Polymers for Medical Applications 1. Polymers for Artificial Joints 2. Bioabsorbable Polymers for surgical applications 3. Adhesives for medical applications

1. Polymers for Artificial Joints Figure (a) Normal joint Figure (b) replacement of the joint is required There are several regenerative treatments, but joint replacement with an artificial joint is the most common and effective treatment

Modern Total Arthoplasty The artificial joint has a sliding interface using a combination of a hard material against a soft material. Hard material: Metallic femoral head Soft material: Polytetrafluoroethylene (PTFE) shell Cement material: cold-curing acrylic cement (polymethylmethacrylate)- to fix the components and to transfer the stress more uniformly

SOFT MATERIALS The soft material made of polytetrafluoroethylene (PTFE), then it was replaced by high density polyethylene (HDPE) and later by ultra high molecular weight polyethylene (UHMWPE). UHMWPE was chosen because of its low friction coefficient, high resistance to wear, high impact resistance, high ductility and stability in the body

Problems of Total Joint Replacement

What are the differences between HDPE and UHMWPE???

The differences between HDPE and UHMWPE Morphology – the chain length of the tie molecules in UHMWPE is much higher than that in HDPE Molecular weight – UHMWPE shows extremely high molecular weight (two to six million), in contrast to 20,000 – 30,000 for regular HDPE, LDPE & LLDPE. Crystallinity & density of UHMWPE are lower than that of HDPE, due to the high molecular weight and chain structure

Chemical Structure

Properties of UHMWPE

Properties of UHMWPE

Processing of UHMWPE Fabrication methods for thermoplastics cannot be applied for processing of UHMWPE When UHMWPE is melted (> crystalline melting temp.), the resin becomes rubbery but does not flow Why the processing of UHMWPE is complicated???

Processing of UHMWPE Require a combination of temperature, high pressure and time. Methods are ram extrusion, compression molding and direct compression molding. The objective of the methods is to apply enough temperature and pressure to fully sinter the UHMWPE particles

Processing of UHMWPE

Wear properties of UHMWPE The abrasion resistance of UHMWPE is The highest of the various materials Relative weight loss vs. type of polymers Relationship between molecular weight of polyethylene and abrasion weight loss Abrasive wear resistance is increased With linearly increasing molecular weight

Wear properties of UHMWPE Problems with UHMWPE in the application of artificial joints- wear particle produced at sliding surfaces- accelerates the loosening Wear particles Formation of particles with diameter < than 1 micron Solution: Use of transfer film Lubrication; a very thin film of Polymer is transferred to the Opposing surface, lead to the Resultant coefficient of friction Being very low Schematic illustration of an artificial hip joint

New processing of UHMWPE To obtain high performance implants-alter the properties of UHMWPE Increased the crystallinity (without causing degradation)- by using temperature greater than 250C and pressure greter than 2,800 atm.- obtained crystallinity over 80% Crosslinking UHMWPE by low-dose γ-ray sterilization in a vacum or inert gas, then stored in oxygen free environment or heat-treated at temp. below the melting point in a vacuun or inert gas Addition of vitamin E- prevent the crack formation

BONE CEMENT Acrylic cement is used for the fixation of total joint prosthesis The cements used in orthopedic surgery are combination of prepolymerized PMMA solid particle and the liquid monomer The powder particles are sphere (30 to 150 µm in diameter), molecular weight of 20,000 to 2 million For the reaction to occur,prepolymerized PMMA needs to contain an initiator, dibenzoyl perioxide (BP)

BONE CEMENT The liquid monomer contains the activator N,N-dimethyl-p-toluidine (DMPT) The monomer will polymerized on its own when exposed to light or heat. To prevent to monomer from polymerizing, the liquid generally contain an inhibitor or retardant, hydroquinone- function to absorb free radical that may occur and initiating the polymerization

Preparation of Bone Cement The prepolymerized + liquid monomer (mixed together), chemical reaction begin with activator (DMPT) and the initiator (BP) combining and releasing a benzoyl peroxide free radical, and react with the monomer. Polymerization begin. Chains with double bond converted to single bond, heat is generated as an exotherm, and the cement cure

Problems of PMMA Bone Cement Strong exothermic setting reaction Toxic effect of the monomer Inability to bond directly to bone - caused loosening at the interface Brittle nature - To overcome these problems, many types of bioactive bone cements have been developed.

To improve the biochemical properties of PMMA bone cement, many types of bioactive particle fillers have been added into the cement Example of particle fillers are glass ceramic, titania (anatase & rutile), etc

Recent studies on Bone Cement + titania particles (K. Goto et al Recent studies on Bone Cement + titania particles (K. Goto et al., Biomaterials 26 (2005)) Figure (c) Shows direct Contact Between bone (B) And Cement (C), while Figure (b) Shows soft Tissue layer Less than 10 um. The soft In (a) and (d) Is thicker Than (b) and (c)

2. Bioabsorbable Polymers for surgical applications Polymeric materials and composites have been used in medical applications; tissue replacement, support of tissues and delivery of drugs Based on their behavior in living tissue, polymeric biomaterials can be divided into; 1)Biostable 2) Bioabsorbable (biodegradable/bioresorbable)

Biostable Polymers Are inert Cause minimal response in surrounding tissue Retain their properties for years Example: polyethylene, polypropylene; used for endoprostheses and sutures

