Biomaterials

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Biomaterials by Mind Map: Biomaterials

1. Surface Characteristics

1.1. Non-Fouling Surfaces

1.1.1. Resist protein adsorption/cell adhesion

1.1.1.1. Generally, surfaces that strongly adsorb proteins, bind to cells

1.1.2. Used in areas in contact with bacteria and blood in vivo (implants) and in vitro (diagnostics, sensors)

1.1.3. Important in devices that may inhibit bacterial colonization and blood cell adhesion

1.1.4. polyethylene glycol (PEG)- most common

1.1.4.1. Highly hydrophillic material surface

1.1.4.2. Polymer coils become surrounded by water- takes energy to compress and remove

1.1.4.3. may undergo oxidative damage in vivo- not stable long term

1.1.4.4. FDA approved

1.2. Hydrophobic Surfaces

1.2.1. Adosrb a protein monolayer

1.3. Hydrophillic Surfaces

1.3.1. Resist Protein Adsorption

1.3.2. Forms "water shell"- favorable to replace surrounding water with proteins/cells

2. Biofilms

2.1. Issue in transcutaneous implants, but also for full implants

2.2. Slime -- Extracellular Polymeric Substance (EPS)

2.3. Stimulate significant inflammatory reaction

2.3.1. Degrading host tissue-- feeding bacteria

2.3.2. Usually isolated to material surface but can be septic in chronic cases

2.4. Structural protection

2.4.1. Resists phagocytosis and antibiotics

2.4.2. More resistant to environmental stresses

2.5. If the conditioning film is stopped- biofilm is stopped

2.6. Adhere to both hydrophobic & hydrophilic surfaces

2.7. Adhere to both smooth & rough surfaces

2.7.1. Textured surfaces in transcutaneous implants to promote high tissue integration

2.8. More common in fluid management systems than orthopedic implants

2.9. Detection

2.9.1. Sonication

2.9.2. Culture of slime strains

2.9.3. Microscopy (definitive)

2.9.4. CANNOT use MRI or CT for non-invasive detection

2.10. Prevention

2.10.1. Better sterility protocols

2.10.2. Non-adhesive bactericidal coatings

2.10.3. Items such as antibiotic bone cement in surgery

3. Entropy & Enthalpy

3.1. Entropy

3.1.1. Measure of disorder or randomness

3.1.2. Entropy increases over time

3.2. Enthalpy

3.2.1. Total kinetic & potential energy of a system at constant pressure

3.2.2. Change in enthalpy = Change in heat of a system

3.3. Adsorption Factors

3.3.1. Entropic gain of released water

3.3.2. Enthalpy loss due to cation/anion interactions between ionic protein and surface groups

3.4. Factors resisting adsorption

3.4.1. Retention of bound water, entropic and osmotic repulsion of polymer coils

4. Biological Materials

4.1. Hard tissue (Bone)

4.2. Soft Tissue (Blood vessels)

4.3. Blood

4.3.1. Improve blood compatibility

4.3.1.1. Reduce fibrinogen adsorption (required for platelet adhesion)

4.3.1.2. PEO coatings reduce fibrinogen and platelet adhesion

4.3.2. Components

4.3.2.1. Plasma

4.3.2.1.1. No cells-- water, salts, and proteins

4.3.2.2. Leukocytes

4.3.2.3. Erythrocytes

4.3.2.4. Platelets

4.3.2.4.1. Fragments of large megakaryocytes

4.3.2.4.2. Purpose is to coagulate when activated-- forming a blood clot

4.3.2.4.3. Likely to bind to absorbed proteins

4.3.2.4.4. Structure

4.3.2.4.5. May be removed faster in chronic thrombosis

4.4. Protein

4.4.1. Affinity

4.4.1.1. Proteins adsorb onto hydrophobic surfaces

4.4.1.2. Ionic attraction- anionic/cationic

4.4.1.3. Proteins adsorb into monolayers- fill any open space

4.4.2. Structure

4.4.2.1. Primary Structure

4.4.2.1.1. Amino Acid Sequence

4.4.2.2. Secondary Structure

4.4.2.2.1. Alpha helix or Beta pleated sheets

4.4.2.3. Tertiary Structure

4.4.2.3.1. 3D shape with max stability and lowest energy state

4.4.2.4. Quaternary Structure

4.4.2.4.1. Protein subunit, may be repeated

4.4.3. Conformational/Biological Changes

4.4.3.1. Soft Proteins

4.4.3.1.1. More conformative-- less stable

4.4.3.2. Hard Proteins

4.4.3.2.1. Less conformative-- more stable

4.4.3.2.2. Competition in adsorption

4.4.4. Monolayer adsorption

4.4.5. Factors affecting protein adsorption

4.4.5.1. Intrinsic Surface Activity

4.4.5.2. Bulk concentration of protein

4.4.5.3. Effect of different surfaces on selective adsorption/biological activity of adsorbed protein

5. Complications

5.1. Systemic Effects

5.1.1. Toxicity

5.1.2. Hypersensitivity

5.2. Corrosion

5.2.1. In metals

5.3. Calcification

5.3.1. Synthetic and biological materials

