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Polyhydroxyalkanoate review |1

REVIEW
Polyhydroxyalkanoates: Synthesis and Application
Nguyen Nguyen Xuan Vu (BI236), Nguyen Tien Hoang (BI9107)

ABSTRACT
As the humanity is entering the plastic age, the waste from synthetic polymers
has become a major problem since it would take thousands of years for these
material to completely decompose in the environment after being discarded.
A solution that receives many attentions nowadays is developing bio-
degradable polymers that can replace petroleum-based polymers. Such
material includes polyhydroxyalkanoate, a family of polymers synthesized via
bacterial fermentation. The polymers show comparable properties with their
synthetic counterparts, and can be applied in a number of aspects including
food packaging, drug delivery, medical implantation…

1. INTRODUCTION the source but mainly on the nature of the material,


or chemical structure and biodegradation
Biodegradable plastics are plastics that are naturally environment. When a biodegradable material (pure
biodegradable due to the effects of microorganisms polymer, mixed product, or composite) is obtained
such as bacteria, mold, actinomycetes and enzymes, entirely from renewable sources, it is called a green
into CO2, CH4, water, inorganic compounds, polymer material. The life cycle of biodegradable
biomass, without leaving any substances that could polymers is depicted in Figure 1.
harm the environment. The biodegradation of To make sure that plastics are correctly labeled as
plastics depends on the respective external "biodegradable", definitions as listed below should
conditions, which may be anaerobic or aerobic. be carefully:

Aerobic biodegradation: - Bioplastic: a group of materials that meet the


criteria, are either of biomass origin (maize,
Cplastic + O2 → CO2 + H2O + Cfixed + Cbiomass sugarcane, cellulose, etc.) or biodegradable or both;
- Bio-based/ plant-based: A material or product
Anaerobic biodegradation:
(or a part of product) derived from biomass (plant).
Cplastic → CO2 + CH4 + H2O + Cfixed + Cbiomass The source of biomass used in this bioplastic group
is usually corn, sugarcane, cellulose, etc. This group
may or may not be biodegradable.
Biodegradable plastics can be obtained from - Biodegradable: Biodegradation is a chemical
renewable or synthetic sources of petroleum-based process in which microorganisms available in the
chemicals. Mixing of two or more biodegradable environment convert materials into natural
polymers can produce a biodegradable material substances such as CO2, H2O and compost (without
(Biodegradable plastics) that conforms to certain artificial additives). The process of biodegradation
requirements. Biodegradability does not depend on depends on the ambient conditions (light,
Polyhydroxyalkanoate review |2

Figure 1. Life cycle of biodegradable polymers (source: European Bioplastics)

temperature, oxygen, water), depending on the may include heavy metals, or cornstarch, to weaken
nature of the decomposition material. the texture and easily decay.
- Compostable: Can decompose by composting - Hydro-biodegradable plastic: Plastics can be of
under certain conditions, or according to defined biological origin like cornstarch, plants ... or minerals
standards. When a material is compostable, it but biodegradable. These materials are to be
means that it can biodegrade in a given time, under biodegradable, in industrialized areas, under
certain conditions. However, not all 100% of defined conditions, published in the standards for
biodegrable plastic can be composted, because the biodegradable materials.
composting components will lose the usage value of
compost. The production of petroleum based plastics has a big
- Degradable: All plastic materials are capable of disadvantage of generating non-degradable waste
decaying. It is possible to disintegrate plastic by products. The non-biodegradable nature of these
mechanical methods such as, crushing, crushing, products, due to their high molecular mass and
grinding, ... Some plastics are added with additives complex structure imparts a high environmental
to accelerate the decomposition process under burden as they can remain in water bodies, soil and
certain conditions. such as: Light (photodegradable landfill for many years. Concerns over the harmful
plastic) oxygen (Oxo-degradable plastic). effects of these petrochemical derived plastics by
Mechanical decay resins into micro or nano-plastic public and environmental bodies have been
fragments. In the case of chemical decay, the resin increased. This awareness prompted a global
reacts with oxygen in a humid environment, scientific drive to develop alternative green, eco-
promoted by the light into CO2 and water. friendly and biodegradable polyesters and plastics
substitutes such as PHA or PLA
- Oxo-biodegradable plastic: Plastic made from
traditional petroleum-based materials, mixed with Polyhydroxyalkanoates or PHAs are linear
special additives to force it to decay. This additive biopolyesters. They are biodegradable polyesters
produced and stored within cells as energy and
Polyhydroxyalkanoate review |3

