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Chaber P, Andrä-Żmuda S, Śmigiel-Gac N, Zięba M, Dawid K, Martinka Maksymiak M, Adamus G. Enhancing the Potential of PHAs in Tissue Engineering Applications: A Review of Chemical Modification Methods. MATERIALS (BASEL, SWITZERLAND) 2024; 17:5829. [PMID: 39685265 DOI: 10.3390/ma17235829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 11/22/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024]
Abstract
Polyhydroxyalkanoates (PHAs) are a family of polyesters produced by many microbial species. These naturally occurring polymers are widely used in tissue engineering because of their in vivo degradability and excellent biocompatibility. The best studied among them is poly(3-hydroxybutyrate) (PHB) and its copolymer with 3-hydroxyvaleric acid (PHBV). Despite their superior properties, PHB and PHBV suffer from high crystallinity, poor mechanical properties, a slow resorption rate, and inherent hydrophobicity. Not only are PHB and PHBV hydrophobic, but almost all members of the PHA family struggle because of this characteristic. One can overcome the limitations of microbial polyesters by modifying their bulk or surface chemical composition. Therefore, researchers have put much effort into developing methods for the chemical modification of PHAs. This paper explores a rarely addressed topic in review articles-chemical methods for modifying the structure of PHB and PHBV to enhance their suitability as biomaterials for tissue engineering applications. Different chemical strategies for improving the wettability and mechanical properties of PHA scaffolds are discussed in this review. The properties of PHAs that are important for their applications in tissue engineering are also discussed.
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Affiliation(s)
- Paweł Chaber
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowska 34, 41-819 Zabrze, Poland
| | - Silke Andrä-Żmuda
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowska 34, 41-819 Zabrze, Poland
| | - Natalia Śmigiel-Gac
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowska 34, 41-819 Zabrze, Poland
| | - Magdalena Zięba
- Department of Optoelectronics, Silesian University of Technology, ul. B. Krzywoustego 2, 44-100 Gliwice, Poland
| | - Kamil Dawid
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowska 34, 41-819 Zabrze, Poland
| | - Magdalena Martinka Maksymiak
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowska 34, 41-819 Zabrze, Poland
| | - Grażyna Adamus
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowska 34, 41-819 Zabrze, Poland
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Ladhari S, Vu NN, Boisvert C, Saidi A, Nguyen-Tri P. Recent Development of Polyhydroxyalkanoates (PHA)-Based Materials for Antibacterial Applications: A Review. ACS APPLIED BIO MATERIALS 2023; 6:1398-1430. [PMID: 36912908 DOI: 10.1021/acsabm.3c00078] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2023]
Abstract
The diseases caused by microorganisms are innumerable existing on this planet. Nevertheless, increasing antimicrobial resistance has become an urgent global challenge. Thus, in recent decades, bactericidal materials have been considered promising candidates to combat bacterial pathogens. Recently, polyhydroxyalkanoates (PHAs) have been used as green and biodegradable materials in various promising alternative applications, especially in healthcare for antiviral or antiviral purposes. However, it lacks a systematic review of the recent application of this emerging material for antibacterial applications. Therefore, the ultimate goal of this review is to provide a critical review of the state of the art recent development of PHA biopolymers in terms of cutting-edge production technologies as well as promising application fields. In addition, special attention was given to collecting scientific information on antibacterial agents that can potentially be incorporated into PHA materials for biological and durable antimicrobial protection. Furthermore, the current research gaps are declared, and future research perspectives are proposed to better understand the properties of these biopolymers as well as their possible applications.
