series elasticity may be due to the intrinsic elasticity of the actin and myosin molecules and cross-bridges that of the Z-discs non-uniformity of the sarcomeres and CE non-uniform activation of the myofibrils PEE SEE Hill’s model: parallel elastic element The parallel elasticity may be due to intramuscular connective tissues cell membranes, collageneous sheets CE PEE SEE Notes on Hill’s model: limitation A muscle is regarded as an accumulation of sarcomeres However, the assumption that all sarcomeres have identical lengths is not representative CE PEE shortened sarcomeres SEE lengthened sarcomeres -.14 -.07.01.08.15.22.29.37.44.51 (VI) 100 LENGTH-FORCE RELATIONSHIP 80 OF SKELETAL MUSCLE 60 F (%) 40 GM 20 EDL 0 40 60 80 100 120 140 160 lf (%) Muscle length-force characteristics When a muscle is tetanized, the force exerted is greater than it was when the muscle is relaxed Isometric experiments performed on tetanized muscle at several muscle lengths yield muscle length-total force characteristics Force total force Length Muscle length-force characteristics Isometric experiments performed on passive muscle at several muscle lengths yield muscle length-passive force characteristics Force total force passive force Length Muscle length-force characteristics Commonly the isometric muscle length-passive force data is subtracted from the muscle length-total force data to obtain the muscle length-active force characteristics ls : muscle active Force slack length active force lo : muscle optimum length ls lo active length range Length of force exertion Muscle length-force characteristics Different muscles show different length-force characteristics Force Force gastrocnemius sartorius Length Length Muscle length-force characteristics Normalized force and length to their optimum may show similarities among length-force characteristics of different muscles 100 80 60 F (%) 40 GM 20 EDL Fiber bundle length- 0 force relationship for rat 40 60 80 100 120 140 160 gastrocnemius (GM) lf (%) and extensor digitorium longus (EDL) muscles Zuurbier et al., 1995 BM 402 / Engineering in Medicine Topic: Biomaterials in Medicine Fall Semester 2024/2025 Instructor: Dr. Banu İyisan https://bindlab.bogazici.edu.tr/ 1  Biomaterials A biomaterial is a nonviable material used in a medical device, intended to interact with biological systems - WILLIAMS (1987) 2  Biomaterials If the word “nonviable” is removed, the definition becomes even more general, and can address many new tissue-engineering and hybrid artificial organ applications where living cells are used. A material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body. Williams, D.F.: Williams dictionary of biomaterials, Liverpool University Press (1999) 3 Biocompatibility Biocompatibility is the ability of a material to perform with an appropriate host response in a specific application (Williams, 1987) Williams, D. F. (1987). Definitions in Biomaterials. Proceedings of a Consensus Conference of the European Society for Biomaterials, Chester, England, March 3–5, 1986, Vol. 4, Elsevier, New York. 4 Other Important Definitions Biological Response: host response towards a material Biodegradation: breakdown of a material in a biological system Bioactive material: A biomaterial intended to cause or modulate a biological activity Bioactivity: Degree of wanted (positive) reaction from tissues 5 Classes of Biomaterials A. Basic Types of Materials: 1. Polymers 2. Metals 3. Ceramics B. Combination of Basic Types of Materials 4. Composite Materials Classification is based C. Nanomaterials primarily on their chemical Nanoscale form of Basic characteristics, atomic structures and properties. Materials D. Natural Materials Naturally occurring form of Basic Materials 6 Basic Types of Biomaterials 7 Biomaterials are used in: Hearth Valve A hip prosthesis Joint replacements Bone plates Bone cement Artificial ligaments and tendons Dental implants for tooth fixation Blood vessel prostheses Heart valves Skin repair devices (artificial tissue) Cochlear replacements Contact lenses Breast implants 8 The human impact, and the size of the commercial market for biomaterials and the broad array of medical devices, is impressive 9 10 11 12 The path from the basic science of biomaterials, to a medical device, to clinical application. 