Polyurethane and Composite Biomaterials Used in Medicine

Composite and polyurethane materials, used in every aspect of our lives, find widespread application in the healthcare sector. Composites and polyurethane belong within the biomaterial group in the biomedical field. Biomaterials, divided into 4 categories, comprise polymers, composites, metals and ceramics. Polymers are biomaterials used as soft tissue replacements. Heart-vessel system and general plastic surgery materials are manufactured from polymers. Polyurethane, a flexible synthetic polymer, is also used in medical devices related to the heart. Following World War II, Polyamide was used in vessel prostheses. In the 1970s, the first synthetic, biodegradable surgical thread was produced from polyglycolic acid. In short, over the last 30 years, more than 40 metals, ceramics and polymers have been used for the repair and renewal of more than 40 different parts of the body [Ahmet Pasinli-Ege University Ege Vocational School]. Polymers used as biomaterials in medical applications include polyethylene (PE), polyurethane (PU), polytetrafluoroethylene (PTFE), polyacetal (PA), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), silicone rubber (SR), polysulfone (PS), polylactic acid (PLA) and polyglycolic acid (PGA).   An important point in biomaterials is that they must possess biocompatibility. Biocompatible; a biomaterial that 'is compatible with the body' is one that does not impede normal changes in surrounding tissues and does not create undesired reactions in tissue (inflammation, clot formation, etc.). Materials with high biocompatibility are used in the preparation of devices that can be implanted in the body. Materials with high biocompatibility—that is, biomaterials—are metals, ceramics, polymers and composite materials. Many polymers such as polyethylene (PE), polyurethane (PU), polytetrafluoroethylene (PTFE), polyacetal (PA), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), silicone rubber (SR), polysulfone (PS), polylactic acid (PLA) and polyglycolic acid (PGA) are used in medical applications. Each material has its own specific application area. Polymers are biomaterials that can be prepared in many different compositions and shapes (fiber, film, gel, bead, nanoparticle). Accordingly, they have a wide range of uses. However, in some applications this situation differs. For example, in the orthopedic field they have quite weak mechanical strength. Nevertheless, they can absorb the structure of liquids and swell or may release unwanted toxic products (monomers, antioxidants, etc.). Biomaterials used in medical applications fall into two groups: biomaterials for hard tissue replacement and biomaterials for soft tissue replacement. While orthopedic and dental implants are generally prepared from metals and ceramics falling within the first group, heart-vessel system and general plastic surgery materials are manufactured from polymers. However, such a classification does not always apply. For example, a heart valve can be made from polymer, metal and carbon; a hip prosthesis can also consist of composites of metals and polymers.

Polymeric Biomaterials

A polymer is defined as a long-chain molecule composed of small, repeating units. The repeated units are called "mers." The small molecular weight units used at the start of synthesis are called "monomers." The properties of polymers differ from their building blocks, monomers. For this reason, selection of an appropriate biomaterial for application areas should be carried out carefully by a biomedical engineer.

Hydrogels

Hydrogels are cross-linked polymeric structures that swell in water. They are prepared through the polymerization reaction of one or more monomers. The most widely used hydrogel in medical applications is cross-linked PHEMA. The common area of application for hydrogels is contact lenses. The main reason for this is their good mechanical stability, high oxygen permeability and suitable refractive index. Other application areas of hydrogels are artificial tendon materials, bio-adhesive substances in wound healing, artificial kidney membranes, artificial skin and aesthetic surgery materials. One of the most important application areas is the pharmaceutical field. It is used in controlled drug-release systems (such as insulin release control). Many glucose-responsive hydrogel systems are prepared from pH-sensitive polymers (HEMA-dimethylaminoethyl methacrylate copolymer). One of the advanced application areas of hydrogels is the development of artificial muscles. Smart hydrogels that convert electrochemical stimuli to mechanical work can function as human muscle tissue. Taking advantage of these properties, artificial muscles can be created.

Natural Polymers:

Polymers produced biologically and possessing inherent functional properties. • Proteins (Collagen, actin, etc.), • Polysaccharides (Starch, cellulose, etc.), • Polynucleotides (DNA and RNA). The production costs of natural polymers are high and they cannot be produced in sufficiently large scales. Natural polymers, having many different applications, are also quite important for the biomaterial field. Since they are similar to or the same as macromolecules in biological environments, when they come into contact with the living body they do not produce undesired reactions such as toxic effects or inflammation. Their disadvantages are difficulty in shaping due to degradation at high temperatures and being immunogenic (causing immune response). Natural polymers are indispensable sources in the biomaterial field. Since they are similar to or the same as macromolecules in biological environments, when they come into contact with the living body they do not produce undesired reactions such as toxic effects or inflammation.

Collagen and Gelatin

In all living organisms, cells form tissues, tissues form systems, and systems form organs and organ systems.

In maintaining this integrity, a structure called connective tissue, which covers a wide area in the organism, plays a role.

The cells that make up connective tissue release most of their metabolism products into the extracellular space after synthesis. These synthesis products include collagen, elastin and proteoglycans.

The term collagen derives from two Greek words; 'kolla' and 'gennan'. 'Kolla' means glue/adhesive, and 'gennan' means making/forming. Collagen is a water-insoluble protein with high tensile strength. In connective tissue and tendons, fibroblasts, and in teeth odontoblasts, are known as specialized cells that synthesize collagen. Collagen, which is a main component of connective tissue in the body, comprises approximately 1/3 of total body proteins. Collagen is found in cartilage at 50%, in the cornea at 68%, and in skin at 74%. Collagen contains 35% glycine and 11% alanine in its structure. For this reason it resembles beta-keratin. Unlike other proteins, collagen contains 12% proline and 9% hydroxyproline.

