BMED 420 Notes PDF

Introduction to Biomaterials What is a biomaterial? ​ A biomaterial is a material used for medical applications to support, enhance, or replace damaged tissue or a biological function ○​ In close contact with living tissue ​ “Bio” = bio-compatible...

Introduction to Biomaterials What is a biomaterial? ​ A biomaterial is a material used for medical applications to support, enhance, or replace damaged tissue or a biological function ○​ In close contact with living tissue ​ “Bio” = bio-compatible ​ Can be natural or synthetic ​ Can be therapeutic or diagnostic ​ Generally implanted Applications of biomaterials ​ Medical implants ​ Methods to promote healing ○​ Sutures, staples, etc ​ Regenerated human tissues ○​ Tissue engineering ​ Biosensors ○​ Glucose monitoring devices ​ Drug delivery systems Important attributes of a biomaterial ​ Biocompatibility = no harm to the host body ○​ Non toxic ○​ Non allergenic ○​ Non thrombogenic ○​ Non carcinogenic ○​ Non mutagenic ○​ Non inflammatory ​ Appropriate mechanical properties for the job ○​ Aim to match native tissue Four ways a biomaterial can interact with the body ​ Hurt you ​ Dissolve ​ Be surrounded by a protective layer ​ Bond/integrate with tissue Types of biomaterials: ​ Metals ○​ Composed of one or more metallic elements and small amounts of nonmetallic elements ○​ Metallic bonds ○​ Atoms arranged in an orderly structure ○​ Good conductors of electricity and heat ○​ Ductile (can deform before breaking) ○​ Strong, tough, prone to corrosion ​ Polymers ○​ Broad class of compounds based on nonmetallic elements ​ Can be natural or synthetic, mostly organic  ○​ Typically composed of intertwining long chains of large molecules with a carbon backbone and covalent bonds ○​ Low conductivity of heat and electricity ○​ Ductile, usually soft and compliant, but can be rigid ○​ Low strength and mechanical properties, but good corrosion resistance ​ Ceramics ○​ Inorganic compound of metallic and nonmetallic elements ○​ Can have covalent (shared electrons) or ionic bonds (transferred electrons) ○​ Insulator of heat and electricity ○​ Thermally stable, good for high temperature applications ○​ Brittle, hard, and rigid ○​ Resistant to wear, friction, and corrosion ​ Composites ○​ Composed of multiple materials ​ Best of both worlds, but expensive ○​ Usually synthetic but some natural composites exist ​ Bone (cellulose and lignin polymers ​ Bone (collagen and hydroxyapatite) Summary: ​ Biomaterials must be biocompatible (not cause harm to the body) and have appropriate mechanical properties for the job ​ Biomaterials can hurt you, dissolve, be surrounded by a proactive layer, or integrate with tissue ​ Main types of biomaterials: metals, ceramic, polymers, and composites ○​ Metals are ductile and strong but prone to corrosion ○​ Ceramics are hard and resistant to corrosion but brittle ○​ Polymers are composed of long chains are typically ductile and resistant to corrosion but have lower mechanical properties Metals, Ceramics, and Polymers as Biomaterials Metals as biomaterials ​ Common metals for biomaterials: titanium, stainless steel, cobalt-chromium, nitinol, gold ○​ Most other metals are not biocompatible ​ Pros: strong, resistant to fatigue, ductile, easily sterilized ​ Cons: subject to stress shielding, corrosion, and wear ​ Stainless steels, cobalt, and titanium based alloys are used for orthopaedics ​ Nitinol has shape memory ​ Magnesium is biodegradable Metals in orthopaedics ​ Stainless steel ○​ Biocompatible and low cost but poor corrosion resistance ○​ Applications: temporary devices (fracture plates, screws, nails) and some permanent implants ○​ 316L is the most common ○​ Can enhance corrosion resistance by alloying and metallurgical processing  ​ Cobalt-chromium alloys ○​ Superior to stainless steel in corrosion resistance and fatigue strength ○​ Expensive, can be toxic/allergenic, and induce stress shielding ○​ Applications: load-bearing implants (hip implants, knee and ankle prostheses ○​ Can alloy to increase corrosion resistance