5.3.1.1. Cardiac valves, pumps, breast implants, urological stents, intraocular lenses, etc.

5.4. Blood-Material Interactions

5.4.1. Thrombosis

5.4.1.1. Difficult to make materials thromboresistant

5.4.2. Embolization

5.4.3. Consumption of platelets and plasma coagulation factors, platelet activation and systemic effects

5.4.4. Surface thrombogenecity, hypercoagulability, locally static blood flow

5.4.5. Platelet adhesion

5.4.6. Anticoagulants (warfarin) prevent fibrin clots but not platelet activation

5.5. Tumor formation

5.5.1. Rare-- not well understood

5.6. Infection

5.6.1. 5-10% of implant patients -- major source of morbidity/mortality

5.6.2. Often resistant to antibiotics -- Remove device

5.6.3. Early infections (1-2 months) from poor sterility during operation.

5.6.4. Urinary catheters are a major source

6. Testing

6.1. Sterilization

6.1.1. 3 methods

6.1.1.1. Steam (Autoclave) Sterilization

6.1.1.1.1. Reusable devices in hospitals

6.1.1.1.2. High temps limit use for most devices with plastic and many single-use devices

6.1.1.2. Radiation Sterilization

6.1.1.2.1. Sterilized inside final packaging

6.1.1.2.2. Breaks DNA to eliminate microbes

6.1.1.2.3. Takes minutes to ~12 hours

6.1.1.2.4. Secondary electrons may influence material

6.1.1.2.5. Lethal level of radiation-- shielding/ventilation needed

6.1.1.2.6. Most materials inert to radiation

6.1.1.3. Ethylene Oxide (EO) Sterilization

6.1.1.3.1. Toxic, carcinogenic, explosive gas

6.1.1.3.2. Must aerate after sterilization

6.1.1.3.3. Fully packaged during sterilization

6.1.1.3.4. Uses humidity, EO gas, temperature, vacuum conditions

6.1.1.3.5. 6 hours to several days

6.1.1.3.6. Temperature, humidity, and evacuation cycles can affect material

6.1.1.3.7. Bioabsorbable polymers do not do well -- structural integrity, early degradation

6.1.2. Material compatibility

6.2. Biological Testing

6.2.1. In vivo

6.2.1.1. Biocompatible Biomaterial

6.2.1.1.1. Mild inflammatory reaction

6.2.1.1.2. Thin fibrous capsule after 2-3 weeks

6.2.1.1.3. FBGCs typically indicate poor biocompatiblity and FBR

6.2.1.2. 4 factors:

6.2.1.2.1. Toxicology

6.2.1.2.2. Extrinsic organisms

6.2.1.2.3. Mechanical Effects

6.2.1.2.4. Cell-biomaterial interactions

6.2.2. In vitro

6.2.2.1. Toxicant -- Chemicals that are potentially harmful and depend on:

6.2.2.1.1. Factors

6.2.2.1.2. Toxicology Risk Assessment

6.2.2.1.3. Tolerable Intakes (TI)

6.2.2.1.4. Genotoxicity

6.2.2.1.5. Cytotoxicity

7. Materials

7.1. Hydrogels

7.1.1. Basic Structures

7.1.1.1. Homopolymer Hydrogels

7.1.1.2. Copolymer Hydrogels

7.1.1.3. Multi-polymer Hydrogels

7.1.1.4. Interpenetrating Networks (IPN) Hydrogels

7.1.1.5. Ideal networks are rare

7.1.2. Ionic Hydrogels

7.1.2.1. Neutral

7.1.2.2. Anionic

7.1.2.3. Cationic

7.1.2.4. Ampholytic

7.1.3. Physiochemical Structure

7.1.3.1. Amorphous

7.1.3.2. Semicrystalline

7.1.4. Stability

7.1.4.1. Degradability

7.1.4.2. Hydrophilicity/Hydrophobicity

7.2. Degradable/Resorbable Materials

7.2.1. Degradation

7.2.1.1. Chemical process resulting in cleavage of covalent bonds

7.2.1.2. Hydrolysis is the most common process in polymers

7.2.2. Biodegrdation

7.2.2.1. Specific to biological agents (enzymes, cells, microorganisms)

7.2.2.2. EXAMPLE: PLA backbone broken down by hydrolysis -- NOT biodegradation

7.2.2.3. All polymers undergo some degree of degradation

7.2.2.4. Minutes to years

7.2.2.4.1. material can become soluble, rubbery, rigid, brittle

7.2.2.4.2. Calcification -- good for bones, cracking in polymers

7.2.2.5. Hydrolysis

7.2.2.5.1. Hydrophobic, cross-linking, high crystallinity polymers unlikely to be degraded by hydrolysis

7.2.2.5.2. Polyether urethane resistant to hydrolysis in vivo

7.2.2.6. Oxidation

7.2.2.6.1. hydrophobic polymers with crystallinity also resist oxidation

7.2.2.6.2. Oxidative-suceptible functional groups

7.2.3. Erosion

7.2.3.1. Physical changes in size, shape, and mass

7.2.3.2. Due to degradation, dissolution, ablation, mechanical wear

7.2.4. Bioerosion

7.2.4.1. Bulk

7.2.4.1.1. Water-insoluble polymer converted in the body into water-soluble material

7.2.4.2. Surface

7.2.4.2.1. Degrades outside surface-- water cannot enter material interior

7.2.5. Bioresorption/Bioadsorption

7.2.5.1. Degradation products (polymers) removed by cellular activity (ex. phagocytosis)

7.2.6. Applications

7.2.6.1. Temporary Implants and drug delivery systems