Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for tissue repair and regeneration

Williams, Simon F.; Rizk, Said; Martin, David P.

doi:10.1515/bmt-2013-0009

Cited by 128 publications

(96 citation statements)

References 18 publications

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“…Except for PLLA and PLGA polyhydroxycarboxylic acids, poly(3-hydroxybutyrate) [156] and poly(ε-caprolactone) have been used as well-known biodegradable polymeric materials for manufacturing stents in the research.…”

Section: Polymeric Bioresorbable Stentsmentioning

confidence: 99%

Recent Advances in Manufacturing Innovative Stents

et al. 2020

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Cardiovascular diseases are the most distributed cause of death worldwide. Stenting of arteries as a percutaneous transluminal angioplasty procedure became a promising minimally invasive therapy based on re-opening narrowed arteries by stent insertion. In order to improve and optimize this method, many research groups are focusing on designing new or improving existent stents. Since the beginning of the stent development in 1986, starting with bare-metal stents (BMS), these devices have been continuously enhanced by applying new materials, developing stent coatings based on inorganic and organic compounds including drugs, nanoparticles or biological components such as genes and cells, as well as adapting stent designs with different fabrication technologies. Drug eluting stents (DES) have been developed to overcome the main shortcomings of BMS or coated stents. Coatings are mainly applied to control biocompatibility, degradation rate, protein adsorption, and allow adequate endothelialization in order to ensure better clinical outcome of BMS, reducing restenosis and thrombosis. As coating materials (i) organic polymers: polyurethanes, poly(ε-caprolactone), styrene-b-isobutylene-b-styrene, polyhydroxybutyrates, poly(lactide-co-glycolide), and phosphoryl choline; (ii) biological components: vascular endothelial growth factor (VEGF) and anti-CD34 antibody and (iii) inorganic coatings: noble metals, wide class of oxides, nitrides, silicide and carbide, hydroxyapatite, diamond-like carbon, and others are used. DES were developed to reduce the tissue hyperplasia and in-stent restenosis utilizing antiproliferative substances like paclitaxel, limus (siro-, zotaro-, evero-, bio-, amphi-, tacro-limus), ABT-578, tyrphostin AGL-2043, genes, etc. The innovative solutions aim at overcoming the main limitations of the stent technology, such as in-stent restenosis and stent thrombosis, while maintaining the prime requirements on biocompatibility, biodegradability, and mechanical behavior. This paper provides an overview of the existing stent types, their functionality, materials, and manufacturing conditions demonstrating the still huge potential for the development of promising stent solutions.

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Section: Polymeric Bioresorbable Stentsmentioning

confidence: 99%

Recent Advances in Manufacturing Innovative Stents

et al. 2020

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“…Biodegradation is mediated via agents such as lipases, esterases and PHB depolymerase enzymes [66,67] which hydrolyze PHB into building blocks (hydroxyacids -oligomers, monomers). In vivo the time duration for the biodegradation and resorption of PHA varies with size and processing, but is generally in between 12 and 18 months [18] without producing any toxic products [16,68]. An implant of [P(4HB)] in the body can decompose into 4HB and then excreted from the body in the form of carbon dioxide and water.…”

Section: Biodegradability and Biocompatibilitymentioning

confidence: 99%

“…TephaFLEX® suture fabricated from poly-4-hydroxybutyrate [P(4HB)] has obtained approval from the Food and Drug Administration (FDA) in 2007. [P(4HB)] has shown superior strength characteristics as compared to polypropylene (Prolene®) and polydioxanone (PDSII®) [18]. In recent years, PHA is also found to be employed in biomedical applications especially in tissue engineering [5,19,20], drug delivery [21,22], and in wound management [23,24].…”

mentioning

confidence: 99%

Bioplastic Polyhydroxyalkanoate (PHA): Recent Advances in Modification and Medical Applications

Mukheem¹,

Hossain²,

Shahabuddin³

et al. 2018

Preprint

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A wide variety of bacteria are found to be the tiny factories in the production of polyhydroxyalkanoate (PHA) biopolymer. PHA is the polyesters of 3-hydroxyalkanoic acids which occur in bacteria when the bacteria is subjected to nutrient limitation and simultaneously fed with an excess amount of carbon. This unfavorable condition forces the bacteria to store carbon in the form of resorbable cellular inclusions called PHA. Biosynthesized PHA has the ability to replace the currently feasible harmful petroleum based plastics to biobased plastics. PHA research is being focused mainly on two facts - bulk production of environment friendly low-cost PHA and functional group modification for multiple applications to mankind. Many companies are already producing PHA with highly tunable properties and are looking into economically feasible technologies for mass production of PHA. The core focus of PHA research includes a selection of potential PHA producers and low to zero cost carbon sources such as carbon containing wastages of household, farms and industries. This challenge of “trash to treasure” still remains to attain. Tunable properties of PHA have made them a more interesting biomaterial to blend with suitable biopolymers including bioactive compounds. Under precise physiological environment, PHA blends can deliver promising mechanical properties, acting as effective drug carriers and showing time bound degradation. Perhaps desirably tuned PHA may address many health issues including orthopedics - load bearing cartilage, artificial membranes for kidneys, heart and wound management. PHA has high immunotolerance, low toxicity and sustained biodegradability, which have attracted diverse scientist with many medical advancements such as bioabsorbable sutures and 3D structures. In the near future, it is expected to derive many smart auto controllable products from PHA such as microsphere, which could be utilised for a range of applications much more than just drug delivery. Furthermore, naturally produced hybrid PHA will be an interesting candidate as they possess essential properties for targeted applications without further artificial blending or incorporating any components.