Bioabsorbable (biodegradable/bioresorbable) Temporary internal fixation, can be partially and fully bioabsorbable material Bioabsorbable implant preserve the structure of tissue at the early stage of the healing, example in bone, tendon and tissue After that, the implant decomposes, and stress are gradually transferred to the healing tissue Bioabsorption of the materials induced by the metabolism of the organism

Bioabsorbable (biodegradable/bioresorbable) Bioabsorbable surgical devices need no removal Requirements for bioabsorbable materials; noncarcinogenic, tissue compatible, nontoxic, etc Should not cause morbidity Must provide adequate mechanical strength and stiffness Degradation should occur by hydrolysis in aqueous media

Bioabsorbable Polymers for surgical applications Suture Materials Polyglycolid acid (PGA) and Polylactic acid (PLA) have been used as synthetic bioabsorbable sutures Bioabsorbable sutures are used in the fixation of bone fractures,closure of soft tissue wound, etc

A Typical Suture Line

Polyglycolid Acid (PGA) and Polylactic (PLA) PGA - High molecular weight, hard, tough crystalline polymer, Tm at about 224-226ºC, Tg of 36ºC. PLA – Tm of 174-184ºC, Tg of 57ºC. Such polymers can be processed into fibers, films, rods, screws, plates, clamps, etc Advantages of polymeric materials compared to metal and ceramics; easy and cheap to make

Bioabsorbable Polymers for surgical applications 2) Porous Composites Combining bioabsorbable polymers in porous and nonporous materials Hydroxyapatite powders and blocks have applications in the bone surgery, e.g. to fill the defects Since porous ceramics are brittle, the toughness has been increased by combining them with polymers

Bioabsorbable Polymers for surgical applications 3) Drug Delivery System Polymeric devices for the controlled release of drugs and antibiotic have been studied These polymers show several advantages over traditional repeated dosage methods This technique can save patients from being exposed to greater amounts of drug at the desired site of action

Bioabsorbable Polymers for surgical applications 4) Partially Bioabsorbable Device The reinforcement of bioabsorbable polymeric matrices with biostable fibers produce strong, partially bioabsorbable materials Example; PLA matrix reinforced with carbon fiber, copolymer MMA and N-vinylpyrrolidone reinforced polyamide fibers, etc used for ligaments, tendon, scaffolds, etc.

Example of Bioabsorbable materials in artificial skin Skin damage following severe burns or ulcers, such as diabetic foot ulcers, is notoriously difficult to heal. This is because the dermis cells will not regenerate in the absence of a matrix on which to grow Recently the development of tissue engineering and, in particular, artificial skin has presented advances in this area These artificial skins (keratinocyte seeded IntegraTM, DermagraftTM, and ApligraftTM which contain neonatal cells in combination with matrices formed from bovine collagen or the soluble suture materials polylactic and polyglycolic acids) provide a matrix for dermis growth and the neonatal cells contained in them produce growth factors which promote healing

3. Adhesives for medical applications The use of surgical tissue adhesives in medicine has developed over 40 years Traditionally, the area of tissue reattachment or repair following surgery has been dominated by sutures, staples and wiring Recently, there is a huge potential for tissue adhesives in clinical practice

Pressure Sensitive Adhesives (PSAs) PSAs have been used for adhering wound dressing to skin PSAs have Tg in the range of -20 to -60ºC, which means they are soft materials at room temp. These soft polymers are able to flow and wet out on to a surface and are able to adherence to that surface

Pressure Sensitive Adhesives (PSAs) The bond formed between PSA and substrate is not permenant and can be broken with a measurable force Mid-19th century, the first adhesive plasters were used, the first aid application of dressing become more demanding, and undergone significant development Early adhesive formulations were based on blends of natural rubber and resin. Now PSAs were dominated by acrylic copolymer

Requirement for PSAs Should be permanently and aggressively tacky, adhere with only slight finger pressure Form a strong bond with surfaces Sufficient cohesiveness that it can be removed without leaving a residue Need to be chemically and biologically accepted to the skin-no irritation or sensitization

Requirement for PSAs 5) Adhesives must have sufficient flow to ensure intimate surface contact 6) Must be able to cope with moisture at the skin without compromising performance 7) PSAs should be easily removed with minimal trauma to the skin

Example of First Aid Dressing

Adhesive Types Acrylic Polymer Widely used due to natural adhesive behavior and wide scope of formulation/property tailoring PSAs are typically copolymer composed of ‘hard’ monomer and ‘soft’ monomer The Tg of the resultant polymer can be controlled by the ratio of hard and soft monomers

The nature of alkyl group, R’, can be used to dictate the adhesives properties, by varying the chain length and hydrophilic/hydrophobic nature of the group Chain length

Rubber-Based PSAs Early medical adhesives were based on natural rubber Now changed to synthetic elastomers such as polyisoprene and polyisobutylene Polyisobutylene tend to pack tightly, results in low air and moisture permeability The low Tg of these materials produce flexible material, that are naturally tacky, allowing the polymer to wet out the skin surface

Silicones - Used since mid 1960, have been utilized for tapes, dressing, bandages Typically formulated from silicone resins and polydimethyl siloxane gum To impart cohesive strength, the polymer and resin are crosslink to form a network The properties of the final adhesives can be controlled by ratio of component and the cross-link density

Types of Transdermal Drug Delivery Designs More recently, silicone adhesives were used in transdermal drug delivery system-controlled entry of pharmaceutical into the blood Delivery of an active ingredient through the skin and into the blood vessels before delivery into the target organ