13 Biomaterials Challenges Toxicology Biocompatibility Inflammation and Healing Anatomic location Mechanical performance requirements (basic materials science and engineering) Industrial involvement (commercial, balance of patient needs and company needs) Ethics (animals, human subjects) Regulatory Agencies Interdisciplinary nature 14 History Biomaterials 15 Significant Developments in the history of biomaterials 16 History Biomaterials 17 1. POLYMERS Polymers are organic materials consisting of long-chain molecules composed of many small repeating units (called ‘mers’). Organic compounds of carbon, hydrogen, and other nonmetallic elements (i.e., O, N, and Cl,…). They have very large molecular chain structures having carbon as back-bone element. Examples: Synthetic: Polyethylene glycol (PEG), polyvinyl chloride (PVC), polycarbonate (PC), polystyrene (PS), Natural: Collagen, Cellulose, DNA Common properties: Low density, Neither stiff nor strong compared with other material types, Many of them are very ductile (i.e., plastics), which means they are easily formed into complex shapes. Corrosion resistant, They are soften, sometimes burned at high temperatures, Low electrical conductivity and nonmagnetic. POLYETHYLENE Molecule (mer) 3D Model Carbon (C) is backbone element and Hydrogen (H) is attached to C by covalent bonding in each molecule. The covalent bonds in each molecule are strong, but only weak hydrogen and secondary (weak) Van der Waals bonds exist between the molecules.  Polymers in Specific Biomedical Applications Application Properties and design requirements Polymers used dental stability and corrosion resistance, PMMA-based resins for plasticity fillings/prosthesis strength and fatigue resistance, coating polyamides activity poly(Zn acrylates) good adhesion/integration with tissue low allergenicity ophthalmic gel or film forming ability, hydrophilicity polyacrylamide gels oxygen permeability PHEMA and copolymers orthopedic strength and resistance to mechanical PE, PMMA restraints and fatigue PL, PG, PLG good integration with bones and muscles cardiovascular fatigue resistance, lubricity, sterilizability silicones, Teflon, lack of thrombus, emboli formation poly(urethanes), PEO lack of chronic inflammatory response drug delivery appropriate drug release profile PLGA, EVA, silicones, compatibility with drug, biodegradability HEMA, PCPP-SA sutures good tensile strength, strength retention silk, catgut, PLG, PTMC-G flexibility, knot retention, low tissue drag PP, nylon,PB-TE Classifications of Polymers by Origin Natural Synthetic Protein Polyesters Polysaccharides Polystyrene Nucleic Acids PMMA Natural Rubber Polyurethane Lignin PEG Natural polymers are occuring in plants and animals whereas synthetic ones are hand-made materials!! 21  Synthetic Polymers Advantage: Ease of manufacturability, process ability and reasonable cost Required properties Biocompatibility Sterilizability Physical property Chemical property Applications: Medical disposable supplies, prosthetic materials, dental implants, dressings, polymeric drug delivery, tissue engineering  Natural Polymers In general, these can be categorized into three types of biopolymers: (1) proteins–chains of amino acids (e.g., collagen, elastin); (2) polysaccharides–chains of sugar (e.g., chitosan, chitin, cellulose, glycosaminoglycans); (3) nucleic acids–chains of nucleotides (DNA, RNA) 27 Advantages: They might be derived from plants, animals (xenogenic), or humans (allogenic and autologous). Natural polymers offer several advantages with respect to synthetic polymers. 1) they frequently avoid the immunogenic response and toxicity typical of synthetic polymers, thus presenting higher biocompatibility; 2) (they contain bioactive motifs enabling local remodeling and cell spreading and a fibrillar architecture that can be deformed by cells, thus better mimicking the extracellular matrix (ECM); and 3) they can be recognized and metabolically processed by the body. Disadvantages: However, natural polymers have historically been associated with some disadvantages, including 1) batch-to-batch variability, 2) lower modularity, and 3) inadequate biomechanical properties. Recent developments in the field have led to a reduction in these drawbacks, and allowed exploration of the full potential of naturally occurring polymers to develop a number of biomaterials that mimic key aspects of the native ECM 28  Proteins are polyamides The monomers are amino acids: React via condensation polymerization  Hydrogels Hydrogels are a class of polymeric materials with a three‐dimensional (3D) structure. Due to their high water content and their good biocompatibility, they have many biomedical applications. Their use in tissue engineering as porous scaffolds for repairing and regenerating a wide variety of tissues and organs are promising because hydrogels are are structurally similar to the natural extracellular matrix (ECM) of many tissues Tissue engineering aims to replace, repair, or regenerate tissue or organ function and to create artificial tissues and organs for transplantation. Hydrogels are composed of hydrophilic polymer networks (synthetic, natural, or mixed), which can swell in water. The molecular construction of a hydrogel network is held together by physical interactions like hydrophobic forces, hydrogen bonds, chain entanglement, crystallinity, electrostatic interactions, or specific interactions, that is, antibody– antigen, avidin–biotin, or carbohydrates– lectins. Physical gels can undergo disintegration in the proper conditions. The so‐called chemical gels are composed of polymer Bio- and Multifunctional Polymer architectures, B. Voit, R. Haag, molecules that have been cross‐linked by D. Appelhans, P. B. Welzel, John Wiley & Sons, 2016. (chapter 3) covalent bonds. 