and strength ​ Titanium ○​ Best corrosion resistance and biocompatibility, light weight, less stress shielding, good bone bonding, poor bending ductility, poor wear resistance ○​ Applications: permanent devices (hips, pacemakers, dental implants, bone rods, etc) ​ Shape-memory alloys ○​ Shape-memory property of nitinol is useful for self-expandable stents, clamps, and clips ○​ Mixed studies on biocompatibility, concern over nickel ion release ○​ Expends to original shape in body temperature Metals in dental applications ​ Fillings, crowns, bridges, and root replacements used chromium and titanium ​ Orthodontics like braces and retainers use nitinol Biomaterial classifications ​ Biotolerant: accepted but encapsulated with scar tissue ​ Bioinert: direct contact with no tissue reaction ​ Bioactive: bonds/integrates with tissue ​ Biodegradable: dissolves and is replaced with tissue Magnesium alloys ​ Degradable ​ Applications: tissue engineering and resorbable screws ​ Safety concerns related to metal toxicity Ceramics and biomaterials ​ Common materials: alumina, zirconia, bioglass, hydroxyapatite, calcium phosphate ​ Pros: strong, chemically inert, high compressive strength, biodegradable or bioactive ​ Cons: hard to manufacture, brittle, fracture, can loosen, only compressive strength Types of bioceramics ​ Alumina and zirconia are bioinert and used for dental and hip implants ​ Hydroxyapatite and calcium phosphate are bioactive and used for cement, coatings, and scaffolds ○​ Also biodegradable and can be replaced by native tissue Polymers as biomaterials ​ Common materials: silicone, PEEK, PTFE, polyethylene, PMMA, hydrogels, nylon, etc ​ Pros: easy to manufacture and modify, can be bendable and biodegradable ​ Cons: poor strength, prone to wear and tear ​ Can be bioinert or biodegradable, usually not bioactive ​ Smart polymers can respond to stimuli Structure of polymers ​ Thermoplastics: linear and branched chains ​ Thermosets: crosslinked and networked chains Composites as biomaterials ​ Can be strong and lightweight, corrosion resistant, high cost, difficult to change shape The Body’s Response to Biomaterials Local responses to biomaterials ​ Response at the site of the implant or device ​ Can be caused by the material or trauma/surgery ​ Inflammation ○​ Part of your natural immune response ​ Complex reaction of tissue to local injury ​ Body tries to contain or neutralize injurious agent and heal the site ○​ Intensity/duration of inflammation varies on size/shape/properties of material ○​ Clinical features: redness, swelling, heat, pain ○​ Can be acute or chronic ​ Encapsulation - bad ○​ Foreign body response refers to the immune response to the implant, ultimately leading to encapsulation ​ An attempt to protect the body, but may affect implant function ○​ Can coat or modify device surface to make this effect temporary ​ Biointert with only a thin layer of collagenous tissue ​ Acute inflammation: immediate and early response ○​ Characterized by fluids and plasma exuding into tissue ○​ Accumulation of neutrophils ​ Chronic inflammation: longer term response ○​ Leads to repair or foreign body response ○​ Involves macrophages ​ Thrombosis ○​ Blood-material interaction that triggers coagulation pathways ​ Infection ○​ Bacteria can attach to the surface ​ Can be introduced through surgery ○​ May prevent tissue integration ○​ Can affect device function ○​ Can lead to systemic infection if it spreads into the bloodstream ○​ Can add antimicrobial coatings ○​ Most common serious complication of medical devices ​ Tumorigenesis ○​ Implanted material can elicit excessive and uncontrolled cell proliferation ○​ Can be benign/local or malignant ○​ Can invade neighboring tissues or bloodstream to become systemic Foreign body response ​ Proteins adsorb to device surface ​ Neutrophils try to break down the surface ​ Macrophages degrade the surface ​ Giant cells are formed ​ Fibroblasts come to the site ​ Device becomes encapsulated Systemic response to biomaterials ​ Response throughout the body ​ Toxicity ○​ Release of wear and corrosion particles ○​ Release of nickel and chromium alloys can lead to muscle pain, decline in cognitive function, memory difficulties, etc ○​ Additives can be irritants and induce systemic immune reaction ○​ Chemical substances in implants can be carcinogens ○​ Need to minimize corrosion ○​ Corrosion: destruction of metal by electrochemical reactions ​ Galvanic corrosion: two different metals in electrical contact ​ Hypersensitivity ○​ Known as intolerance ○​ Discussed in relation to metals ○​ Undesirable reactions produced by normal immune system, allergies and autoimmunity ​ Thromboembolism ○​ Local blood clot breaks off and travels through circulation to block another vein/artery ○​ Biggest risk is venous thromboembolism leading to pulmonary embolism Bioactive Materials and Surface Modifications Why modify surfaces? ​ Surface features have the most impact on the biocompatibility of a material ​ Bulk material governs mechanical properties, durability, and functionality ○​ Want to maintain build properties, but modify the surface on a nanometer scale ​ Enhance biocompatibility, increase hardness, enhance corrosion resistance Controlling protein adsorption ​ Implanted material is immediately coated with proteins ​ Cells attach to the proteins and interact with them ​ Control over protein adsorption gives you control over cellular processes ○​ Can prevent a foreign body response Main types of surface modifications ​ Surface coatings ○​ Increase attachment strength at tissue-implant interface ○​ Increase surface area ○​ Decrease friction, increase corrosion and wear resistance ○​ Decrease infection ​ Surface patterning ○​ Nanoscale topographical features that give the body physical cues that allow for normal cell adhesion to form a base for normal tissue growth ​ Surface roughening ○​ Increased surface area leading to increased bioactivity ​ Plasma modification ○​ Change surface energy ​ There are others Hydrophobic and hydrophilic surfaces ​ Hydrophobic: water fearing, surface will not interact with water ○​ High contact angle ○​ Want to shed as much water as possible ○​ Bind to proteins more firmly than hydrophilic surfaces ○​ Self-cleaning ​ Repel fluids ​ Surgical tools, urine cups, diagnostic devices, drug delivery ○​ Reduces risk of infection ​ Hydrophilic: water loving, surface will interact with water ○​ Low contact angle ○​ Liquid evenly spreads across surface ○​ Lubricity reduces force required to manipulate intravascular medical devices ​ Can decrease frictional force, reducing risk of damage to blood vessel walls ​ Catheters, guide wires, etc ○​ Reduces thrombogenicity ​ Determined how material interacts with the body Mechanical Properties of Materials How can we design for success? ​ Choose materials with appropriate mechanical properties for the intended use ○​ Mechanical properties for a stent should differ from a hip implant ○​ Conduct mechanical testing of device under simulated anatomical conditions ​ Choose materials with properties closest to native material properties Stress shielding and Wolff’s Law ​ Wolff’s Law: bone will remodel based on the loads placed upon it ​ Stress shielding: a device that is too strong with weaken surrounding bone Mechanical properties important to biomaterials ​ Young’s modulus ​ Ultimate tensile strength ​ Fracture toughness ​ Elongation at break ​ Ultimate compressive strength Biomaterial Fatigue and Failure Fatigue ​ Most biomaterials will need to withstand repetitive loading in the body ​ Fatigue testing involves applying cyclic loading to determine fatigue lids and crack growth data, identify critical locations, and demonstrate safety ​ Fatigue fracture is the main cause of premature failure in biomedical implants ○​ Can arise from tiny defects that grow ​ Non homogeneity in microstructure ​ Manufacturing defects ​ Under cyclic loading, a material can fracture below its UTS or yield strength ​ Fatigue is the progressive structural damage that occurs under cyclic loading ○​ Under static loading fracture can only occur after