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    Biocompatibility: Biological Response Biocompatibility Tests Sterilization Issues

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    bagus3869
    This document discusses biocompatibility, which refers to the ability of a material to perform with an appropriate host response in a specific application. It describes the biological response to implantation, including inflammation, foreign body reaction, and fibrosis. Proper testing of new biomaterials is important according to FDA regulations to ensure biocompatibility prior to implantation in humans. Different sterilization methods can impact the material properties and shelf life of implants.

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    Biocompatibility: Biological Response Biocompatibility Tests Sterilization Issues

    Uploaded by

    bagus3869
    221 views41 pages
    This document discusses biocompatibility, which refers to the ability of a material to perform with an appropriate host response in a specific application. It describes the biological response to implantation, including inflammation, foreign body reaction, and fibrosis. Proper testing of new biomaterials is important according to FDA regulations to ensure biocompatibility prior to implantation in humans. Different sterilization methods can impact the material properties and shelf life of implants.

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    Biocompatibility

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    This document discusses biocompatibility, which refers to the ability of a material to perform with an appropriate host response in a specific application. It describes the biological response to implantation, including inflammation, foreign body reaction, and fibrosis. Proper testing of new biomaterials is important according to FDA regulations to ensure biocompatibility prior to implantation in humans. Different sterilization methods can impact the material properties and shelf life of implants.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    221 views41 pages

    Biocompatibility: Biological Response Biocompatibility Tests Sterilization Issues

    Uploaded by

    bagus3869
    This document discusses biocompatibility, which refers to the ability of a material to perform with an appropriate host response in a specific application. It describes the biological response to implantation, including inflammation, foreign body reaction, and fibrosis. Proper testing of new biomaterials is important according to FDA regulations to ensure biocompatibility prior to implantation in humans. Different sterilization methods can impact the material properties and shelf life of implants.

    Copyright:

    Attribution Non-Commercial (BY-NC)
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    Download as ppt, pdf, or txt
    of 41

    Biocompatibility

    Biological response
    Biocompatibility tests
    Sterilization Issues
    Biocompatibility

    • Arises from differences between living and non-


    living materials
    • Bioimplants trigger inflammation or foreign body
    response
    • New biomaterials must be tested prior to
    implantation according to FDA regulation
    • WWII: Validated biocompatibility of several
    materials including PMMA
    Biomaterial-Tissue Interactions
    Definitions
    • Neutrophil- common leucocyte of the blood- short-lived phagocytic cell
    • Lymphocyte- small cell in blood- recirculates through tissues and back through lymph
    --polices body for non-self material-- recognizes antigens through surface receptors
    • Antigen- produces antibody- stimulate adaptive immune response
    • Antibody- Serum globulins with wide range of specificity for different antigens-- bind
    to surface
    • Monocyte- largest nucleated cell of blood-develops into macrophage when it migrates
    to tissues
    • Macrophage- phagocyte--scavenger cell-- of tissues
    • Lysozyme- enzyme secreted by macrophages- attack cell wall of bacteria “natural
    antibiotic”
    • Mast Cell- large tissue cell which releases inflammatory mediators-- increases
    vascular permeability-- allows complement to enter tissues from blood
    • Complement- a series of enzymes in blood- when activated produce inflammatory
    effects
    Response to implantation

    • Inflammation
    • Acute inflammation
    • Chronic inflammation
    • Granulation tissue
    • Foreign Body Reaction
    • Fibrosis and Encapsulation
    Inflammation

    • Inflammation is the reaction of vascularized


    living tissue to injury.
    • The inflammation process includes a sequence of
    events that can heal the implant site.
    • This is done through the generation of new tissue
    via native parenchymal cells or the formation of
    fibroblastic scar tissue.
    Inflammation process

    • Enhanced permeability of
    vasculature
    • Fluid, proteins, blood cells escape
    vascular system into the injured
    tissue
    • Blood clotting --thrombosis is
    possible
    • Cell response--neutrophils (24-48
    hrs)
    • Monocytes macrophages (months)

    Marieb, EN and Mallatt, J. 1997. Human


    Anatomy
    Acute Inflammation
    • Short term (minutesdays)
    • Exudation of fluid, plasma, proteins, and
    leukocytes (neutrophils).
    • Phagocytosis and enzymatic release occurs.
    • Activation of neutrophils and macrophages--digest foreign material--
    involves recognition, attachment, engulfment, and degradation.
    • Recognition and attachment is enhanced when serum factors,
    Opsonins present—immunoglobin G (IgG), complement activated
    fragment C3b--can adsorb to biomaterials.
    • Neutrophils and macrophages have receptors for these proteins.
    • Due to size disparity, however, frustrated phagocytosis may occur—
    this results in extracellular release of leukocyte products in a cellular
    attempt to degrade the biomaterial.
    Chronic Inflammation

    • Long term (≥≥ days).


