POLYMERIC IMPLANTS Biodegradable suture Wound dressing Intraocular Lens Contact Lens

Some Commonly Used Polymers Material Applications Silicone rubber Catheters, tubing Dacron Vascular grafts Cellulose Dialysis membranes Poly(methyl methacrylate) Intraocular lenses, bone cement Polyurethanes Catheters, pacemaker leads Hydogels Opthalmological devices, Drug Delivery Collagen (reprocessed) Opthalmologic applications, wound dressings

Polymer Devices Advantages: Disadvantages: Examples: Some joint replacement articulating surfaces Spinal cages Biodegradable bone plates for low load regions Biodegradable sutures See Table 1.1 of Park Hip joint Spinal cage for spine fusion Bone plates

Mechanical Properties: Why is important to study for all biomaterials? Determines how well it will work (or not work) for a given device. One major factor is the modulus of the material. metal polymer polymer Toe implant ______________ hydrogel ____________

Polymers Terminology: copolymer: polymers of two mer types random · · ·-B-A-B-A-B-B-A-· · · alternating· · ·-A-B-A-B-A-B-A-· · · block · · ·-A-A-A-A-B-B-B-· · · heteropolymer: polymers of many mer types COPOLYMER

Polymers Structure Linear Branched Crosslinked

Synthetic Polymers Biostable Polymers Biodegradable Synthetic Polymers Polyamides Polyurethanes Polyethylene Poly(vinylchloride) Poly(hydroxyethylmethacrylate) Poly(methylmethacrylate) Poly(tetrafluoroethylene) Poly(dimethyl siloxane) Poly(vinylalcohol) Poly(ethylenglycol) Biodegradable Synthetic Polymers Poly(alkylene ester)s PLA, PCL, PLGA Poly(aromatic/aliphatic ester)s Poly(amide-ester)s Poly(ester-urethane)s Polyanhydrides Polyphosphazenes Stimuli Responsive Poly(ethylene oxide-co-propilene oxide) Poly(methylvinylether) Poly(N-alkyl acrylamide)s Poly(phosphazone)s

Polymers Bioinert Biodegradable Polymers Natural Synthetic

Synthetic Biomaterials POLYMERS: Silicones, Gore-tex (ePTFE), Polyethylenes (LDPE,HDPE,UHMWPE,) Polyurethanes, Polymethylmethacrylate, Polysulfone, Delrin Uses: Orthopedics, artificial tendons, catheters, vascular grafts, facial and soft tissue reconstruction COMPOSITES: CFRC, self reinforced, hybrids Uses: Orthopedics, scaffolds HYDROGELS: Cellulose, Acrylic co-polymers Uses: Drug delivery, vitreous implants, wound healing RESORBABLES: Polyglycolic Acid, Polylactic acid, polyesters Uses: sutures, drug delivery, in-growth, tissue engineering

Polymers: Biomedical Applications Polyethylene (PE) five density grades: ultrahigh, high, low, linear low and very low density UHMWPE and HDPE more crystalline UHMWPE has better mechanical properties, stability and lower cost UHMWPE can be sterilized (C2H4)nH2

Polymers: Biomedical Applications UHMWPE: Acetabular caps in hip implants and patellar surface of knee joints. HDPE used as pharmaceutical bottles, fabrics. Others used as bags, pouches, tubes etc.