carbon storage materials by various test or certificates will definite biodegradable


microorganisms. The French scientist Lemoigne first products, such as:
discovered PHA in Bacillus megaterium in the form
of poly (3-hydroxybutyrate) (PHB) in 1925. Now, - BIP Compostable (Biodegradable Products
researches have shown that PHAs can be produced Institute Compostable): the BPI certified
under both aerobic and anaerobic conditions by compostable program applies science-base testing
more than 90 genera of both Gram-positive and to prove a material that will compost in a municipal
Gram-negative bacteria… PHA have suitable or commercial facility, leaving no toxic or lingering
properties like biocompatibility and plastic residues in the soil. The certified
biodegradability to apply in various industries such compostable program certificate uses a specific set
as biomedical sector including tissue engineering, of testing criteria published by somes standards as
bio-implant patches, drug delivery, surgery and ASTM D6400 for plastic or ASTM D6868 for coated
wound dressing. Accordingly, PHAs are “green paper products or where polymers are used a
plastic” which can replace almost common plastic binder;
made from fossil fuel such as polyethylene (PE), - TUV OK biobased: Product certification based on
polyvinyl chloride (PVC) and polyethylene renewable raw materials. On a basis of the
terephthalate (PET)... determined percentage of renewable raw materials
(% Bio-based), the product can be certified as one-
PHAs’ costs are expensive, due to low yield of star-bio-based, two-star-bio-based, three-star-bio-
fermentation. A PHA plastic bag can be 3 times base or four-star-bio-base. Not all these products
more expensive compared to other material (i.e An are biodegradable;
Phat PHA plastic bag of Vietnam). However, with - TUV OK compost: Packaging or products featuring
positive social and environmental impact when the OK compost INDUSTRIAL label are guaranteed as
compared with conventional plastics in terms of biodegradable in an industrial composting plant.
production and recycling, this material still be This applies to all components, inks and additives.
ameliorating: manufacturers are trying to increase The sole reference point for the certification
the fermentation yields or finding a more programme is the harmonised EN 13432:2000
economical substitute source of Carbon. standard: in any event any product featuring the OK
compost INDUSTRIAL logo complies with the
Plastics can be made absolutely from PHAs. requirement of the EU Packaging Directive
Nevertheless, to reduce the cost, PHAs usually (94/62/EEC);
combine with starch or cellulose. By this way, their - TUV OK compost HOME: Owing to the
biodegradable ability rose. PHAs plastic can degrade comparatively smaller volume of waste involved,
completely in soil where rich microorganism and the temperature in a garden compost heap is clearly
mushroom are in. A special enzyme from the lower and less constant than in an industrial
bacterial damaged PHAs plastic. It takes them about composting environment. This is why composting in
2 months to degrade naturally. However, the the garden is a more difficult, slower-paced process.
process in sea water is much slower than normal, ÜV AUSTRIA’s innovative answer to this challenge
about 50% in 6 months. And there is a drawback of was to develop OK compost HOME to guarantee
this combination method that it can remain non- complete biodegradability in the light of specific
biodegradable waste for example PE in the PE-PHA requirements, even in your garden compost heap.
bottle. OK compost HOME is not based on a standard but is
the basis for several standards, such as: AS 5810 -
Side information Biodegradable plastics suitable for home
composting, NF T 51800 - Specifications for plastics
Nowadays, many plastic products are labeled
suitable for home composting, prEN 17427 -
“biodegradable”, while consumers cannot
Requirements and test scheme for carrier bags
distinguish between biodegradable and non-
biodegradable products. Hence, some standards
Polyhydroxyalkanoate review |4

