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Medical biomaterials - Coggle Diagram

- - - - external source: atmospheric contamination
      - internal sources:
        
        human
        
        proportion of human contamination in clean room working is 80%
        
        people shed skin and other particles including microbes constantly
        
        machines and devices
        
        processing
        
        chemicals and gases
        
        bacteria
    - - Construction:
        
        standards
        
        layout
        
        ventilation
        
        turbulent flow clean room
        
        laminar flow clean room
        
        HEPA and ULPA filters
        
        localized clean areas, biosafety isolators, separate rooms, air showers, door interlocks, airlocks
        
        "Onion" concept: cleanest areas are inside
        
        modularized structure: if one area is contaminated, not all are
        
        construction materials
        
        services
        
        setting clean room to work
      - Testing:
        
        performance after construction
        
        particle contamination is determined in different conditions:
        
        as built
        
        at rest
        
        in operation
        
        continuation of performance
        
        air quality must be monitored continuously
        
        microbiological follow-up:
        
        contamination can be studied in many ways:
        
        centrifugal sampler for active air sampling
        
        settle plate method
        
        contact plate method
        
        swabbing
        
        alert limit and action limit
        
        amount of the microbes is usually reported as colony forming unit / dish
        
        follow-up must be done for long periods at a time
      - Operations:
        
        monitoring conditions
        
        monitoring the entry of people, machines and materials
        
        inspection of packages and materials in case of tearing
        
        disinfection of materials at both sides of the airlock
        
        materials:
        
        floors, walls and ceilings are smooth, water-resistant and chemically resistant
        
        doors are air locks or air showers
        
        chairs are ergonomic and cleanable
        
        cupboards as storage
        
        transfer of goods is via a two way hatch system
        
        what to avoid:
        
        shelves
        
        window ledges
        
        door frames
        
        water sources
        
        clean room disclipines
        
        elimination of cross contamination: products are moving into only one direction
        
        accurate and relevant working (requires education)
        
        slow and preplanned movement
        
        good all-around hygiene
        
        regular and relevant cleaning, tidiness
        
        garments
        
        clean room clothes reduces the movement of particles in the air
        
        GGP = good gowning practice
        
        cleaning and equipment
  - - - microelectronic industry
      - solid-state (electronic) industry
      - micromechanical industry
      - optical industry
    - - biotechnological industry
      - medical industry
      - medical functions
      - manufacturing of medical materials and devices
    - - food industry
  - - - compare with:
        
        disinfection = destroying living pathogens, but not all spores
        
        cleaning = lowering the number of pathogens on the surface (essential step for successful disinfection and sterilization
        
        antiseptic = substance that inhibits microbial activity/prevents growth
        
        aseptic = free of OR using methods to keep free of micro-organisms, aiming to achieve a germ-free condition
      - required for all implantable biomaterials
      - Classifications of the CDC (centers for disease control and prevention)
        
        critical devices:
        
        materials/instruments that are going to be in contact with tissues, blood or blood vessels
        
        surgical instruments, cardiac and urinary catheters, implants and ultrasound probes
        
        semi critical devices:
        
        items that come in contact with mucous membranes or non-intact skin
        
        respiratory therapy and anesthesia equipment, some endoscopes, laryngoscope blades
        
        non-critical devices:
        
        items that come in contact with intact skin but not mucous membranes
        
        bedpans, blood pressure cuffs, crutches, bed rails, linens, bedside tables, patient furniture, floors
    - - probability of a single product unit being non-sterile after sterilization
      - SAL for each device depends on the intended use and regulatory
        requirements
      - producer or distributor must provide evidence about the validation of sterilization process
    - - = degree of microbial contamination or microbial load
      - aka the number of micro-organisms contaminating an object
      - you need to know the number and type of microbes before selecting an appropriate sterilization method and parameters
    - - = time for which the quality of the device is stable and the device remains sterile
      - after shelf life:
        
        might be safe, but not quaranteed
        
        use is forbidden
      - determines and validated the appropriate storage conditions and expiration dates
      - accelerated shelf life testing, then real time shelf life testing
    - - Steam (autoclave)
        
        simple, effective, low cost, fast, nontoxic, relatively low temps
        
        -> widely used
        
        moist heat denaturizes proteins (coagulation) and dissolves the cell membranes
        
        suitable for liquids, most metals, glass and some plastics, but also liquids
        
        efficiency is dependent
        
        temperature
        
        time
        
        water presence
        
        disadvantages:
        
        risk of burns
        
        use of elevated temperatures compared to other methods
        
        possible deposition of impurities present in the steam
        
        not suitable for many synthetic and natural materials
        
        deleterious for heat-sensitive instruments
        
        microsurgical instruments can't handle repeated exposure
        
        may leave wetness -> rust
      - Ethylene oxide (EtO)
        