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Affiliation(s)
- Safa Ladhari
- Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada.,Laboratory of Advanced Materials for Energy and Environment, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada
| | - Nhu-Nang Vu
- Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada.,Laboratory of Advanced Materials for Energy and Environment, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada
| | - Cédrik Boisvert
- Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada.,Laboratory of Advanced Materials for Energy and Environment, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada
| | - Alireza Saidi
- Laboratory of Advanced Materials for Energy and Environment, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada.,Institut de Recherche Robert-Sauvé en Santé et Sécurité du Travail (IRSST), 505 Boulevard de Maisonneuve Ouest, Montréal, Québec H3A 3C2, Canada
| | - Phuong Nguyen-Tri
- Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada.,Laboratory of Advanced Materials for Energy and Environment, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada
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Afshar A, Gultekinoglu M, Edirisinghe M. Binary polymer systems for biomedical applications. INTERNATIONAL MATERIALS REVIEWS 2023; 68:184-224. [DOI: 10.1080/09506608.2022.2069451] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 04/08/2022] [Indexed: 01/06/2025]
Affiliation(s)
- Ayda Afshar
- Department of Mechanical Engineering, University College London, London, UK
| | - Merve Gultekinoglu
- Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
| | - Mohan Edirisinghe
- Department of Mechanical Engineering, University College London, London, UK
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Tang HJ, Neoh SZ, Sudesh K. A review on poly(3-hydroxybutyrate- co-3-hydroxyhexanoate) [P(3HB- co-3HHx)] and genetic modifications that affect its production. Front Bioeng Biotechnol 2022; 10:1057067. [PMID: 36545679 PMCID: PMC9760699 DOI: 10.3389/fbioe.2022.1057067] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 11/16/2022] [Indexed: 12/09/2022] Open
Abstract
Polyhydroxyalkanoates (PHAs) have garnered global attention to replace petroleum-based plastics in certain applications due to their biodegradability and sustainability. Among the different types of PHAs, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HHx)] copolymer has similar properties to commodity plastics, making them a suitable candidate to replace certain types of single-use plastics, medical devices, and packaging materials. The degradation rate of P(3HB-co-3HHx) is faster than the commercial petroleum-based plastics which take a very long time to be degraded, causing harmful pollution to both land and marine ecosystem. The biodegradability of the P(3HB-co-3HHx) is also dependent on its 3HHx molar composition which in turn influences the crystallinity of the material. Various metabolic pathways like the common PHA biosynthesis pathway, which involves phaA, phaB, and phaC, β-oxidation, and fatty acids de novo synthesis are used by bacteria to produce PHA from different carbon sources like fatty acids and sugars, respectively. There are various factors affecting the 3HHx molar composition of P(3HB-co-3HHx), like PhaCs, the engineering of PhaCs, and the metabolic engineering of strains. It is crucial to control the 3HHx molar composition in the P(3HB-co-3HHx) as it will affect its properties and applications in different fields.
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Sustainable applications of polyhydroxyalkanoates in various fields: A critical review. Int J Biol Macromol 2022; 221:1184-1201. [PMID: 36113591 DOI: 10.1016/j.ijbiomac.2022.09.098] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 09/06/2022] [Accepted: 09/10/2022] [Indexed: 01/23/2023]
Abstract
PHA is one of the most promising candidates in bio-polymer family which is biodegradable and environment-friendly in nature. In recent years, it has been applied as a biodegradable alternative for petroleum-based plastic across different domains. In literature, several research groups have scrutinised the biocompatibility and biodegradability of PHA in both in vivo settings as well as in in vitro conditions. Microbial yield polyhydroxyalkanoates (PHAs) are promoted at present as biodegradable plastics. On the other hand, only a limited number of products is being commercially manufactured out of PHAs (e.g., bottles). A succession of microbes (prokaryotes in addition to eukaryotes) has been identified as potential candidates that can disintegrate PHAs. These materials have been successfully employed in packaging industry, medical devices and implants, moulded goods, paper coatings, adhesives, performance additives, mulch films, non-woven fabrics, etc. The present paper reviews and focuses on the potential applications of PHA and its derivatives in different industries.