suitable for treatment in well-managed home there are not any standards but they are applied via
composting installations; GreenPla program (responded about 60% of organic
- TUV OK biodegradable SOIL: Biodegradability in materials transform to CO2 in minimum). Here some
the soil offers huge benefits for agricultural and trademarks are popular such as ABA Compostable
horticultural products, as they can be left to break Seedling, TUV OK Compost, the DIN-Geprüft
down in situ after being used. The OK biodegradable Industrial Compostable Mark and BPI Compostable.
SOIL label is a guarantee a product will completely
biodegrade in the soil without adversely affecting According to the survey of patent registration based
the environment; on Thomson Innovation database, it shows:
- TUV OK biodegradable WATER: Products certified
for OK biodegradable WATER guarantee - About 1446 patents related to biodegradable
biodegradation in a natural fresh water plastic have been registered for protection (from
environment, and thus substantially contribute to 1977-2015). The first patent, in 1977, filed in France
the reduction of waste in rivers, lakes or any natural involved the design of making a box made from
fresh water. Note that this not automatically biodegradable plastic;
guarantees biodegradation in marine waters;
- From 1977-1989, the number of patents applied
- Din-Certo v: Din-Certo certify industrial
for registration was not much (<10 inventions/year),
compostable products accroding to EN 13432 and
soared in 1990 with nearly 30 patents and peaked in
other national and international standards, where
2002 with 92 patents;
applicable. DIN CERTCO Gesellschaft für
Konformitätsbewertung mbH offers certification for - Currently, patents related to biodegradable
products made from biodegradable materials which plastic are being applied for protection in about 42
are compatible with home and garden composting. countries around the world, mainly in Japan, China,
It awards the "DIN-Geprüft home compostable" USA, Korea and Germany.
mark for this, along with an individual registration
number. Compostability linked with In addition, there are currently about 180
biodegradability represents an important element enterprises specializing in manufacturing bioplastics
of the recycle management system. The in general and biodegradable plastics in particular.
internationally recognised "DIN-Geprüft" mark from Among them, there are 45 companies in Germany,
DIN CERTCO can now also be awarded to products USA and Japan. According to estimation, by 2020,
which can be composted in the garden. Certification the market share of the bioplastic industry has a
is possible on the basis of the following current turnover of about US $ 30 billion, by 2030 expected
standard: AS 5810, NF T 518000. to reach US $ 324 billion.

Products that stand on ASTM D6400 or D6868 This information shows that the development of
standard are considered biodegradable abilities. biodegradable plastic production technology has
However, in the marine environment, ASTM D6691 great potential and is the general development
is applied. In compost home case, some standards trend of the plastic industry worldwide.
are used such as: AS 5810 and AS 4736 in Australia,
NF T 51800 in France, EN 17427 in Europe,
certificates from TUV Din-Certo in Austria-Belgium
as: OK Compost Home, DIN-OK Compost Home, DIN-
Geprüft Home Compostable Mark and Australasian
Bioplastics Association (ABA) Home Compostable.

Others will be applied for products that compost in


an anaerobic environment industry like
EN/13432/14995, EN 13432 - packing, EN 14995 –
plastic in Europe, ASTM D6400 in the USA. In Japan,
Polyhydroxyalkanoate review |5