30 A variety of synthetic and naturally derived materials may be used to form hydrogels. Synthetic materials include =>poly(hydroxyethyl methacrylate) (PHEMA), poly(ethylene oxide) (PEO), poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), poly(acrylic acid) (PAA), poly(methyl methacrylate) (PMMA), poly(acrylamide) (PAAm), poly(vinylpyrrolidone) (PVP), and poly(N‐isopropylacrylamide) (PNIPAAm) and its derivatives. Representative natural materials used for hydrogel fabrication are =>fibrin, gelatin, collagen, cellulose, agarose, alginate, dextran, chitosan, and HA Moreover, by combining naturally derived polymers with synthetic building blocks, hybrid materials can be created offering both a defined functionality and biocompatibility as well as a high adaptability in terms of composition and structure. => In the production of such hybrid systems, PEG is one of the most commonly used synthetic components since it provides excellent biocompatibility, a hydrophilic and uncharged character, and the possibility to easily modify its terminal end groups. 31 Stimuli‐responsive hydrogels are polymer networks that sense and respond to changes in their external environment. They can undergo dramatic changes in swelling, network structure, permeability, and mechanical strength due to external stimuli, such as changes in  pH,  ionic strength,  electrical or magnetic fields,  temperature, and  changes in the concentration of biologically active molecules, like glucose or enzymes 32 Hydrogel scaffolds have many different functions in the field of tissue engineering. They are applied as  space filling agents.  Bioactive molecules are delivered from hydrogel scaffolds in a variety of applications including promotion of angiogenesis and encapsulation of secretory cells.  Hydrogel scaffolds act as 3D support structures for cell growth and function. Examples of uses in Tissue Engineering - alginate mixed with chondrocytes and scaffolds made from PVA have been used for cartilage replacement. Dextran/laminin and gelatin/laminin scaffolds were tested for neural tissue regeneration Due to their elastic properties, PVA hydrogels were also investigated for the reconstitution of vocal cords 33 2. METALS Composed of one or more metallic elements (e.g., iron, aluminum, copper, titanium, gold, and nickel), and sometimes also nonmetallic elements like carbon, nitrogen, and oxygen in small amounts. Distinctive characteristics: Atoms are arranged orderly in the space, Relatively denser than ceramics and polymers, Stiff, strong and ductile, Strong: High load carrying capacity, Ductile: Capability of large deformations before fracture) Good conduction of electricity and heat, Non-transparency Some of them (i.e., Fe, Co, and Ni) have desirable magnetic properties. Disadvantages : Possibility of corrosion METALS Metals as Biomaterials Screws and plates 3.5mm Titanium Plate along with 3.5mm Self Tapping Titanium Screws  Corrosion of Metallic Implants Corrosion is the unwanted chemical reaction of a metal with its environment, resulting in its continued degradation to oxides, hydroxides, or other compounds. Corrosion of Metallic Implants The human body presents a very aggressive environment for metals used for implantation. Corrosion resistance of a metallic implant material is consequently an important aspect of its biocompatibility. Corrosion of Metallic Implants Because different parts of the body have different pH values and oxygen concentrations a metal that performs well in one part of the body may suffer an unacceptable amount of corrosion in another part.  Engineering Alloys A. Ferrous (Fe Based) Alloys B. Non Ferrous Alloys I. Steels II. Cast Irons Copper Alloys Constructional Steels White Cast Iron Aluminum Alloys Plain C Steels Gray Cast Iron Magnesium Alloys Titanium Alloys Low Alloy Steels Malleable Cast Iron Refractory Metals High Alloy Steels Ductile Cast Iron Superalloys Tool Steels Austenitic SS Stainless Steels Ferritic SS Martensitic SS The major alloys in use today consist of metals intended - for indefinite use within the body : permanently implantable alloys / the principal ones applied to a wide range of medical devices currently in use today - and those that are designed to be temporary, ultimately degrading or biocorroding over time : biodegradable alloys are in development or used in a small set of approved applications. 