        colorless liquid that boils in 10 C
        
        process:
        
        pre-conditions
        
        thw product is exposed to a warm, humid environment for at least 12h to ensure uniform temp and humidity
        
        exposure
        
        vacuum is pulled and EtO gas is introduced, exposure for 4-8h
        
        post-conditions
        
        EtO gas is removed by repeatedly pulling a vacuum and introducing air, 8-12h
        
        simple, efficient at low temps (40-50C), penetrates well, compatible with materials (electronics)
        
        disadvantages:
        
        irritation: skin, conjuctiva and nasal mucosa
        
        EtO is toxic, carcinogenic, mutagenic and flammable
        
        requires aeration time to remove residue
        
        takes a long time
        
        storing requires special accomodations
        
        can react with biomaterials' surface
        
        some materials cannot handle the humidity
      - Irradiation sterilization
        
        most common
- - - - = latin, in glass
      - something (cells, biomaterials etc) is studied outside of the typical biological contexts, in a lab environment (highly controlled)
      - good for controlling variables and initial testing
      - Cell cultures
        
        valuable information about biocompatibility, cell attachment, growth and activity etc
        
        limitations:
        
        absence of some signalling
        
        diffusion of nutrients and waste products are not great
        
        no mechanical strain
        
        2D
      - New tech
        
        organ-on-chip
        
        body-on-chip
        
        decreased need for animal testing?
    - - = latin, within the living
      - tests are done in living organisms, usually animals (incl. humans)
      - good for representing real environments and 3D-studies
    - - intended patient contact
      - duration of contact
    - - SFS online
      - registrations and approval take time and money
        
        often better to use approved materials!!
- - - - Stiffness
        
        = no deformation (elastic or plastic), high elastic modulus
      - Toughness
        
        = ability to absorb energy before failure (depends on strength and strain)
      - Strength
        
        = materials ability to withstand applied load (before plastic deformation = yield strength, before failure = ultimate strength, may others)
      - Ductility
        
        = lots of plastic deformation before failure
      - Brittleness
        
        = failure without plastic deformation
      - Hardness
        
        = resistance to plastic deformation, e.g. resistance to scratches
    - - Point of fracture (end of curve) and tensile strength (peak of curve)
      - linear region is elastic deformation and is used to calculate modulus of elasticity (=stiffness), after that plastic deformation starts
    - - 5 main ones:
        
        compression (pushing along the axis)
        
        tension (pulling along the axis)
        
        shear (pulling perpendicular to the axis)
        
        torsion (turning the axis in opposite directions)
        
        bending (i think you can figure this one out)
      - Example: bone
        
        relatively hard
        
        anisotropic mechanical properties
        
        = properties depend on direction of loading
        
        weakest in shear, strongest in compression
        
        viscoelastic
        
        = stress-strain behavior depends on rate of applied strain (has a weird stress-strain curve)
  - - - bone fracture/trauma operations (screws, plates...)
      - Knee and ankle operations (also screws, plates...)
      - Face/head/CMF surgery (also screws and plates...)
      - Hip and other total prosthesis
      - Instruments (needles, drills, scalpels...)
      - Stents (urologic, gastroenterologic and vascular)
      - Dentistry (fillings, bridges, arcs, implants...)
    - - Stainless steels
      - Titanium and titanium-based alloys
      - Cobalt alloys
    - - Biocompatibility
        
        Electrochemical interactions may lead to oxidization and extraction of metal ions (=corrosion)
        
        biocompatibility is determined by the potentially toxic effect of these ions to the tissue
        
        better corrosion resistance => often better biocompatibility
        
        Tissue fluids are corrosive (normal pH ~7, infection etc can decrease it to 4-5)
        
        if ion concentration in surroundings increases, ions can enter cell
        
        too many ions in cell -> cytotoxicity
        
        Note! cells can tolerate ions already familiar to them
        
        Overall corrosion must be in control for biocompatibility!!!
        
        :!:Passive oxide layer
        
        result or oxidization (oxygen from body, metal ions from implant), forms on the surface of some metals
        
        important protection against the corrosive environment
        
        oxide layer is usually nearly inert
        
        prevents future reactions
        
        formed by e.g.
        