Artificial Hip Joints (UHMWPE) http://www.totaljoints.info/Hip.jpg

Polymers: Biomedical Applications Polymethylmethacrylate (PMMA, lucite, acrylic, plexiglas) (C5O2H8)n acrylics transparency tough biocompatible Used in dental restorations, membrane for dialysis, ocular lenses, contact lenses, bone cements

Intraocular Lens 3 basic materials - PMMA, acrylic, silicone

Polymers: Biomedical Applications Polyamides (PA, nylon) PA 6 : [NH−(CH2)5−CO]n made from ε-Caprolactam high degree of crystallinity interchain hydrogen bonds provide superior mechanical strength (Kevlar fibers stronger than metals) plasticized by water, not good in physiological environment Used as sutures

Polymers: Biomedical Applications Polyvinylchloride (PVC) (monomer residue must be very low) Cl side chains amorphous, hard and brittle due to Cl metallic additives prevent thermal degradation Used as blood and solution bags, packaging, IV sets, dialysis devices, catheter, bottles, cannulae

Polymers: Biomedical Applications Polypropylene (PP) (C3H6)n properties similar to HDPE good fatigue resistance Used as syringes, oxygenator membranes, sutures, fabrics, vascular grafts Polyesters (polymers which contain the ester functional group in their main chain) PET (C10H8O4)n hydrophobic (beverage container PET) molded into complex shapes Used as vascular grafts, sutures, heart valves, catheter housings

Polymers: Biomedical Applications Polytetrafluoroethylene (PTFE, teflon) (C2F4)n low coefficient of friction (low interfacial forces between its surface and another material) very low surface energy high crystallinity low modulus and strength difficult to process catheters, artificial vascular grafts

Polymers: Biomedical Applications Polyurethanes block copolymer structure good mechanical properties good biocompatibility tubing, vascular grafts, pacemaker lead insulation, heart assist balloon pumps

Polyurethanes A urethane has an ester group and amide group bonded to the same carbon. Urethanes can be prepare by treating an isocyanate with an alcohol. Polyurethanes are polymers that contain urethane groups.

Synthetic vascular grafts from W.L.Gore Often the surgery will be 4 – 5 grafts, or as many as 9!! Synthetic not good for small diam. because they get clogged. Many people who need vascular grafts have pre-existing vascular conditions, can’t take another graft or not healthy, so need a substitute sdVG.

Useful Definitions Biodegradable Undergoes degradation in the body - Degradation products are harmless and can be secreted naturally water Lactic acid PLLA bone plates

Polymers: Biomedical Applications Rubbers latex, silicone good biocompatibility Used as maxillofacial prosthetics

Biomedical polymer Application Poly(ethylene) (PE) Low density (LDPE) High density (HDPE) Ultra high molecular weight (UHMWPE) Bags, tubing Nonwoven fabric, catheter   Orthopedic and facial implants Poly(methyl methacrylate) (PMMA) Intraocular lens, dentures, bone cement Poly(vinyl chloride) (PVC) Blood bags, catheters, cannulae Poly(ethylene terephthalate) (PET) Artificial vascular graft, sutures, heart valves Poly(esters) Bioresorbable sutures, surgical products, controlled drug release Poly(amides) (Nylons) Catheters, sutures Poly(urethanes) (PU) Coat implants, film, tubing Table The clinical uses of some of the most common biomedical polymers relate to their chemical structure and physical properties.

Hydrogels Water-swollen, crosslinked polymeric structure produced by reactions of monomers or by hydrogen bonding Hydrophilic polymers that can absorb up to thousands of times their dry weight in H2O Three-dimensional insoluble polymer networks

Applications of Hydrogels Soft contact lenses Pills/capsules Bioadhesive carriers Implant coatings Transdermal drug delivery Electrophoresis gels Wound healing Chromatographic packaging material

Types of Hydrogels Classification Method of preparation Ionic charge Homo-polymer, Copolymer, Multi-polymer, Interpenetrating polymeric Ionic charge Neutral, Catatonic, Anionic, Ampholytic Physical structure Amorphous, Semi-crystalline, Hydrogen-bonded

Types of Gelation Physical , Chemical ژله‌اي شدن فيزيكي: زنجيرهاي پليمر از طريق واكنش‌هاي يوني، پيوند هيدروژني، درهم گره خوردن مولكولي يا از راه طبيعت آب‌گريزي ماده اتصال مي‌يابند. ژله‌اي شدن شيميايي: زنجيرهاي هيدروژل با پيوند كووالانت به يكديگر متصل شده‌اند. در اين فرآيند، روش‌هايي نظير تابش، افزودن اتصال‌دهنده‌هاي عرضي شيميايي و تركيبات واكنش‌گر چند منظوره به كار مي‌روند.