Polyurethane-Based Wound Dressing Materials

Polyurethanes are widely used as wound dressing materials due to their high biocompatibility, good gas permeability for oxygen and carbon dioxide, excellent mechanical strength and suitable elasticity [Xu et al., 2013, Gharibi et al., 2015]. The polyurethane-based wound dressing materials found in literature are listed below. • Gultekin et al. developed production of polyurethane films with high biocompatibility based on linoleic acid, a main component of triglyceride fats [Gultekin et al., 2008]. • An ideal antibacterial nanofiber wound dressing material was obtained through electrospinning of a solution composed of polyurethane, dextran and ciprofloxacin HCl (CipHCl) drug. • Polyurethane/siloxane-based electroactive, antibacterial and antioxidative wound dressing membranes were prepared by sol-gel condensation, and according to in vitro test results, Gharibi et al. demonstrated that the dressing material prepared caused rapid healing in a wound model [Gharibi et al., 2015]. • Antimicrobial, endotoxin imidazolium-type cationic polyurethane foam wound dressings were prepared by Ding and colleagues [Ding et al., 2019]. Following in vivo results, the antimicrobial potential of the wound dressing material was proven.

Composites

"Composite" can be defined as a multiphase material formed by two or more materials with different chemical structures, while preserving their boundaries and properties. Therefore, a composite material possesses properties that none of its individual constituent components could have alone. A composite material is prepared by incorporating various reinforcing materials into a material called the "matrix." Various polymers are used as the matrix, and mostly glass, carbon or polymer fibers are used as reinforcement, sometimes also mica and various ceramic powders. Composites are envisioned particularly for orthopedic applications because they have high strength and low elastic modulus. Furthermore, by modifying the composition of the composite material, implants can be made to adapt to mechanical and physiological conditions according to their areas of use in the body. Composite materials are more advantageous than homogeneous materials in terms of achieving structural compatibility. Other advantages that polymer composites can provide include corrosion resistance, absence of metal fatigue and metal ion release, and reduced brittleness. Since polymer composites do not carry magnetic properties, they have no adverse effects on magnetic resonance (MRI) and tomography imaging. Metal alloys and ceramics are radio-opaque and cause problems in X-ray radiography. However, radio-opacity in composite materials can be adjusted. Given their light weight and superior mechanical properties, composites are extremely suitable as structural components of such imaging devices.

Chitin and Chitosan

Chitin is a polysaccharide with a long, linear structure. Its structure closely resembles cellulose. Chitin is generally found in the shells of some crustaceans such as crabs, shrimp, and clams, in some marine mollusks such as oyster shells and cuttlebone, and in the shells of some insects such as flies, grasshoppers and spiders. Chitosan is an amorphous polyaminosaccharide obtained through alkaline deacetylation of chitin and is one of the few naturally occurring cationic polyelectrolytes. Chitin is used as raw material in chitosan production. It is commercially produced in Japan and the USA. Chitosan polymer, produced from crab shells under the commercial name Flonac, had 2000 production of 1,250 tonnes/year. The production cost per kilogram ranges between 6 and 32 US dollars depending on product quality and production process.

Medical Application Areas of Composite Materials

Ceramics, while having high biocompatibility and being corrosion-resistant, are hard, brittle materials that are difficult to process, have poor mechanical properties and high density. Composite materials have been developed as alternatives to materials with disadvantages. While orthopedic and dental implants are made from metallic biomaterials and bioceramics, heart-vessel system and general plastic surgery materials are made from polymers. Polymers have weak mechanical strength in the orthopedic field. The tensile strength of polyethylene is around 20-30 MPa. A composite material can be defined as a multiphase material formed by two or more materials with different chemical structures, while preserving their boundaries and properties. Therefore, a composite material possesses properties that none of its constituent components could have alone. A composite material is prepared by incorporating various reinforcing materials into a material called the "matrix." Various polymers are used as the matrix, and mostly glass, carbon or polymer fibers are used as reinforcement, sometimes also mica and various ceramic powders. Composite materials are envisioned particularly for orthopedic applications because they have high strength and low elastic modulus. Furthermore, by modifying the composition of composite materials, implants can be made to adapt to mechanical and physiological conditions according to their areas of use in the body. It is clearly evident that composite materials are more advantageous than homogeneous materials in terms of achieving structural compatibility. Other advantages that composite materials can provide include corrosion resistance, absence of metal fatigue and metal ion release, and reduced brittleness. Metal ions, for example nickel and chromium release, not only weaken the implant but also cause allergic reactions. Composites are used outside orthopedic and dental applications, also as soft tissue implants. Since polymer composites do not carry magnetic properties, they have no adverse effects on magnetic resonance (MRI) and tomography imaging. Prepared by: Nükhet Sezer

Sources 1- Science and Technique Magazine, TÜBİTAK 2- "Selection of Orthopedic Materials According to Their Biocompatibility and Mechanical Properties", Sevki Yılmaz GÜVEN, Süleyman Demirel University, Mechanical Engineering Department, 32260–Isparta 3- "Polyurethane-Based Wound Dressing Materials", Prof. Dr. Süleyman Köytepe, Prof. Dr. Burhan Ateş, Dr. İdil Karaca Açarı, İmren Özcan, İnönü University, Faculty of Arts and Sciences, Chemistry Department 4- "The Importance of Surface in Medical Polymers", Nesrin HASIRCI, Middle East Technical University, Faculty of Arts and Sciences, Chemistry Department,