1. MOLECULAR STRUCTURE OF PHA PHA granules are accumulated inside the bacteria in
the presence of an excess carbon source and a
PHAs are polyhydroxyesters of 3, 4, 5 and 6-
deprivation of other elements, such as nitrogen [2].
hydroxylalkanoic acids. The monomers are either
There are three factors could affect the products:
achiral or chiral with R configuration (Figure 2) [1].
the microorganism used, the carbon source and the
fermentation condition.
PHA synthases are the crucial enzymes of the
biosynthesis of PHA. Therefore, only bacteria strains
that contain this type of enzyme could be used to
produce PHA, such as Alcaligenes, Pseudomonas,
Enterobacter, Necator, Rhodobacter, Ralstonia and
Cupriavidus. Under suitable condition, certain
cyanobacteria and halophiles can also accumulate
PHAs [3].
It is also stated that, not only the biocatalysts are
responsible for the structure, composition and
Figure 2. General structure of PHAs and
properties of PHAs but also the carbon substrate
some examples.
used to growth them. Since the substrate molecules
The PHA polymers are sorted into 2 types: short- need to be transported through the rigid thick cell
chain-length PHA (scl-PHA) and medium-chain- wall of the microorganism, it is preferred for the
length PHA (mcl-PHA). 3-hydroxylbutyrate (3HB), 3- molecules to be small. Large polymeric molecules
hydroxylvalerate (3HV) and 4-hydroxylbutyrate need to be pretreated extracellularly either by a
(4HB) are the most common building blocks chemical process or by the microorganism itself to
representing for scl-PHA. The mcl-PHAs are made up become smaller for utilization. Generally, the
of building block of at least 6 carbon atoms. substrates can be categorized into three types:
Examples of the monomers are 3- simple sugars, triacylglycerol and hydrocarbons.
hydroxylhexanoate (HHx) and 3-hydroxyloctanoate Simple sugars can be used by most of the PHA-
(HO). In addition to these simple representatives, producing bacteria, and triacylglycerol is usable for
the side chains of mcl-PHAs can contain chemical a limited range of microorganism. Only
functionalities such as double bonds, aromatic rings, Pseudomonas species can undergo hydrocarbon
functional groups or chemical elements like metabolism. Using a same substrate, different
halogens, nitrogen, sulfur…[1] microorganism can produce different PHAs
composition. The information about substrates and
2. BIOSYNTHESIS AND PRODUCTION
their corresponding bacteria and products is
Briefly, PHAs are synthesized from various bacterial summarized in Figure 3 [4].
strains and renewable organic carbon sources.
Most of the carbon sources used in recent industrial
Under limited-nutrient condition, the bacteria can
manufacturing of PHAs are food-based, namely food
stack carbon inside their cells as energy reservoir or
crops, sugar cane and vegetable oils, as listed in
fat under the form of PHAs. The PHAs are then
Table 1. This results in a competition between the
purified and collected for further processing. By
production of carbon source and food supply
changing the bacteria family and carbon source,
production. For example, 34,000 tons of PHA
different PHAs can be produced.
produced per year would utilize about 126,000 tons
2.1. Biosynthesis of corn [4]. Thus a matter of interest now is to find
Polyhydroxyalkanoate review |6

Figure 3. A summary of the substrate and microorganism that can biosynthesis PHAs. Blue arrows
indicate substrates added later during the fermentation process to make copolymers.

Table 1. Various PHA producers and their carbon source used

a non-food-based carbon source, or better, recycle production wastes; and lipids from plant and animal
the wasted carbon. These carbon source could be waste (M. Koller, 2014).
molasses; lactose from whey; cellulose hydrolysates
Another crucial factor is the fermentation process.
from the reject fiber wastes from the paper
At first the bacteria strain is cultivated in mineral
industry; glycerol and methanol from biodiesel
medium which contains all necessary elements for
Polyhydroxyalkanoate review |7

the growth of the bacteria, namely phosphor (from be considered are: pH, temperature, shaking rate,
phosphate salts), nitrogen (from urea) and some fermentation scheme. These factors, in combination
metal ions, along with an excess amount of carbon with microorganism strains and carbon sources
from a carbon source like sugar or fatty acid. After would determine the composition of PHAs as
other elements are depleted, the microorganism illustrated by examples listed in Table 2 [3].
starts to accumulate the carbon intracellularly
under the form of PHAs [5]. Parameters that need to

