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Biopolymers – raw materials for innovative medical products

Polyhydroxyalkanoates (PHA) are biodegradable biopolymers that are becoming increasingly important. Bioplastics are now used not only in everyday objects such as plastic bags and yogurt pots but also increasingly in the field of medicine, which is why intensive research into medical devices made from biodegradable polymers such as PHA has been going on for quite some time.

Fluorescence image of bacteria cells (Ralstonia eutropha) that can accumulate large amounts of PHB. The cells were stained with Nile red, the PHB granules appear as red dots inside the cells. © Anja Frank, University of Stuttgart

Every year, over 300 million tons of plastic are produced. The majority is polyester, which is produced from fossil fuels such as oil and gas. However, there is a growing demand for oil-saving, environmentally friendly products made from renewable resources. Nowadays, polyethylene is produced from sugar cane and polylactide from corn. The main benefit of bioplastics is that they save oil.

In addition to sugar cane and corn, polyhydroxyalkanoates (PHA) are also used as raw materials for bioplastics. They are natural storage materials accumulated by bacteria, fungi and some plants when they lack certain nutrients: more than 300 different microorganisms are known to synthesise PHAs. They are carboxylic acid polyesters with one or several OH groups. Three PHA groups can be identified based on the number of carbon atoms they contain: short-, medium- and long-chain PHAs. Thanks to their plastic-like characteristics, polyhydroxyalkanoates are already being used as the basis of many plastics. Polyhydroxybutyrate (PHB) is the most important of the PHA types used for bioplastics production.

Glossary

  • An antibiotic is a bacteriocidal or bacteriostatic substance produced by microorganisms (bacteria, fungi) of which minute concentrations inhibit the growth of bacteria.
  • Bacteria are microscopically small, unicellular organisms belonging to the prokaryotes.
  • Enzymes are catalysts in the living cells. They allow the execution of chemical transformations of the metabolism at body temperature.
  • Escherichia coli (abbr.: E. coli) is a coli bacterium that is common in the human intestines. Variants of this bacterium (E. coli K12), which lack certain characteristics of the wild-type bacterium that are vital to survival in the field, are often used in molecular genetics as the host organism for the cloning of recombinant DNA fragments.
  • Immunology is a scientific discipline dealing amongst others with the defence reactions of humans and animals against organisms such as bacteria, fungi, and viruses, but also with the defence reactions against foreign (non-self) cells and tissue or own (self) cells and tissue (autoimmune reactions).
  • There are two definitions for the term organism: a) Any biological unit which is capable of reproduction and which is autonomous, i.e. that is able to exist without foreign help (microorganisms, fungi, plants, animals including humans). b) Definition from the Gentechnikgesetz (German Genetic Engineering Law): “Any biological unit which is capable of reproducing or transferring genetic material.“ This definition also includes viruses and viroids. In consequence, any genetic engineering work involving these kinds of particles is regulated by the Genetic Engineering Law.
  • A vaccine is a preparation of dead or weakened pathogens (or of derived antigenic determinants) used to induce immunity against the pathogen.
  • Fermentation is the process of converting biological materials with the help of microorganisms or by the addition of enzymes. In its strictest sense, fermentation is the anaerobic oxidation of sugars for the purpose of energy generation of the metabolic organism.
  • A neuron is a nerve cell. A nerve cell consists of a body, an axon and dendrites.
  • Chemotherapy is the treatment of diseases, especially cancer, by means of chemotherapeutic agents (pharmaceuticals that inhibt the growth of (cancer) cells).
  • The toxicity is the poisonousness of a substance.
  • Positron emission tomography (PET) is an imaging technique used to display structures as well as biochemical and physiological processes in the body. This technique is based on the distribution of a radioactive labelled substance in the organism, which then emits positrons and therefore can be detected by a scintillation counter.
  • Plasticity is the attribute of organisms to change their characteristic values under the influence of environmental factors. Therefore, neuroplasticity is the characteristic of neurons to change their response behaviour dependent from their activity. In most cases, the strength of the synaptic transmission is influenced (synaptic plasticity). The neuroplasticity or synaptic plasticity, respectively, is considered to be the basic mechanism in learning processes and in the formation of memories.
  • Polyehylene (abbrevation: PE) is the polymer of ethylene. It belongs to the thermoplastic synthetics.
  • Polyhydroxyalkanoates (PHA) are polyesters made by bacteria, which need them as energy reserve. They can be used industrially as packaging or implant material.
  • Polyhydroxybutyrate (PHB) is the best-known representative of the polyhydroxyalkanoates. PHB is produced biotechnically and is biologically degradable.
  • Pegylation is a chemical modification of a substance by which a Polyethylenglycol (PEG) chain is added in order to change its attributes like its solubility in water.
  • Absorption means in a biological context: the absorption of a drug or of light
  • Biocompatibility means in a literal translation: consistent with the living. It describes the two-way combatibility between a technical and biological system. Materials are biocompatible, when they don't have any negative influence on the organisms in their environment. Biocompatibility is also a measure for the biodegradability of substances in the sewage.
  • Ethylene is a gaseous plant hormone. It is important for germination and senescence processes in plants such as ripeness of fruits, development of flowers, abscission of leaves in autumn and necrosis of plant parts. Ethylene is used in greenhouses to aerate fruits resulting in increasing maturation.
  • Biomolecules which can bind active agents are called targets. They can be receptors, enzymes or ion channels. If agent and target interact with each other the term agent-target-specific effect is used. The identification of targets is very important in biomedical and pharmaceutical research because a specific interaction can help to understand basic biomolecular processes. This is essential to identify new points of application.