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Study of the production of poly(hydroxybutyrate- co-hydroxyhexanoate) and poly(hydroxybutyrate- co-hydroxyvalerate- co-hydroxyhexanoate) in Rhodospirillum rubrum. Appl Environ Microbiol 2022; 88:e0158621. [PMID: 35080906 DOI: 10.1128/aem.01586-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Poly(hydroxybutyrate-co-hydroxyhexanoate) (P(HB-co-HHx)) and poly(hydroxybutyrate-co-hydroxyvalerate-co-hydroxyhexanoate) P(HB-co-HV-co-HHx) demonstrate interesting mechanical and thermal properties as well as excellent biocompatibility making them suitable for multiple applications and notably biomedical purposes. The production of such polymer was described in Rhodospirillum rubrum (Rs. rubrum), a purple non-sulfur bacteria in a nutrient-lacking environment where the HHx synthesis is triggered by the presence of hexanoate in the medium. However, the production of P(HB-co-HHx) under nutrient-balanced growth conditions has not been described so far in Rs. rubrum and the assimilation of hexanoate is poorly documented. In this study, we demonstrate using proteomic analysis and mutant fitness assay, that hexanoate assimilation involve β-oxidation and the ethylmalonyl-CoA (EMC) and methylbutanoyl-CoA (MBC) pathways, both being anaplerotic pathways already described in Rs. rubrum. Polyhydroxyalkanoate (PHA) production is likely to involve the de novo fatty acid synthesis pathway. Concerning the polymer composition, HB is the main component of the polymer, probably as acetyl-CoA and butyryl-CoA are intermediates of hexanoate assimilation pathways. When no essential nutrient is lacking in the medium, the synthesis of PHA seems to help maintain the redox balance of the cell. In this framework, we showed that the fixation of CO2 is required to sustain the growth. An increase in the proportion of HHx in the polymer was observed when redox stress was engendered in the cell under bicarbonate limiting growth conditions. The addition of isoleucine or valerate in the medium also increased the HHx content of the polymer and allowed the production of a terpolymer of P(HB-co-HV-co-HHx). Importance The use of purple bacteria, which can assimilate volatile fatty acids for biotechnological applications has risen since they reduce the production costs of added-value compounds such as PHA. P(HB-co-HHx) and P(HB-co-HV-co-HHx) have demonstrated interesting properties notably for biomedical application. In a nutrient-lacking environment, Rs. rubrum is known to synthesize such polymer when hexanoate is used as carbon source. However, their production in non-nutrient lacking growth conditions has not been described so far in Rs. rubrum and the assimilation of hexanoate is poorly documented. As the carbon source and its assimilation directly impact the polymer composition, we studied under non-nutrient lacking growth conditions, the assimilation path of hexanoate and PHA production in Rs. rubrum. Proteomic analysis and mutant fitness assay allowed to explain PHA production and composition. Increase in HHx content of the polymer and production of P(HB-co-HV-co-HHx) was possible using the knowledge gained on metabolism under hexanoate growth conditions.
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Kaniuk Ł, Stachewicz U. Development and Advantages of Biodegradable PHA Polymers Based on Electrospun PHBV Fibers for Tissue Engineering and Other Biomedical Applications. ACS Biomater Sci Eng 2021; 7:5339-5362. [PMID: 34649426 PMCID: PMC8672356 DOI: 10.1021/acsbiomaterials.1c00757] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
![]()
Biodegradable polymeric
biomaterials offer a significant advantage
in disposable or fast-consuming products in medical applications.
Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)
is an example of a polyhydroxyalkanoate (PHA), i.e., one group of
natural polyesters that are byproducts of reactions taking place in
microorganisms in conditions with an excess carbon source. PHA polymers
are a promising material for the production of everyday materials
and biomedical applications. Due to the high number of monomers in
the group, PHAs permit modifications enabling the production of copolymers
of different compositions and with different proportions of individual
monomers. In order to change and improve the properties of polymer
fibers, PHAs are combined with either other natural and synthetic
polymers or additives of inorganic phases. Importantly, electrospun
PHBV fibers and mats showed an enormous potential in both the medical
field (tissue engineering scaffolds, plasters, wound healing, drug
delivery systems) and industrial applications (filter systems, food
packaging). This Review summarizes the current state of the art in
processing PHBV, especially by electrospinning, its degradation processes,
and biocompatibility studies, starting from a general introduction
to the PHA group of polymers.