Table 2. PHA synthesized under various condition


Polyhydroxyalkanoate review |8

The metabolism process of the microorganism


follows several pathways as shown in Figure 4. The
sugars follow glycosylation pathway, which is
contributed by the enzymes β-ketothiolase (phaA),
acetoacetyl-coenzyme A (CoA) reductase (phaB),
PHA synthase (phaC). Take glucose for example,
after enter the cell, the sugar is glycolysized to
become acetyl –CoA. Two acetyl-CoA molecules are
condensed to form acetoacetyl-CoA, catalyzed by β-
ketothiolase. The compound is subsequently
reduced to 3-hydroxylbutyryl CoA, which is the
monomer for P3HB, by the reductase. Finally, the
PHA synthase catalyses the condensation of the
monomers to form P3HB. An alternative pathway is
the β–oxidation pathway, in which the anoyl-
coenzyme A hydratase (PhaJ) and 3-ketoacyl acyl
carrier protein (ACP) reductase (FabG) are
responsible for converting the 3-enoyl-CoA and 3-
ketoacyl-CoA, respectively, to (R)-3-hydroxyacyl-
CoA. The β–oxidation pathway is more preferred by Figure 5. General overview of PHA production
fatty acids, therefore the main products of this process
pathway are mcl-PHAs [5].
fermentation step, but generally they can be
categorized into discontinuous and continuous
configurations. Typically, P(3HB-co-3HV), which is
sold under the trade name BIOPOL, has been
produced in 200,000l fermenters. The fermentation
utilizes 2 steps fed batch process, using a mutant of
Ralstonia eutropha as the microorganism. During
the first step, the bacteria are growth in a mineral
salt medium containing a calculated amount of
phosphate and glucose as the sole carbon source. As
the cells grow, phosphate is depleted from the
Figure 4. Intracellular pathways of PHA biosynthesis. medium. In the second step, as the phosphate runs
Abbreviation: PhaA, β-ketothiolase; PhaB, out, the polymers start to be produced and stored
acetoacetyl-coenzyme A (CoA) reductase; PhaC, PHA inside the bacteria cells, with glucose fed to the
synthase; FabG, 3-ketoacyl acyl carrier protein (ACP)
culture. It takes 48h for each step. This procedure
reductase; PhaJ, anoyl-coe.
can produce BIOPOL at a yield of 100g/l [6].
After the fermentation process, the PHA need to be
In industrial PHA production, all processes consist of separated from the cells via recovery step, using
a fermentation step, followed by recovery step and conventional procedure such as centrifugation,
further processing for specific application (Figure 5) filtration, or flocculation-centrifugation. The
[6]. There can be several schemes for the common method involves the extraction of polymer
Polyhydroxyalkanoate review |9

using solvents (chloroform, methylene chloride, Table 3. Characteristic thermos-mechanic features


propylene carbonate, dichloroethane) to dissolve of poly (3HB-co-3HV) at different ratio of 3HV
the PHAs. However, this method requires a large monomer
amount of solvent. Alternatively, a non-solvent
recovery process has been developed. After expose
to a temperature of 80oC, the broth is treated with
a mixture of hydrolytic enzyme of lysozyme,
phospholipase, lecithinase, the proteinase alcalse,
and others. These enzymes can hydrolyze the
cellular components, leaving the polymer remains
intact. After washing, flocculation and drying, the
polymer is collected [6].
3. PROPERTIES
3.1. Physical properties
The simplest case of homopolymer poly(3-(R)- For the case of mcl-PHAs, such as 3-
hydroxylbutyrate) (PHB) is a highly crystalline and hydroxylhexanoate (HHx) or 3-hydroxyoctanoate
brittle thermoplastic. It has the melting point of (HO), they are softer, lower crystallinity and lower
175oC, which is slightly lower than its degrading melting point. They also have extremely low glass
temperature (185oC), makes it difficult for molding transition temperature, make them suitable for
processing. However, PHB exhibits good moisture storing foods under freezing condition.
resistance, water insolubility and optical purity. 3.2. Biodegradability
To be able to use PHB for cases that requires PHAs are classified as biodegradable polymers. They
flexibility, one must decrease its brittleness, as well are considered as energy source for the
as separate the melting point from degrading point. microorganisms. Under microbially active
This can be achieved by blending PHB with other environments, PHAs are degraded into smaller units
polymers or producing copolymer of 3- or monomers, which are used by the cells as carbon
hydroxylbutyrate with another monomer, such as 3- source for biomass growth. The end products of the
hydroxylvalerate (3HV). Take the case of poly (3HB- biodegradation process are carbon dioxide and
co-3HV) as example, by changing the composition of water in aerobic condition and methane in
the two monomers, one can tune the properties of anaerobic condition. The degradation rate depends
this copolymers. It is reported that the elongation at on many factors, including surface area, pH,
break of the material increases and the melting temperature, moisture, concentration of other
point decreases as the 3HV fraction increase, nutrient materials and the activity of the
without any change in the degrading point (Table 3) microorganism. For example, it has been reported
[7]. This allows melt extrusion, injection molding or that poly(HB-co-HV) is degraded completely after 6,
thermoforming without thermal degradation. 75 and 350 weeks in anaerobic sewage, soil and sea
Others scl-PHAs more or less share the same traits, water, respectively [8].
like poly(4-hydroxylbutyrate) represents a highly
elastic material with an enormous elongation to 4. APPLICATIONS
break up to 1000% and a glass transition The properties of PHAs has drawn interest as
temperature as low as -50oC. biocompatible plastics for a wide range of
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applications, namely packaging, medical implant, 4.2. Medical applications