UTS Failure ​ Tend to be associated with tensile and bending instead of compressive loads ​ Damage is irreversible ​ Influenced by temperature, surface finish, oxidizing chemicals, etc ​ Fretting fatigue = cyclic stress + friction ○​ Normal stress and shear stress between components against bone ​ Corrosion fatigue = cyclic stress + corrosion ○​ Development of brittle cracks leading to growth and failure Wear ​ Caused by friction ​ Can lead to aseptic loosening ○​ Generation of tiny particles around the device ○​ Particles that attract macrophages ○​ Dying macrophages break down and release acidic enzymes that can cause erosion ​ Concerns over toxicity of metal wear particles and ions ​ Wear resistance is closely controlled by hardness ○​ Can improve with surface modification like zirconia coating Hardness ​ Measures local deformation to an indenter ○​ Hard materials are resistant to wear and direction ​ Most popular tests are Brinell and Rockwell ​ Hardness is roughly proportional to tensile strength ○​ Can estimate tensile strength without a tensile test ​ Brinell hardness measures the diameter of penetration indenter ​ Rockwell hardness measures the depth of penetration of diamond indenter In Vitro Testing of Biomaterials Evaluation of biomaterials: ​ Must validate: ○​ Material properties ​ Material testing  ○​ Biological effects ​ Bench (in vitro) ​ Animal models (in vivo) ​ Clinical trials ​ Post-implantation follow-up studies ​ In vitro: in a test tube or outside an organism ​ In vivo: in an organism ​ Ex vivo: in tissues explained from an organism ​ In situ: in original position In vitro testing ​ Use testing standards (ISO and ASTM) ○​ Ensures safety and effectiveness ○​ Quick turnover, high throughput screening, low cost ​ Compare with SRM (standard reference material/control) ○​ SRM should be clinical gold standard biomaterial for that application Cytotoxicity testing ​ ISO 10993-5: Tests for Cytotoxicity ○​ Most important in vitro test ​ Prescribed for every type of medical device ​ Good first step, gives initial biocompatibility ​ Tests are sensitive, cheap, and quick ○​ Negative: free of harmful leachables, or insufficient amount to cause acute effect ○​ Positive: warning sign, material could have harmful leachables, need more tests ​ Cell monolayers are grown to 70-80% confluence and exposed to test and control samples ○​ Contact method: apply material directly, used for patches/contact devices ○​ Elution method: uses a solvent to extract one material from another, more relevant ​ Signs of cell toxicity: morphological changes and cell death Hemocompatibility ​ ISO 1993-4: Selection of Tests for Interaction with Blood ○​ No standard methods that can predict hemocompatibility across devices and applications ○​ Based on blood contact category, it recommends tests for thrombosis, coagulation, platelet function, hematology, and immunology ​ Cytotoxicity to blood can cause significant harm ○​ Hemolysis: breakdown of red blood cells impairs oxygen transport ○​ Adverse reactions with white blood cells impair body’s ability to fight pathogens ○​ Adverse reactions with cells involved in clotting can lead to blood device Genotoxicity testing ​ ISO 10993-3: Tests for Genotoxicity, Carcinogenicity, and Reproductive Toxicity ○​ Required for devices in contact with the body for >30 days ○​ Assay are done to ensure material is not a: ​ Genotoxic mutagen: agent that changes genetic material (DNA) ​ Carcinogen: agent that causes uncontrolled proliferation of host cells Chromosomal aberration and DNA effects tests ​ Can be in vitro or in vivo  ​ Chromosomal aberration tests: detects chromosomal damage ​ DNA effects tests: detects DNA damage Cell adhesion testing ​ Want adhesion of some cells ​ Don’t want adhesion of inflammatory cells ​ Cells do not interact with material, they interact with proteins adsorbed to the material surface ​ Cells culture on biomaterials can be visualized using microscopy In vivo testing ​ In vitro assays do not reproduce the complexity of an in vivo situation ○​ Might find