Types of Hydrogels Natural Polymers Dextran, Chitosan, Collagen, Alginate, Dextran Sulfate, . . . Advantages Generally have high biocompatibility Intrinsic cellular interactions Biodegradable Cell controlled degradability Low toxicity byproducts Disadvantages Mechanical Strength Batch variation Animal derived materials may pass on viruses

Types of Hydrogels Synthetic Polymers PEG-PLA-PEG, Poly (vinyl alcohol) Advantages Precise control and mass produced Can be tailored to give a wide range of properties (can be designed to meet specific needs) Low immunogenecity Minimize risk of biological pathogens or contaminants Disadvantages Low biodegradability Can include toxic substances Combination of natural and synthetic Collagen-acrylate, P (PEG-co-peptides)

Properties of Hydrogels Swelling properties influenced by changes in the environment pH, temperature, ionic strength, solvent composition, pressure, and electrical potential Can be biodegradable, bioerodible, and bioabsorbable Can degrade in controlled fashion

Properties of Hydrogels Pore Size Fabrication techniques Shape and surface/volume ratio H2O content Strength Swelling activation

Advantages of Hydrogels Environment can protect cells and other substances (i.e. drugs, proteins, and peptides) Timed release of growth factors and other nutrients to ensure proper tissue growth Good transport properties Biocompatible Can be injected Easy to modify

Disadvantages of Hydrogels Low mechanical strength Hard to handle Difficult to load Sterilization

Why Hydrogels ?: Tissue Engineering Biocompatible H2O content Sterilizibilty Ease of use High mechanical Strength Surface to volume ratio Good cell adhesion High nutrient transport

Why Hydrogels?: Cell Culture Systems Biocompatible substrate Non-toxic and have no immunological responses Cytoarchitecture which favors cell growth Flexibility for cells to rearrange in 3-D orientation Seeded with appropriate growth and adhesion factors Porosity (i.e. channels for nutrients to be delivered)

Why Hydrogels?: Cell Culture Systems Mimic cytomechanical situations 3-D space provides balanced cytoskeleton forces Dynamic loading to promote cell growth Flexibility Provide scaffold for various cells Consistent, reproducible and easy to construct

Why Hydrogels?: Drug Delivery Safe degradation products Biocompatible High loading with ensured molecule efficacy High encapsulation Variable release profile Stable Inexpensive High quality

Environment controls mechanisms of swelling: Hydrogels are network polymers that swell through a variety of mechanisms in an aqueous environment Environment controls mechanisms of swelling: pH, ionic strength, solvent composition, pressure and even electric fields Applications in medicine, engineering, and biology

Chitosan Chitosan (2-amino-2deoxy-(1→4)-β-D-glucopyranan), a polyaminosaccharide, obtained by alkaline deacetylation of chitin (the principal component of living organisms such as fungi and crustacea).

Chitosan’s key properties: 1) biocompatibility 2) nonantigenicity 3) nontoxicity (its degradation products are known natural metabolites) 4) the ability to improve wound healing/or clot blood 5) the ability to absorb liquids and to form protective films and coatings, and 6) selective binding of acidic liquids, thereby lowering serum cholesterol levels.

Alginate Guluronic acid Mannuronic acid These products are produced from naturally occurring calcium and sodium salts of alginic acid found in a family of brown seaweed. Alginates are rich in either mannuronic acid or guluronic acid, the relative amount of each influence the amount of exudate absorbed and the shape the dressing will retain.

فصل 10 و 11 کتاب زیستمواد، اندامهای مصنوعی و مهندسی بافت