drug carrier… 4.2.1. Tissue engineering
4.1. Food packaging It has been verified by several reports, including in
vivo and in vitro studies, that PHA family is highly
The properties of PHAs meet many required
biocompatible with blood, bone, cartilage tissue and
features to be applied as food packaging. The
other cell lines [12]–[14]. Moreover, PHA polymers
materials must be able to flexible enough to be able
cover a wide range of materials, from soft and
to enclose the food, but also protect it from the
elastomeric to hard and brittle materials, make
environment like microbial attack, UV- radiation,
them flexible to be applied in numerous biomedical
chemical and mechanical damage.
applications. For the past few decades, PHB,
Bucci et al. has conducted several experiments to copolymers of 3-hydroxylbutyrate and poly 4-
test the mechanical properties of PHB jars, whether hydroxybutyrate (P4HB), PHBV, copolymers of 3-
it is suitable for food packaging compared with poly hydroxybutyrate and 3-hydroxyhexanoate
propylene (PP). It is shown that compared to PP, (PHBHHx) and poly 3-hydroxyoctanoate (PHO) and
PHB exhibits a significantly lower resistance to their composite have been used to develop several
dynamic compression. The deformation value of conventional medical devices and tissue
PHB is only around 50% of PP. Under normal engineering. Commercial products of PHA in
refrigerator condition, the performance of PHB is biomedical applications include a variety of forms,
worse than PP in term of mechanical stability. such as suture, pins, screw, films, nonwoven fibrous
However, at high temperature condition, PHB materials…
shown higher strength. Also, the sensorial test
During the process of producing PHA, there can be a
shown that PHB can substitute PP in packaging for
pyrogen such as an endotoxin, which can be a
the storage of fat rich foods, both in freezers and
problem for implanting purpose, contained inside
microwave ovens [9]. In another work of the same
the material. Therefore, the pyrogen needs to be
author, it is revealed that PHB can act as UV light
removed by an oxidizing agent such as hydrogen
barrier. The transmission was zero in the region of
peroxide and benzoyl peroxide to reduce the
250-350 nm [10].
pyrogen content so that the PHA does not elicit an
Another property needs to be considered is acute inflammatory response when implanted in a
chemical (oxygen, water, CO2) permeability. This body.
property will determine whether the material is
It has been reported by Doyle et al. that PHB-based
suitable to be a chemical barrier for long
materials have been implanted to support bone
conservation of foods.
tissue regeneration. It is observed that a consistent
The water vapor permeability Is quantified by the new bone tissue growth produced by the materials
water vapor permeability coefficient (WVPC) or the around the implants without any inflammatory
water vapor transfer rate (WVTR). Several polymers response after 12 months of implantation.
films of the same thickness were prepared and the However, PHA pure polymers still have less
WVTR values are measured at a same condition. The bioactivity function than the native host tissues, and
results show that PHBV has significantly lower they are often to mechanically weak to meet the
WVTR value compared with other related polymers adequate performance. This problem can be solved
[11]. It is also noted that, as the molar ratio of 3HV by adding inorganic bioceramic materials, such as
in PHBV increases, the gas permeability of the hydroxylapatite (HA), zirconia and alumina,
material also increases [11]. bioactive glasses and resorbable calcium
P o l y h y d r o x y a l k a n o a t e r e v i e w | 11

