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    Biocompatibility: Biological Response Biocompatibility Tests Sterilization Issues

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    JASPREETKAUR0410
    Biological response and biocompatibility are important considerations for implantable materials. When a biomaterial is implanted in the body, it triggers an inflammatory response and biological interactions with tissues. A new biomaterial must undergo biocompatibility testing prior to implantation according to FDA regulations. The body's response to implantation involves acute and chronic inflammation, granulation tissue formation, foreign body reaction, and fibrosis or encapsulation of the implant. Surface properties, bulk properties, and host factors all influence biocompatibility.

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    Biocompatibility: Biological Response Biocompatibility Tests Sterilization Issues

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    JASPREETKAUR0410
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    Biological response and biocompatibility are important considerations for implantable materials. When a biomaterial is implanted in the body, it triggers an inflammatory response and biological interactions with tissues. A new biomaterial must undergo biocompatibility testing prior to implantation according to FDA regulations. The body's response to implantation involves acute and chronic inflammation, granulation tissue formation, foreign body reaction, and fibrosis or encapsulation of the implant. Surface properties, bulk properties, and host factors all influence biocompatibility.

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    Bio Compa Tibi Lty

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    Bio Compa Tibi Lty

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    Biological response and biocompatibility are important considerations for implantable materials. When a biomaterial is implanted in the body, it triggers an inflammatory response and biological interactions with tissues. A new biomaterial must undergo biocompatibility testing prior to implantation according to FDA regulations. The body's response to implantation involves acute and chronic inflammation, granulation tissue formation, foreign body reaction, and fibrosis or encapsulation of the implant. Surface properties, bulk properties, and host factors all influence biocompatibility.

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

    Biocompatibility: Biological Response Biocompatibility Tests Sterilization Issues

    Uploaded by

    JASPREETKAUR0410
    Biological response and biocompatibility are important considerations for implantable materials. When a biomaterial is implanted in the body, it triggers an inflammatory response and biological interactions with tissues. A new biomaterial must undergo biocompatibility testing prior to implantation according to FDA regulations. The body's response to implantation involves acute and chronic inflammation, granulation tissue formation, foreign body reaction, and fibrosis or encapsulation of the implant. Surface properties, bulk properties, and host factors all influence biocompatibility.

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    of 41

    Biocompatibility

    Biological response Biocompatibility tests Sterilization Issues

    Biocompatibility
    Arises from differences between living and nonliving 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) Marieb, EN and Mallatt, J. 1997. Human Monocytes macrophages Anatomy (months)

    Acute Inflammation
    Short term (minutesdays) 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 presentimmunoglobin 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 occurthis 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 reactionsmediate antibody production. Macrophages process and deliver antigen to immunocompetent cells mediate immune reactions.

    www.lumen.com

    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 35 days of implantation of a biomaterialit 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 surviving is 10 -6or lower
    Common

    Method: 25 kGy of radiation in air

    60

    Co gamma

    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 --g --> 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

    40 % Crystallinity 30 20 10 0 Nonsterile Sterile

    Material has greater crystallinity after five years


    Implies

    chain scission in sterilized material

    Density evolution
    0.98 0.97 0.96 0.95 0.94 0.93 0 1 2 3 Aging Time (Weeks) 4 Unsterilized Sterilized in N 2 Sterilized in Air n=18

    Density (g/cc)

    TEM:microstructure evolution (aging)

    unaged

    aged

    Oxidation Model

    Sterilization affects fatigue resistance

    GUR4 150HP unage d 10


    -3

    da/dN (mm/cycle)

    10

    -4

    10

    -5

    G415Gi G415NS G415GA G415P G415Eto


    -6

    10

    2 K (M Pam)

    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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