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“…2) could lead to succinate, 1,4-butanediol (69), or glutamate. 4-Hydroxybutyryl-CoA also serves as a precursor for polymerization to polyhydroxyalkanoates (70). Although the equilibrium constant K' ϭ [crotonyl-CoA]/[4-hydroxybutyryl-CoA] ϭ 4.2 (2) favors the synthesis of 4-hydroxybutyrylCoA from crotonyl-CoA, to our knowledge, no natural pathway is yet known which uses 4HBD in this direction.…”

Section: Mutationmentioning

confidence: 99%

Substrate-Induced Radical Formation in 4-Hydroxybutyryl Coenzyme A Dehydratase from Clostridium aminobutyricum

Zhang

Friedrich

Pierik

et al. 2015

Appl Environ Microbiol

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2؉ cluster prior to hydration. We describe an active recombinant 4HBD and variants produced in Escherichia coli. The variants of the cluster ligands (H292C [histidine at position 292 is replaced by cysteine], H292E, C99A, C103A, and C299A) had no measurable dehydratase activity and were composed of monomers, dimers, and tetramers. Variants of other potential catalytic residues were composed only of tetramers and exhibited either no measurable (E257Q, E455Q, and Y296W) hydratase activity or <1% (Y296F and T190V) dehydratase activity. The E455Q variant but not the Y296F or E257Q variant displayed the same spectral changes as the wild-type enzyme after the addition of crotonyl-CoA but at a much lower rate. The results suggest that upon the addition of a substrate, Y296 is deprotonated by E455 and reduces FAD to FADH·, aided by protonation from E257 via T190. In contrast to FADH·, the tyrosyl radical could not be detected by EPR spectroscopy. FADH· appears to initiate the radical dehydration via an allylic ketyl radical that was proposed 19 years ago. The mode of radical generation in 4HBD is without precedent in anaerobic radical chemistry. It differs largely from that in enzymes, which use coenzyme B 12 , S-adenosylmethionine, ATP-driven electron transfer, or flavin-based electron bifurcation for this purpose. 4-Hydroxybutyryl-coenzyme A (CoA) dehydratase (4HBD) catalyzes the reversible dehydration of 4-hydroxybutyryl-CoA to crotonyl-CoA and the irreversible ⌬-isomerization of vinylacetyl-CoA to crotonyl-CoA (Fig. 1). The enzyme was discovered in the fermentation of 4-aminobutyrate (␥-aminobutyrate [GABA]) to ammonia, acetate, and butyrate (Fig. 2) by Clostridium aminobutyricum (1, 2), attributed to cluster XI of the clostridia (3, 4). In this pathway, 4-aminobutyrate is transaminated with 2-oxoglutarate to yield glutamate and succinic semialdehyde (4-oxobutanoate), which is reduced to 4-hydroxybutyrate. Activation to the CoA thioester and dehydration affords crotonyl-CoA, which disproportionates to butyrate and acetate. Energy is conserved via substrate level phosphorylation via acetylphosphate and via electron bifurcation at the electron-transferring flavoprotein (Etf) and butyryl-CoA dehydrogenase (5, 6). The reduced ferredoxin obtained thereby recycles NADH, mediated by NAD-ferredoxin oxidoreductase, also called Rnf, which generates an electrochemical Na ϩ gradient for ATP synthesis (7,8). With one additional dehydrogenase, this pathway is used by Clostridium kluyveri to reduce succinyl-CoA to butyrate (Fig. 2) (9). Autotrophic CO 2 -fixing Crenarchaeota synthesize succinyl-CoA by reductive carboxylations of acetyl-CoA. The pathway depicted in Fig. 2 recycles the carrier molecule acetyl-CoA and forms a second one for biosynthesis (10, 11). The key enzyme of all these conversions is 4HBD, which links lipid and carbohydrate metabolisms. In this work, we study the enzyme in more detail and propose a plausible mechanism of action.4HBD from C. aminobutyricum is a homotetrameric enzyme (4ϫ 56 kDa) containing one 2ϩ...

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Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for tissue repair and regeneration

Cited by 128 publications

References 18 publications

Recent Advances in Manufacturing Innovative Stents

Recent Advances in Manufacturing Innovative Stents

Bioplastic Polyhydroxyalkanoate (PHA): Recent Advances in Modification and Medical Applications

Substrate-Induced Radical Formation in 4-Hydroxybutyryl Coenzyme A Dehydratase from Clostridium aminobutyricum

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