phosphate-based bioceramics. The addition of the


bioceramic materials can enhance both mechanical
property and biological activity of PHA [15].
PHA is also a promising material for developing
tissue-engineered blood vessels. The candidate
materials are P3HB, P4HB, PBHHx and PHO [16].
4.2.2. Drug delivery
The applications of PHAs in drug delivery are based
on their biodegradability and hydrophobic behavior,
makes them be able encapsulate hydrophobic drugs
efficiently in the form of micro- and nanoparticles. A Figure 7. General routes for fabrication of PHA-based
large effort has been put to investigate PHAs such as medical devices.
PHB and PHBV for the fabrication of microcapsules
and microspheres for a large number of drugs,
including anesthetics, antibiotics, anti-inflammatory
agents, anticancer agents, hormones, steroids, and
vaccines [17]–[21].
PHB and P(HB-co-HV) have been researched as
matrix carriers for the drug delivery of antibiotics
and drug molecules. The releasing period of the
materials ranges from 15 to 60 days. The period is
affected by the molecular mass of the polymers
being used. As the molecular mass increases, the
Figure 8. PHA market growth analysis. Abbreviation:
release rate is generally slowed down. For the case
APAC = Asia-Pacific Region; ROW = Rest of World
of P(HB-co-HV), the releasing time length also
depends on the percentage of HV component in the In 2019, the market size of PHA reached USD 57
copolymers, that is, as the percentage of HV million, which is still relatively small compared with
increases, the release rate is increased and vice PE market (~USD 174 billion in 2018). The market
versa [22]–[26]. shows a gradual increment over the last 3 years and
is predicted to keep increasing and reach USD 98
Figure 7 summarizes the process routes for the
million in 2024 (Figure 8).
fabrication of PHA-based materials.
In Vietnam, the producing of PHA has been initiated
5. PHA MARKET
by An Phat Group for food-based applications.
One challenge for PHA for its wide application is its
6. CONCLUSIONS
high production cost. The price of PHA is estimated
to range from US$ 2.25 to US$ 2.75/lb, which is 3-4 Although synthetic polymers exhibit excellent
times higher than the price of conventional mechanical features and play an important part in
polymers like PP and PE [27]. Therefore, currently our daily life, the waste of these materials have
PHAs are only considered to be applied in advanced become a threat for the environment. PHAs are a
applications. family of polymers that can biodegrade by the
microorganisms to become environmentally
P o l y h y d r o x y a l k a n o a t e r e v i e w | 12

harmless substances like CO2 and water. The PHAs [6] G. D. Christian et al., “Production of
are biosynthesized using a group of bacteria Microbial Polyesters :,” Managing, vol. 71,
containing PHA synthases. The polymers are no. 4, p. 10, 2001.
accumulated intracellularly as a carbon stock of the [7] K. Khosravi-Darani and D. Z. Bucci,
cells as others nutrient components are depleted. “Application of poly(hydroxyalkanoate) in
The PHAs having many commons in term of food packaging: Improvements by
physicochemical and thermomechanical properties nanotechnology,” Chem. Biochem. Eng. Q.,
with their petroleum-based counterparts like PP vol. 29, no. 2, pp. 275–285, 2015.
and PE. By changing the production condition, these
[8] “Production of Polyhydroxyalkanoates , a
properties can be controlled. bacterial biodegradable polymer,” vol. 3, no.
Since the PHAs family covers a wide range of January, pp. 18–24, 2004.
materials, it can be implemented in a variety of [9] D. Z. Bucci, L. B. B. Tavares, and I. Sell, “PHB
aspects, from food containers to biological devices. packaging for the storage of food products,”
However, the high cost of production remains as a vol. 24, pp. 564–571, 2005.
barrier for wide application of PHA.
[10] D. Z. Ã. Bucci, L. B. B. Tavares, and I. Sell,
 REFERENCES “ARTICLE IN PRESS POLYMER Biodegradation
and physical evaluation of PHB packaging,”
[1] N. Graz, “Poly ( hydroxyalkanoates ) for Food vol. 26, pp. 908–915, 2007.
Packaging : Application and Attempts
towards Implementation,” vol. 1, no. 1, pp. [11] R. Shogren, “Water vapor permeability of
3–15, 2014. biodegradable polymers,” J. Environ. Polym.
Degrad., vol. 5, no. 2, pp. 91–95, 1997.
[2] M. S. M. Annuar, I. K. P. Tan, and K. B.
Ramachandran, “Research Note: Evaluation [12] Anon, “Free-market energy prices close G-
of nitrogen sources for growth and P’s Bellingham, Wash., mill,” Pulp Pap.
production of medium-chain-length poly-(3- Week, vol. 22, no. 47, pp. 5–21, 2000.
hydroxyalkanoates) from palm kernel oil by [13] J. Zhang, E. I. Shishatskaya, T. G. Volova, L. F.
Pseudomonas putida PGA1,” Asia-Pacific J. da Silva, and G. Q. Chen,
Mol. Biol. Biotechnol., vol. 16, no. 1, pp. 11– “Polyhydroxyalkanoates (PHA) for
15, 2008. therapeutic applications,” Mater. Sci. Eng. C,
[3] A. M. Gumel, M. S. M. Annuar, and Y. Chisti, vol. 86, pp. 144–150, 2018.
“Recent Advances in the Production, [14] Brigham and Sinskey, “Applications of
Recovery and Applications of Polyhydroxyalkanoates in the Medical
Polyhydroxyalkanoates,” J. Polym. Environ., Industry,” Int. J. Biotechnol. Wellness Ind.,
vol. 21, no. 2, pp. 580–605, 2013. pp. 53–60, 2012.
[4] G. Jiang et al., “Carbon Sources for [15] C. Doyle, E. T. Tanner, and W. Bonfield, “In
Polyhydroxyalkanoates and an Integrated vitro and in tivo evaluation of
Biorefinery,” 2016. polyhydrogbutyrate and of
[5] K. Numata et al., “Synthesis of poly- and polyhydroxybutyuQrate reinforced with
oligo(hydroxyalkanoate)s by deep-sea hydroqyapatite,” pp. 841–847, 1990.
bacteria, Colwellia spp., Moritella spp., and [16] M. Generali, P. E. Dijkman, and S. P.
Shewanella spp,” Polym. J., vol. 45, no. 10, Hoerstrup, “BIORESORBABLE SCAFFOLDS
pp. 1094–1100, 2013. FOR CARDIOVASCULAR TISSUE
P o l y h y d r o x y a l k a n o a t e r e v i e w | 13