        Fe-Cr-Ni
        
        Co-Cr-Mo
        
        Mg-Al
        
        Ag-Sn
        
        Cu-Sn
        
        :!:Corrosion
        
        Different types (may occur simultaneously):
        
        Pitting corrosion
        
        = local weak points are exposed -> oxide layer fails
        
        point is formed and acts as an anode, surroundings as cathode => deep pits are created
        
        caused by several factors (metal impurities, failed heat treatment, surrounding pH and/or anion concentration)
        
        Fretting corrosion
        
        oxide layer worn off by mechanical action
        
        Crevice corrotion
        
        = anode-cathode reaction of whole surface, difference in geometry becomes an anode
        
        rapid progression due to fast pH drop in cavity
        
        Intergranular corrosion
        
        = occurs mostly along grain boundaries for some alloys in specific environments
        
        Stress corrosion (cracking)
        
        = stress + corrosion (neither one alone)
        
        can occur at relatively low stress
        
        Galvanic corrosion
        
        two metals in a electrical contact, less noble metal corrodes (galvanic cell)
        
        Important to know physical and chemical properties!!!
      - Manufacturing
        
        Easily processed into complex shapes
        
        Easy to clean and sterilize again and again
      - Long history and reasonable costs
        
        properties are well known
        
        availability is good
        
        relatively cheap
      - Electrical and thermal conductivity
        
        excellent at both
        
        can be used in electronic devices (e.g. pacemaker electrodes)
      - Mechanical properties
        
        better than ceramics and polymers in tensile and fatigue strength, and fracture toughness
    - - Corrosion!!!
      - Wear
        
        Metal parts are usually in contact with others
        
        friction causes surfaces to wear
        
        particles enter surrounding tissue (results same as corrosion)
        
        implant loosening can cause new trauma
      - Fatigue breakdown
        
        cyclic loading (typical of the body) can cause breakage
      - Stress shielding
        
        = "if you don't use, you'll lose it!"
        
        may be caused by mismatch of mechanical properties of implant and bone
        
        if metal takes greater part of weight load, implant is overloaded and bone unloaded and bone resorption / osteoporosis follows
- - - - What happens?
        
        To the material
        
        Degredation
        
        Inertness
        
        Positive chemical reaction
        
        To the sorrounding tissue
        
        Negative reaction
        
        Harmful FBR
        
        Leads to implant failure -> should always be avoided
        
        For example:
        
        Allergy
        
        :!:Toxicity
        
        :!:Cytotoxicity
        
        1 more item...
        
        = material that releases some harmful substances in sufficient quantities to kill cells either directly or indirectly
        
        Genotoxicity
        
        1 more item...
        
        Cell death
        
        Tissue necrosis
        
        :!:Infection
        
        Sterility is very important!!
        
        Usually a normal part of would healing (secondary barrier)
        
        The body may try to get rid of foreign body by infection and pushing the implant out
        
        Neutral (nearly inert) reaction
        
        Acceptable, neither an advantage nor a disadvantage
        
        "Inert" is never completely true, but nearly inert can be
        
        Most common response:
        
        :!:Non-adherent fibrous capsule
        
        Isolating the implant from the host tissue
        
        Interface is not chemically or biologically bonded
        
        1 more item...
        
        What happens?
        
        2 more items...
        
        Positive
        
        Adventageous to body
        
        This should be the aim
        
        :!:Bioactive reaction
        
        :!:Bioactive material
        
        Specific biological response at surface
        
        2 more items...
        
        controlled rate of chemical reactivity
        
        Does not necessarily dissolve entirely (comp. resorbable implants)
        
        Two types of bioactivities (different rates and mechanisms)
        
        2 more items...
        
        :!:Bioabsorbable implant
        
        material is degraded or dissolved and
        
        degredation products are removed via normal metabolic routes
        
        No stance on what happens to the degredation products
        
        Implant gradually disappears, gets replaced by tissue
        
        Tissue repair
        
        Steps:
        
        Inflammation
        
        Cells of the body explore the new absorbed proteins on the surface and may bind to them (minutes to hours)
        
        What if bacteria adhere to the surface?
        
        3 more items...
        
        These cells determine the fate of the implant!!!
        
        =/= infection
        
        in infection, there are always micro-organisms present
        
        inflammation can be caused by infection
        
        normal part of body's immune response (second line of defence)
        
        Symptoms:
        
        Heat (increased blood flow)
        
        Redness
        
        Pain
        
        Swelling
        
        Classification:
        
        :!:Acute inflammation
        
        5 more items...
        
        :!:Chronic inflammation
        
        4 more items...
        
        Hemostasis
        
        Water molecules adhere to the surface (in nanoseconds)
        
        Layer of proteins is formed from body fluids (from ms to minutes)
        
        = Bleeding stops
        
        platelet plug forms
        
        fibrinogen polymerization to fibrin -> coagulation
        
        Proliferation
        
        = growth, increasement
        
        characterized by anglogenesis (= new blood vessel formation) and collagen deposition
        
        Remodeling
        
        = "reorganization" in the tissue to provide grater tensile strength
        
        mechanical properties improve towards the pre-injury ones
    - - Surface properties =/= bulk properties
        
        Bulk properties cannot be a determination for the behavior of cells or tissues
        
        Surface properties can depend on the environment (air or water etc)
    - - = material, that has been designed to interface with biological systems for the treatment, augmentation or replacement of biological functions (google)
      - material <-> host interactions