that a new biomaterial coating does not improve cell attachment in vitro but does in vivo ​ Both in vitro and in vivo testing must be done In Vivo Testing of Biomaterials In vivo testing ​ Must follow testing standards and compare with SRMs ​ Goal is to take measurements of cell and tissue-level responses to an implanted biomaterial ​ Must: ○​ Provide an environment that closely matches the biological environment in which the material will be used ○​ Provide quantifiable outcome measures ○​ Detect and precinct clinically relevant differences across materials tested Implantation testing ​ ISO 10993-6: Tests for Local Effects Following Implantation ​ Implant material in muscle and examine local reaction at site ○​ Presence of inflammatory cells ○​ Extent of fibrosis ○​ Scored quantitatively using ISO’s scoring recommendations ​ Set implant intervals to time of human exposure or show the reaction has stabilized Irritation and sensitivity testing ​ ISO 10993-10: Tests for Irritation and Sensitization ○​ 3 in vivo tests ​ Primary skin test (material placed on shaved back of rabbits for 4-24 hours) ​ Ocular irritation test (material placed in rabbit’s eye) ​ Intracutaneous injection (material injected into rabbit’s skin) System toxicity testing ​ ISO 10993-11: Tests for Systemic Toxicity ​ Acute toxicity of metal ions is tested using animal models ○​ Most injection test (sensitization) ○​ Oral and dermal tests (irritation/inflammation) ○​ Pyrogen test (fever response) ​ Subchronic testing: tissue exposure or repeated treatment up to 10% of animal lifespan ○​ Necessary for devices in contact with patients for 1-30 days ​ Chronic testing: tissue exposure or repeated treatment for less than 10% of animal lifespan Selection of animal models ​ Select animal model based on device location and function ○​ Sheep and goats closest to human bone pathology Variables in animal testing ​ Species, age, gender ○​ Ovariectomized rodents are used to mimic endocrine status of postmenopausal women ​ Diet ○​ Calcium-deficient diet mimics postmenopausal nutritional state in women that leads to osteoporosis ​ Size of defect ○​ Critical-sized defect that won’t heal on its own, varies among species and sites Ethical issues ​ Increasing concern for well-being of animals ​ Duty to ensure animals are treated humanely ​ Research centers have committees to maintain approval for animal trials ​ While R&D can begin in vitro, animal studies are required to assess safety and efficacy The 3 R’s ​ Replace ○​ Replace animal studies with other methods ○​ Full replacement: avoids using any animals ​ Includes use of human volunteers, tissues, cells, and computer models ○​ Partial replacement: includes use of animals that are not capable of suffering ​ Reduce ○​ Reduce number of trials on animals ○​ Appropriately design experiments to ensure robust and reproducible findings ○​ Maximize information gathered per animal ​ Balance against additional suffering caused by repeated use ○​ Sharing data and resources between research groups ​ Refine ○​ Minimize stress of animals ○​ Use humane housing, feeding protocols, handling, etc ○​ Use appropriate anesthesia to minimize pain ○​ Train animals to cooperate with procedures ​ ISO 10993-2: Animal Welfare Requirements ○​ Specifies minimum requirements to ensure that proper provision has been made for welfare of animals in biocompatibility testing ○​ Offers guidance on the 3 R’s Degradable biomaterial considerations ​ Often used as scaffold material for tissue engineering ​ Must be biocompatible and degradation products should be non-toxic ​ Degradation rate should be tuned to match formation rate of functional tissue ​ The soluble biomaterial degradation products are transported via lymphatic system to kidneys then excreted Degradation of polymers ​ Can degrade due to heat, light, or chemicals ○​ Degradation is often intentional ​ Long polymer chains break down to shorter segments and lose structural/chemical properties, leading to cracking and disintegration Hydrolytic degradation ​ Hydrolysis: breakdown