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Affiliation(s)
- Łukasz Kaniuk
- AGH University of Science and Technology, Faculty of Metals Engineering and Industrial Computer Science, al. A. Mickiewicza 30, 30-059 Kraków, Poland
| | - Urszula Stachewicz
- AGH University of Science and Technology, Faculty of Metals Engineering and Industrial Computer Science, al. A. Mickiewicza 30, 30-059 Kraków, Poland
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Ansari S, Sami N, Yasin D, Ahmad N, Fatma T. Biomedical applications of environmental friendly poly-hydroxyalkanoates. Int J Biol Macromol 2021; 183:549-563. [PMID: 33932421 DOI: 10.1016/j.ijbiomac.2021.04.171] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 04/26/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023]
Abstract
Biological polyesters of hydroxyacids are known as polyhydroxyalkanoates (PHA). They have proved to be an alternative, environmentally friendly and attractive candidate for the replacement of petroleum-based plastics in many applications. Many bacteria synthesize these compounds as an intracellular carbon and energy compound usually under unbalanced growth conditions. Biodegradability and biocompatibility of different PHA has been studied in cell culture systems or in an animal host during the last few decades. Such investigations have proposed that PHA can be used as biomaterials for applications in conventional medical devices such as sutures, patches, meshes, implants, and tissue engineering scaffolds as well. Moreover, findings related to encapsulation capability and degradation kinetics of some PHA polymers has paved their way for development of controlled drug delivery systems. The present review discusses about bio-plastics, their characteristics, examines the key findings and recent advances highlighting the usage of bio-plastics in different medical devices. The patents concerning to PHA application in biomedical field have been also enlisted that will provide a brief overview of the status of research in bio-plastic. This would help medical researchers and practitioners to replace the synthetic plastics aids that are currently being used. Simultaneously, it could also prove to be a strong step in reducing the plastic pollution that surged abruptly due to the COVID-19 medical waste.
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Affiliation(s)
- Sabbir Ansari
- Cyanobacterial Biotechnology Laboratory, Department of Biosciences, Jamia Millia Islamia (Central University), New Delhi 110025, India
| | - Neha Sami
- Cyanobacterial Biotechnology Laboratory, Department of Biosciences, Jamia Millia Islamia (Central University), New Delhi 110025, India
| | - Durdana Yasin
- Cyanobacterial Biotechnology Laboratory, Department of Biosciences, Jamia Millia Islamia (Central University), New Delhi 110025, India
| | - Nazia Ahmad
- Cyanobacterial Biotechnology Laboratory, Department of Biosciences, Jamia Millia Islamia (Central University), New Delhi 110025, India
| | - Tasneem Fatma
- Cyanobacterial Biotechnology Laboratory, Department of Biosciences, Jamia Millia Islamia (Central University), New Delhi 110025, India.