ENGINEERING,” no. July, pp. 91–99, 2014. polyhydroxyalkanoate granule binding


protein PhaP fused with targeted cell
[17] “Tramadol encapsulated into
ligands,” Biomaterials, vol. 29, no. 36, pp.
polyhydroxybutyrate microspheres:,” pp.
4823–4830, 2008.
1006–1012, 2003.
[23] M. F. Yagmurlu, F. Korkusuz, I. Gu, P.
[18] G. A. R. Nobes and R. H. Marchessault,
Korkusuz, Ü. Örs, and V. Hasirci,
“Polyhydroxyal kanoates : Materials for
“hydroxyvalerate ( PHBV ) local antibiotic
Delivery Systems,” pp. 167–177, 1998.
delivery system : In vivo effectiveness and
[19] A. V Murueva, E. I. Shishatskaya, A. M. biocompatibility in the treatment of implant-
Kuzmina, T. G. Volova, and A. J. Sinskey, related experimental osteomyelitis,” 1999.
“Microparticles prepared from
[24] S. Rossi, A. O. Azghani, and A. Omri, “release
biodegradable polyhydroxyalkanoates as
system,” vol. 54, no. 6, pp. 1013–1018, 2004.
matrix for encapsulation of cytostatic drug,”
pp. 1905–1915, 2013. [25] H. Li and J. Chang, “Preparation ,
characterization and in vitro release of
[20] A. A. Amirul, E. Wahid, and K. Bhubalan,
gentamicin from PHBV / wollastonite
“Characterization and cytotoxicity of
composite microspheres,” vol. 107, pp. 463–
Polyhydroxyalkanoate microparticles as
473, 2005.
adjuvant matrix for the immobilization of
Pasteurella multocida whole-cell vaccine [26] A. C. Kassab, K. Xu, E. B. Denkbas, and Y.
MATRIX FOR THE IMMOBILIZATION OF Dou, “Journal of Biomaterials Science ,
Pasteurella multocida,” no. October 2018, Rifampicin carrying polyhydroxybutyrate
2017. microspheres as a potential
chemoembolization agent,” no. March 2015,
[21] N. U. T. A. N. Gangrade and J. C. Price,
pp. 37–41, 2012.
“Poly(hydr0xybutyrate-hydroxyvalerate)
microspheres containing progesterone: [27] E. Elmowafy, A. Abdal-Hay, A. Skouras, M.
preparation, morphology and release Tiboni, L. Casettari, and V. Guarino,
properties,” vol. 8, no. 2, pp. 185–202, 1991. “Polyhydroxyalkanoate (PHA): Applications
in drug delivery and tissue engineering,”
[22] Y. Yao et al., “Biomaterials A specific drug
Expert Rev. Med. Devices, vol. 16, no. 6, pp.
targeting system based on
467–482, 2019.

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