of material due to reaction with water ○​ Bonds are cleaved ​ Occurs in polymers with hydrolyzable groups along the main chains ​ Polyesters are the most common biodegradable polymers that undergo hydrolysis Benefits of biodegradable polymers ​ No requirement of second surgery ​ Eliminate chronic inflammation ​ Deliver drugs through degradation ​ Useful for tissue engineering Factors that affect rate of degradation ​ Nature of chemical bond ​ pH ​ Polymer composition ​ Extent of water uptake ​ Hydrophilicity of material ○​ Hydrophobic has slower degradation, less water diffusion ​ Molecular weight of polymer Bulk vs. surface degradation ​ Degradation leads to erosion ​ Surface erosion: polymer degrades from exterior surface ○​ Water erodes surface ​ Bulk erosion: degradation occurs throughout whole material equally ○​ Strength decreases more quickly overtime ​ Many materials undergo a combination Ceramic degradation ​ Most common: calcium phosphates and bioactive glass ○​ Unique bone-bonding properties ○​ Can modulate degradation profile by mixing different ceramics Metal degradation ​ Magnesium is the main biodegradable material ○​ Light, biocompatible ○​ Degrades too fast for some applications; can apply calcium phosphate coatings to control degradation rates to match the kinetics of bone healing Regulatory Pathways FDA organization ​ Office of Medical Products and Tobacco ○​ CBER: Center for Biologics Evaluation and Research  ○​ CDER: Center for Drug Evaluation and Research ○​ CDRH: Center for Devices and Radiological Health Classes of medical devices ​ Class I: low risk ○​ Bandages, stethoscopes, gloves, masks, tongue depressors, toothbrushes, etc ​ Class II: moderate risk ○​ Blood pressure cuffs, pregnancy tests, syringes, blood transfusion devices, contacts, etc ​ Class III: high risk ○​ Stents, implants, pacemakers, etc FDA approval pathways Exempt devices ​ 93% of Class I devices and 8% of Class II devices are exempt from 510(k) ​ Manufacturer is responsible for: ○​ Good manufacturing processes (GMP) ○​ Quality assurance (QA) ○​ Documentation 510(k) premarket notification ​ Most common pathway ​ 92% of Class II devices are subject to 510(k) ​ Manufacturer is responsible for: ○​ Demonstrating substantial equivalence through performance testing ​ Mechanical testing ​ Sometimes bench or animal testing, only some require clinical data ​ Special controls include device specific performance standards, labeling, data, guidelines, etc ​ Must demonstrate the device is as safe and effective as an existing legally marketed device ​ FDA decides within 90 days if it’s substantially equivalent (SA) ○​ Otherwise, goes through pre-market approval (PMA) route Device testing for 510(k) ​ Common: ○​ Bench testing ​ Electrical/software ​ Mechanical ○​ Biocompatibility ○​ Sterility and shelf life ​ Much less common ○​ Animal and clinical testing Types of FDA review decisions ​ Substantially equivalent (SE) ○​ Clearance to market a new device ​ Unable to determine ○​ May be required to submit additional information ​ Not substantially equivalent (NSE) ○​ Sponsor may appeal decision ○​ Submit a PMA ○​ Submit a new 510(k) ○​ Initiate De Novo Process Pre-market approval (PMA) ​ Almost all Class III devices ​ Manufacturer is responsible for: ○​ Demonstrating reasonable assurance of safety and effectiveness ○​ Performance testing ○​ Bench, animal, and clinical testing ○​ Post-approval requirements De Novo classification ​ If 510(k) review leads to NSE decision, it is automatically Class III ​ Criteria: clinical benefit, simple technology, no predicate, low-moderate risk Regulatory guidance ​ Several resources exist to help guide you through the process to safely and effectively develop a medical device ​ Main documents: FDA CFR 21, ISO 13485:2016, etc Things can go wrong ​ Infections, corrosion, mechanical failure, etc ​ May lead to litigation cases and recalls ○​ Medical device records (MDR): information on recalls ○​ MAUDE database: individual medical reports ​ All medical devices carry some level of risk ○​ Important to identify root cause of risk ​ Device factors, surgical factors, patient factors, use factors, etc Key takeaways ​ FDA classifies device as I, II, or III  ○​ Most class I devices are exempt; FDA registered/listed ○​ Most class II devices go through the 510(k) pathway; FDA clearance ○​ Most class III devices need pre-market approval (PMA); FDA approval Orthopaedics: Anatomy and Pathologies Musculoskeletal system ​ Made up of bones, muscles, cartilage, tendons, ligaments, joints, and other connective tissue that attached tissue and holds organs together ○​ Tendons connect muscle to bone ○​ Ligaments connect bone to bone Which fails first? ​ The majority of musculoskeletal problems are related to our joints ​ Common problems with aging: ○​ Cartilage starts to wear away ​ Osteoarthritis ○​ Tissues become stiffer and less flexible ○​ Fluid in joints and bone density decrease Composition of musculoskeletal tissues ​ Cells surrounded by ECM ​ ECM is made up of different amounts of: ○​ Collagen (types I-V) (protein) ○​ Proteoglycan (non-collagenous protein) ○​ Water ○​ Elastin (extensible tissues) ○​ Hydroxyapatite (bone only) Structure of bone ​ Cortical (compact) ○​ 80% of total bone mass of the body ○​ 3-4% porosity ​ Trabecular (cancellous/spongy) ○​ 30-90% porosity ○​ More active in remodeling than cortical bone Bone cells ​ Osteoclasts resorb bone ​ Osteoblasts synthesize bone ○​ Service from osteogenic stem cells ​ Osteocytes are formed from osteoblasts and maintain bone Types of cartilage ​ Elastic cartilage (most flexible) ○​ Ear, auditory tube, larynx ​ Hyaline cartilage (second most flexible) ○​ Articular cartilage in joints, cartilage end plate in spine, nose, lungs ​ Fibrocartilage (least flexible) ○​ Annulus fibrosus (disc), between pubic bones, resists tension and compression Types of joints ​ Fibrous: ​ Cartilaginous: ​ Synovial: Disc anatomy ​ Resist loading in many directions ​ Lamellae layered at alternating 30 degree angles ​ Annulus fibrosus (outer region) ○​ 15% type I and II collagen ○​ 70% water ○​ 5% proteoglycan ○​ Encases nucleus and resist multi-axial loading on the spine ​ Nucleus pulposus (center of disc) ○​ 4% type II collagen ○​ 77% water ○​ 14% proteoglycan ○​ Proteoglycan aggregates draw water into disc creating pressure to maintain height and resist compressive loading ​ Cartilage endplate ○​ 25% type I collagen ○​ 55% water ○​ 8% proteoglycan ○​ 0.1-2 mm thick ○​ Resists compression and allows for nutrient transport ​ Largest avascular structure in the body ○​ Needs to get nutrients from surroundings Back pain ​ The most common musculoskeletal condition, affects 80% of people ​ 90% of back pain is nonspecific ​ Lack of accurate diagnosis has implications for treatment ​ Most commonly stems from intervertebral disc pathologies Disc pathologies ​ Degenerated: ​ Bulging: ​ Herniated: ​ Thinning: ​ Osteophytes: Hip anatomy and pain ​ Ball and socket joint ○​ Head of femur fits into acetabulum ​ Hip fracture ○​ Often caused by osteoporosis ​ Osteoarthritis ○​ Most common reason for hip replacement Knee anatomy and pain ​ Femur, tibia, and fibula ○​ Connected by ACL and PCL ​ ACL tear is the most common knee injury ​ Meniscus damage and wear Shoulder anatomy and pain ​ Humerus attached to scapula (shoulder blade) and clavicle (collar bone) ​ Shoulder pain causes: ○​ Rotator cuff tear ○​ Calcific tendonitis ○​ Bicep tendonitis ○​ Shoulder osteoarthritis Orthopaedics: Hardware Solutions Types of orthopaedic hardware ​ Screws, plates, pins ​ Wires, rods, nails, suture anchors ​ Spinal cages and joint replacements Implants used in spinal fusion ​ Screws and rods ○​ Rods stabilize vertebral segments ○​ Screws act as anchor points for rods ​ Placed at 2 more consecutive spine segments ○​ Most screws and rods are permanent, but some can be removed after bone graft grows ​ Cages/disc spacers ○​ Cages have grooves, holes, or pores to allow bony ingrowth ○​ Sometimes add bone graft material Hip implant combinations ​ Metal on metal ○​ Concerns with metal debris from corrosion ​ Metal/ceramic on polyethylene ○​ More wear and aseptic loosening ​ Ceramic on ceramic ○​ Inert, but expensive and brittle Suture anchors ​ Arthroscopy: minimally invasive surgical technique that uses an endoscope and small instruments to treat soft tissues through a series of small incisions ​ Suture anchors: used to fasten ligaments and tendons to bones via sutures ​ First generation: stainless steel and titanium ○​ Issues: loosening and migration, interference with MRI, cartilage injury ​ Next generation: bioabsorbable polymers ○​ Issues: low mechanical strength, breakage, degrade too quickly, implant debris ​ Next generation: biodegradable composites ​ Best of all worlds: PEEK, not biodegradable PEEK (polyetheretherketone) ​ Strong (high holding strength) ​ Soft ○​ Less risk of cartilage damage from wear ○​ Can be drilled through in event of revision surgery ○​ Better manufacturability than metals ​ Radiolucent: transparent to x-rays ​ Carbon-reinforced PEEK anchors combine benefits of radiolucency and mechanical properties similar to bone Vented suture anchors ​ Can promote bone marrow flow and bony ingrowth ​ Smith & Nephew HEALICOIL PK Orthopaedics: Grafts and Tissue Engineering Tissue grafts ​ Autograft: tissue graft of patient’s own tissue ○​ Pros: ​ No immune response or risk for rejection ​ Promotes osteogenesis ​ Stronger than tissue that has been sterilized ○​ Cons: ​ Cell culture takes time ​ Requires second surgical site ​ Often inadequate amount of tissue can be harvested ​ Allograft: tissue graft from donor of same species ○​ Pros: ​ Unlimited supply ​ No size limitation ​ Shorter operation time ○​ Cons: ​ Immune response ​ Delayed incorporation ​ Sterilization makes tissue weaker ​ Xenograft: tissue graft from donor of different species Allogeneic response ​ Potent immune response that can cause allograft rejection ​ T cells = part of immune system that focus on foreign particles ○​ Cells that attack already-infected cells (transplanted cells) Autografts for spinal fusion ​ Bone graft, in addition to disc spacer, provides foundation for new bone to grow (fusion) ​ Gold standard = autograft ○​ Greater fusion success ○​ Harvest from iliac crest, rib, or spine ○​ Can use a combination of trabecular bone and cortical Allografts for spinal fusion ​ Generally frozen or freeze dried to limit chance of graft rejection ​ Do not contain living bone cells, not as effective at stimulating fusion Bone graft substitutes/extenders for spinal fusion ​ Demineralized bone matrix (DBM) ○​ Allograft bone where mineral content has been removed to expose bone-forming proteins ​ Ceramic-based bone graft extenders ○​ Ceramics provide matrix fusion ○​ Mixed with regular bone ​ Bone morphogenetic protein ○​ Found in bone; produced in larger amounts by genetic engineering ○​ Can be added to promote new bone growth ​ Osteoconductive: provides structural matrix for bone growth ​ Osteoinductive: stimulates new bone growth ACL grafts ​ Autografts ○​ Patellar tendon - gold standard ○​ Hamstring tendon ○​ Quadricep tendon ​ Allograft ○​ Achilles tendon ○​ Hamstring tendon ○​ Patellar tendon ​ Z-lig xenograft ○​ Porcine derived, no live cells ○​ Highly scalable ○​ ACL xenografts are largely unsuccessful Smart Implants and Bio-Inspired Design Smart devices ​ Smart devices are creating a paradigm shift from episodic monitoring to continuous sensing and integrated healthcare ○​ Detect problems early and provide minimally invasive management ○​ Enable people to be in control of their own health ​ Bi-directional data can be used to close the loop and tailor therapies according to feedback ​ Smart implants take advantage of implanting hardware in the body Bio-inspired design ​ Bio-inspired design (biomimetics): translation of knowledge obtained from the natural world into new innovations ​ 3 main applications: ○​ Implanted materials inspired by native human bone/tissue ○​ Implanted materials inspired by other animal tissues/features ○​ Non-medical materials inspired by native biomaterials but used for other purposes