    • Characterized by the presence of
    macrophages, monocytes, and
    mononuclear cells including lymphocytes
    and plasma cells.
    • Accompanied by the proliferation of
    blood vessels and connective tissue.
    • Lymphocytes and plasma cells are
    involved in the immune reactions-
    mediate antibody production. www.lumen.com
    • Macrophages process and deliver
    antigen to immunocompetent cells—
    mediate immune reactions.
    Cellular pathways

    • Macrophages along with monocytes belong to the mononuclear


    phagocytic system (MPS) or the reticuloendothelial system (RES).
    • These systems include the cells in the bone marrow, peripheral
    blood, and specialized tissues (liver, lung, connective, lymphoid).
    • The macrophage is a key cell in the inflammation process as it can
    produce a large number of biologically active products including
    proteases, complement components, coagulation factors, growth
    factors and cytokines (proteins that regulate immune response).
     Growth factors include (FBF)-fibroblast growth factor, (TNF) tumor
    necrosis factor, (IL-1) interleukin-1... These are important for the
    growth of fibroblasts, blood vessels, epithelial cells... and play a key
    role in tissue remodeling and wound healing.
    Biological Response

    Corrosion, Wear, Fracture

    Osteolysis
    DEBRIS

    CYTOKINES FOREIGN
    BODY
    RESPONSE
    Wear-Mediated Osteolysis

    Wear particles from


    the replacement head
    and liner cause
    inflammation that can
    lead to pain, bone
    loss, and ultimately
    revision surgery
    wear
    particles

    bone loss

    Archibeck, MJ; Jacobs, JJ; Roebuck, KA; Glant, TT. Journal of Bone & Joint Surgery, 2000
    Granulation tissue
    • Within 24 hrs of implantation, healing initiated by
    the action of monocytes and macrophages.
    • Fibroblasts and vascular endothelial cells reproduce
    and form granulation tissue (pink, granular
    appearance)
    • Neovascularization involves the generation,
    maturation, and organization of endothelial cells into
    capillary tubes.
    • Fibroblasts are active in the synthesis of
    proteoglycans and collagen (type III predominantly).
    • Granulation tissue may be observed within 3-5 days
    of implantation of a biomaterial—it is often
    accompanied by wound contraction.
    Foreign Body Reaction

    • Indicated by the presence of multinucleated


    foreign body giant cells and the components
    of granulation tissue (macrophages,
    fibroblasts, and capillaries)
    • Observed in silicone breast implants
    • Surface of the biomaterial will often
    determine the composition of the foreign
    body response
    Surface structure important for
    biocompatibility
    • High surface to volume ratio of
    fabrics and porous structures can
    result in higher ratios of
    macrophages than a smooth
    component made of the identical
    material but can also encourage
    tissue ingrowth --this is observed in
    vascular grafts.
    Fibrosis and Encapsulation
    • The final stage of the foreign body response and healing
    process is the development of a fibrous encapsulation
    (porous structures may be excluded from this stage due to
    tissue ingrowth).
    • Repair involves two separate processes: replacement of
    tissue by parenchymal cells of the same type or replacement
    by connective tissue that constitute the fibrous capsule.
    • These processes are controlled by the growth capacity of
    the cells in the tissue receiving the implant, the persistence
    of the tissue framework and degree of injury.
    Response to the inflammatory
    challenge
    • Decreased tissue mass and formation of new
    tissue through granulation
    • Collagen and other molecules are synthesized
    • Formation of scar tissue
    • Remodeling process differs for various tissues
    Implant Factors

    • Bulk properties: chemical composition, structure,


    purity and presence of leachables.
    • Surface properties: smoothness, COF, geometry,
    hyrophilicity, surface charge
    • Mechanical properties: match properties of
    component being replaced, such as elastic
    modulus. Stability and fixation.
    • Long-term structural integrity: design for fatigue
    and fracture loading, wear, creep, and stress
    corrosion cracking
    Bioactivity spectra for bioceramics
    Reactivity of Ceramics