41 The three major permanently implantable alloy systems used in the body across the spectrum of medical devices are: (1) stainless steels (primarily 316L stainless steel [ASTM F-138]), (2) cobalt–chromium–molybdenum (CoCrMo [ASTM F-75; ASTM F-799; ASTM F1537]) alloys, and (3) titanium (ASTM-F76) and its alloys (ASTM F136). Other permanently implantable alloys include Pt, Au (ASTM-F72), and Ag alloys. ASTM : American Society for Testing and Material 42 43 The big three—stainless steel, CoCrMo, and Ti–have a number of alloy systems that have seen widespread adoption for applications within the body. Stainless steels (primarily 316LVM stainless steel [ASTM F-138]) are used in surgical instrumentation, but also, importantly, in many medical devices, including screws, rods, and plates for bone fixation and in spinal fusion devices. Cobalt–chromium–molybdenum alloys (ASTM F-75; F-799; F-1537) are typically used in applications where high strength, fatigue resistance, and wear resistance are needed. CoCrMo is one of the most wear resistant alloys known and has been used for decades in total joint applications. Titanium and its principal alloy (Ti-6Al- 4V) are used in dental implants as well as total joint replacements among other applications (ASTM F-67; ASTM F-136). This alloy has high strength, low modulus, and is particularly good at interfacing with the biological system. Bone ingrowth into porous titanium surfaces, known as biological fixation, is a primary means by which orthopedic implants affix to bone directly. 44 For degradable alloys, the primary interest is to find alloys that will remain capable of carrying the applied loads and wear processes until the body has healed sufficiently that they are no longer required, and will then corrode away and be resorbed and eliminated by the body. Magnesium alloys have been investigated the most. This alloy is known to corrode rapidly in physiological solutions and that the oxidation products are mostly Mg oxide (MgO or Mg(OH)2), which is relatively innocuous, and hydrogen gas, which can be problematic. Other alloy systems, including Sn, Fe, and Zn, are under consideration as degradable alloys for biomaterials applications as well. 45 3. CERAMICS Compounds of metallic and nonmetallic elements. They are most frequently in the forms of oxides, nitrides, and carbides (e.g. aluminum oxide Al2O3 (alumina), silicon dioxide SiO2 (silica), silicon carbide SiC, silicon nitride (Si3N4) and other traditional ceramics like clay minerals, cement and glass. Common properties: Stiff and strong, Very hard but with loss of ductility (i.e. brittle), highly susceptible to fracture, They are more resistant to high temperatures, some of them are used for cookware and even automobile engine parts. Poor heat and electricity conduction (i.e. good insulators), Some of them are transparent, Corrosion resistant… Clinical application of ceramic biomaterials Venina dos Santos, Rosmary Nichele Brandalise, and Michele Savaris, Ceramic Biomaterials.Engineering of Biomaterials pp 29-38. General Classification of Ceramics A. Crystalline Ceramics (Crystal Structured) 1. Traditional Ceramics 2. Advanced (Engineering) Ceramics B. Glasses (Amorphous Structured) 1. Soda-Lime Glass 2. Lead Glass 3. Borosilicate Glass 48 A. Crystalline Ceramics 49 What are bioceramics? Bioceramics can be defined as ceramic materials which are biocompatible. https://fci-ophthalmics.com/products/spher-egg-shaped-bioceramic-orbital-implants 50 What are bioceramics? Ceramic, glass, and glass-ceramic implant materials can be broadly grouped as bioceramics. ▪ are generally used to repair, replace, or regenerate bone or teeth, and their applications are becoming broader with time ▪ can be used as coatings to improve the biocompatibility of metal implants ▪ can function as resorbable lattices which provide temporary structures and a framework that is dissolved 51 Classifications of Bioceramics 52  Classification of Bioceramics based on implant – tissue interactions Bioinert Ceramics Little or no physiological reaction in the human body Example: Alumina, orthopaedic implant Bioactive Ceramics React in a positive way with local cells Directly attach by chemical bonds and have a substantially higher level of reactivity Example: Bioglass Resorbable Ceramics Porous or nonporous structures which are slowly and gradually replaced by bone Example: Tricalcium phosphate, bone void fillers 53 4. COMPOSITES Composed two (or more) types of basic materials. The aim is to achieve a combination of good properties that is not displayed by any single type of material. Best example is glass fiber reinforced plastics (GFRP). Fine glass fibers are embedded in a polymer matrix (epoxy or polyester). Common properties: Stiff, strong and flexible. Low density, More expensive, Strength per unit mass (specific strength) is very high with respect to metals and ceramics, Some of them are used in some aircraft and aerospace applications, high-tech sporting equipment (e.g., bicycles, golf clubs, tennis rackets, and recently in automobile bumpers. HA/PE, silica/SR, carbon fiber/ultra high molecular weight polyethylene (CF/UHMWPE), carbon fiber/epoxy (CF/epoxy), and CF/PEEK are some examples of polymer composite biomaterials In a composite material, the component forming the major and continuous phase (>50% by volume, usually having relatively low stiffness and strength) is termed “matrix” and the component existing as a minor, discontinuous, and dispersed phase (