Bioplastics in medical application

Important and commonly found polyhydroxyalkanoate: 3-hydroxybutyrate © Wikimedia Commons

Up until now, polyethylene glycol (PEG) and silicone have been the main plastic materials used for medical products. However, they are increasingly being replaced by plastics that are biodegradable and biocompatible. This means that they can be degraded in the body without causing dangerous immune reactions.

The company ITV Denkendorf Product Service GmbH (ITVP) uses materials such as glycolide, lactide, caprolactone and trimethylene carbonate to manufacture medical products. Absorbable, biocompatible plastics such as these are used as surgical suture material, wound dressing foils, membranes for covering burn wounds, and for vascular prostheses. Lactide, which is mainly used for producing absorbable polymers, fulfils a number of requirements. It is biodegradable, biocompatible, and produced from renewable resources such as corn. It therefore not only meets the demands of medical technology, but also saves fossil fuels.

Polyhydroxyalkanoates – biological, biocompatible, biodegradable

Polyhydroxyalkanoates are also biodegradable, just like polylactides. In addition, PHAs are biocompatible, and do not trigger immunological reactions in the human body. Bacterial fermentation is currently the major PHA production method in industry. PHA biopolymers are enzymatically degraded in the human body. PHA biopolymers have already been tested for their suitability as drug matrix or microcapsules. The degradation of the microcapsules enables the sustained release of drugs over a specific period of time. Chemotherapeutics, vaccines and antibiotics can be packaged into minute particles, so-called nanoparticles, and released at a predetermined site in the body. The controlled release of drugs is of key importance for toxic (chemotherapeutics) or sensitive drugs, which must exert their effect only at a particular site in the body, rather than affecting the entire body. The use of PHA-based nanoparticles appears quite promising for use in cancer therapy and the controlled release of drugs at a specific site in the body.

Germany’s largest textile research centre, the Institute for Textile and Process Engineering in Denkendorf (ITV), deals with the regeneration of nerves and, in cooperation with the ITVP, the NMI Natural and Medical Sciences Institute in Reutlingen, and the BG Hospital in Tübingen, has developed a nerve guidance channel that guides regenerating neurons to the muscle and supports their regeneration. Oil-based polymers consisting of trimethylene carbonate and caprolactone were used in this project.

PHAs have also been investigated for their ability to promote nerve regeneration in the spinal cord. Scientists have shown that a scaffold made of PHA promoted cell division, cell adhesion and differentiation. PHAs have also been shown to have an outstanding effect in tissue regeneration. Since these investigations are still at the basic research stage, a great deal of work is still needed before polyhydroxyalkanoates are ready for use in medical technology.

Polyhydroxyalkanoates have a hard time on the market

Biodegradability and biocompatibility gives PHAs advantages over other biopolymers. However, PHAs are difficult to process and production costs are relatively high. Due to the high raw material and process costs and relatively low production volumes, PHAs find it hard to keep up with better known bioplastics such as polylactide. In 2013, only 3.2% of the entire global biopolymer production capacity was used for producing PHAs. Statista1 indicates that in 2011, biopolymers generated a total turnover of a total of 3.44 billion euros, and that 39.4% of these biopolymers were used for producing packaging materials. Revenues of 13.7 billion euros are expected for 2016, which means that the use of bioplastics will increase. The IfBB (Institute for Bioplastics and Biocomposites) expects that Bio-PET will have the largest bioplastics market share. According to Statista, bioplastics will mainly be used for producing plastic bottles.

It is assumed that PHA production will decrease. Successful production of bioplastics from polyhydroxyalkanoates will only be possible when factors such as PHA production rate, yield, quality and size of production facilities are increased. At present, PHA-based plastics are niche products that are only used when biopolymers such as polylactide cannot be used.

Market size share of biopolymer production capacity in 2013. © IfBB – Institute for Bioplastics and Biocomposites 2
Anticipated market size share of biopolymer production capacity in 2018. © IfBB – Institute for Bioplastics and Biocomposites 2
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