    • Bioinert- Pyrolytic carbon (heart valves),


    Alumina/Zirconia (orthopedic femoral heads)
    • Biodegradable- Calcium phosphate (artificial
    bone), tricalcium phosphate (peridontal defect
    repair)
    • Bioactive-glass ceramics (coatings pf
    orthopedic devices, bone plates).
    Host can affect the implant

    • Physically
    • Abrasive, adhesive, delamination wear
    • Fatigue and Fracture
    • Stress Corrosion cracking
    • General corrosion
    • Biologically
    • Absorption of substances from the tissues
    • Enzymatic degradation
    • Calcification
    Implant reactions in the body
    Host Factors

    • Age and health status


    • Immunological/metabolic status
    • Choice of surgeon: minimize tissue
    damage and contamination, proper
    implantation
    Biocompatibility testing

    • Cell toxicity
    • Thromobogenecity
    • Inflammatory response
    • Animal tests
    • Clinical trials
    • FDA regulations
    • ASTM/ISO standards
    Device sterility

    • Minimizes bacterial contamination


    • Reduces likelihood for infection
    • Can alter the material surface and bulk
    structure
    Design Issues

    • Shelf Aging-- Post Sterilization --Manufacturing


    issues-- what is the best sterilization method?
    What is shelf life for the device?
    Pre-Surgical Implant Life
    medical grade UHMWPE resin

    compression molded extruded direct compression molded

    “blocks” of UHMWPE rod of UHMWPE


    machined

    component

    sterilization

    shelf aging

    implanted
    STERILIZATION

    • One of the greatest challenges for devices is


    ensuring sterility
    • Many in-vivo degradation schemes have been
    linked to loss of mechanical properties due to
    post-sterilization aging
    Sterilization

    Sterility Definition: the state in which the


    probability of any one bacterial endospore
    -6
    surviving is 10 or lower

    Common Method: 25 kGy of 60Co gamma


    radiation in air
    STERILIZATION SCHEMES

    • Eto Gas
    • Steam
    • Autoclaving
    • E-beam radiation
    • Gamma Radiation*
    Gamma Radiation

    • Advantages:
    • deeply penetrating
    • no residuals
    • no post-sterilization treatment
    • crosslinking- good for wear resistance

    • Disadvantages:
    • chain cleavage, loss of molecular weight and higher crystallinity
    • embrittlement
    Oxygen aids in high reactivity towards free radical
    generation in radiation sterilization schemes

    • R -- --> R.} initiation


    • R. --O2--> RO2. } propagation
    • RO2. --RH-> RO2H + R. }
    • RO2H --RH-> RO. + . OH } chain branching
    • RO. --RH-> ROH + R. }
    • .OH --RH-> H O + R.
    2

    • RO2H, RO2., R. -----> scission and crosslinking


    • 2RO2. ----> RO2R + O2} termination
    Structural changes due to gamma
    sterilization and aging in UHMWPE

    • Increased crystallinity and density


    • Increased oxidation levels
    • Loss of fatigue and fracture properties
    DSC: Crystallinity

    60

    50
    Sterile Material has
    40 greater crystallinity after
    five years
    30
    % Crystallinity Implies chain scission

    20 in sterilized material

    10

    0
    Nonsterile Sterile
    Density evolution

    0.98
    Unsterilized n=18
    0.97
    Density (g/cc)

    Sterilized in N 2
    0.96 Sterilized in Air

    0.95

    0.94

    0.93
    0 1 2 3 4
    Aging Time (Weeks)
    TEM:microstructure evolution
    (aging)

    unaged aged
    Oxidation Model
    Sterilization affects fatigue resistance

    GUR4150HP unaged
    -3
    10
    d a /d N (m m /cy cle)

    -4
    10

    -5
    10
    G415Gi
    G415NS
    G415GA
    G415P
    G415Eto
    -6
    10
    1 2 3 4

    ²K (MPa¦m)
    Current Trends

    • Sterilization with EtO or Gas Plasma


    • Controlled crosslinking with ionizing schemes
    (Gamma inert, melt irradiated, E-beam--
    controlled crosslinking)
    Questions?

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