Trends in Molecular Medicine
ReviewPolyhydroxyalkanoates and their advances for biomedical applications
Section snippets
PHAs – bacterially derived polymers
In the pursuit of sustainable biocompatible (see Glossary) and bioresorbable materials for biomedical applications, there has been increasing interest in PHAs [1., 2., 3.]. In contrast to synthetic polymers that are often obtained from fossil fuel sources, PHAs are extracted from bacterial species such as Pseudomonas putida, Cuprivadus necator, Alcaligenes latus, Pseudomonas mendocina, and Bacillus subtilis grown under nutrient-limiting conditions [4] (Figure 1). PHAs degrade under
PHA-based biomedical prototype development
The vast array of biomedical applications based on PHAs can be categorized into four main subgroups: soft tissue, hard tissue, drug delivery, and medical devices (Figure 2). For some of these applications PHAs have been used as coatings for decellularized matrices to prevent immune responses following implantation of an allograft or xenograft of native tissue such as a heart valve [9,10]. A further development in using PHAs as a coating is in the recent pressurized gyration (known as
Soft tissue engineering
Owing to their elastic properties MCL-PHAs {e.g., poly(3-hydroxyoctanoate) [P(3HO]} and poly(3-hydroxyoctanoate-co-3-hydroxydecanoate) [P(3HO-co-3HD]} are preferentially used in soft tissue applications. These include cardiac patches [14], vascular grafts [15], heart valves [16], auricular reconstructions [17], sutures and wound dressings [18], nerve conduits [19., 20., 21.], and cartilage tissue [22., 23., 24., 25.]. The tuneability of PHA mechanical properties via the production of blends or
Hard tissue engineering
Hard tissue applications are focused on bone implants where the emphasis is on SCL-PHAs such as P(3HB) because they provide the mechanical stiffness required. A large variety of PHA blends and composites have been developed to produce viable biodegradable scaffolds with suitable physical and mechanical properties.
Drug delivery
Another application of PHAs is in drug delivery where they have many advantageous properties [56., 57., 58., 59.]. They can be tailored by production methods to release the chosen therapeutic for the specific time-periods required, and can also be modified to reach, and target, chosen areas in the body [60]. Drug delivery systems range from the use of nanoparticles (often injectable) to transdermal materials and devices, oral and pulmonary administration, and drug delivery implants [61]. PHAs
In vivo studies
Many in vivo studies of constructs, such as those shown in Figure 2, have been carried out in different mammalian organisms ranging in size from small rodents such as mice [38,55,71,72] and rats [73] to rabbits [10] and larger mammals such as pigs [9,27,74], sheep [9,16,75,76], and even primates [77]. The implantation of a multitude of PHA constructs into these animal models has shown that PHA devices result in minimal immune responses and have non-toxic degradation products [56].
Rodent in vivo
Clinical trials and regulatory approval of PHA-based devices
Approval has already been gained in the USA and Europe for the clinical use of P(4HB), an SCL-PHA (commercial name TephaFLEX®), in the context of sutures: this product was cleared by the FDA for marketing in the USA in 2007 [56]. Another P(4HB)-based product that is available for clinical use in the USA is PHASIX™ plug and patch, which is used in the repair of inguinal hernias [82]. P(4HB)-based products which have been approved in the USA and Europe are collated in Table 1. It is likely that
Concluding remarks
In the past two decades PHAs are becoming ever more popular owing to their tuneable properties, biocompatibility, and bioresorbability. Furthermore, they are environmentally friendly owing to their sustainable production; however, more research will be necessary to achieve higher yields of PHAs from waste materials to further enhance sustainability [83].
PHAs can be used in a vast array of biomedical fields including soft and hard tissue engineering, drug delivery applications, and medical
Acknowledgments
I.R., D.A.G., and E.A. would like to thank EU Horizon 2020 Bio-Based Industries Joint Undertaking (BBI/JU) project ECOFUNCO (grant agreement 837863) for funding. C.T., A.F., and S.T. were supported by the University of Sheffield.
Declaration of interests
No interests are declared.
Glossary
- Allograft
- transplantation within the same species from one individual to another individual; does not include transplantation between identical twins.
- Aneurysm
- a weakness in a blood vessel leading to a bulge.
- Anterior
- front of the body.
- Autograft
- transplantation within the same individual of tissue from one location to another.
- Avascular
- lack of blood vessels.
- Biocompatible
- not harmful to living tissue.
- Bioresorbable
- naturally absorbed by the body over time.
- Blood–brain barrier
- a highly selective barrier
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