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Meléndez-Rodríguez B, Torres-Giner S, Reis MAM, Silva F, Matos M, Cabedo L, Lagarón JM. Blends of Poly(3-Hydroxybutyrate- co-3-Hydroxyvalerate) with Fruit Pulp Biowaste Derived Poly(3-Hydroxybutyrate- co-3-Hydroxyvalerate- co-3-Hydroxyhexanoate) for Organic Recycling Food Packaging. Polymers (Basel) 2021; 13:1155. [PMID: 33916564 PMCID: PMC8038484 DOI: 10.3390/polym13071155] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 03/25/2021] [Accepted: 03/26/2021] [Indexed: 11/17/2022] Open
Abstract
In the present study, a new poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) [P(3HB-co-3HV-co-3HHx)] terpolyester with approximately 68 mol% of 3-hydroxybutyrate (3HB), 17 mol% of 3-hydroxyvalerate (3HV), and 15 mol% of 3-hydroxyhexanoate (3HHx) was obtained via the mixed microbial culture (MMC) technology using fruit pulps as feedstock, a processing by-product of the juice industry. After extraction and purification performed in a single step, the P(3HB-co-3HV-co-3HHx) powder was melt-mixed, for the first time, in contents of 10, 25, and 50 wt% with commercial poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). Thereafter, the resultant doughs were thermo-compressed to obtain highly miscible films with good optical properties, which can be of interest in rigid and semirigid organic recyclable food packaging applications. The results showed that the developed blends exhibited a progressively lower melting enthalpy with increasing the incorporation of P(3HB-co-3HV-co-3HHx), but retained the PHB crystalline morphology, albeit with an inferred lower crystalline density. Moreover, all the melt-mixed blends were thermally stable up to nearly 240 °C. As the content of terpolymer increased in the blends, the mechanical response of their films showed a brittle-to-ductile transition. On the other hand, the permeabilities to water vapor, oxygen, and, more notably, limonene were seen to increase. On the overall, this study demonstrates the value of using industrial biowaste derived P(3HB-co-3HV-co-3HHx) terpolyesters as potentially cost-effective and sustainable plasticizing additives to balance the physical properties of organic recyclable polyhydroxyalkanoate (PHA)-based food packaging materials.
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Affiliation(s)
- Beatriz Meléndez-Rodríguez
- Novel Materials and Nanotechnology Group, Institute of Agrochemistry and Food Technology (IATA), Spanish Council for Scientific Research (CSIC), Calle Catedrático Agustín Escardino Benlloch 7, 46980 Paterna, Spain; (B.M.-R.); (S.T.-G.)
| | - Sergio Torres-Giner
- Novel Materials and Nanotechnology Group, Institute of Agrochemistry and Food Technology (IATA), Spanish Council for Scientific Research (CSIC), Calle Catedrático Agustín Escardino Benlloch 7, 46980 Paterna, Spain; (B.M.-R.); (S.T.-G.)
| | - Maria A. M. Reis
- UCIBIO-REQUIMTE-Applied Molecular Biosciences Unit, Chemistry Department, Faculty of Sciences and Technology, New University of Lisbon, 1099-085 Lisbon, Portugal; (M.A.M.R.); (F.S.); (M.M.)
| | - Fernando Silva
- UCIBIO-REQUIMTE-Applied Molecular Biosciences Unit, Chemistry Department, Faculty of Sciences and Technology, New University of Lisbon, 1099-085 Lisbon, Portugal; (M.A.M.R.); (F.S.); (M.M.)
| | - Mariana Matos
- UCIBIO-REQUIMTE-Applied Molecular Biosciences Unit, Chemistry Department, Faculty of Sciences and Technology, New University of Lisbon, 1099-085 Lisbon, Portugal; (M.A.M.R.); (F.S.); (M.M.)
| | - Luis Cabedo
- Polymers and Advanced Materials Group (PIMA), Universitat Jaume I (UJI), 12071 Castellón, Spain;
| | - José María Lagarón
- Novel Materials and Nanotechnology Group, Institute of Agrochemistry and Food Technology (IATA), Spanish Council for Scientific Research (CSIC), Calle Catedrático Agustín Escardino Benlloch 7, 46980 Paterna, Spain; (B.M.-R.); (S.T.-G.)
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Turco R, Santagata G, Corrado I, Pezzella C, Di Serio M. In vivo and Post-synthesis Strategies to Enhance the Properties of PHB-Based Materials: A Review. Front Bioeng Biotechnol 2021; 8:619266. [PMID: 33585417 PMCID: PMC7874203 DOI: 10.3389/fbioe.2020.619266] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 11/30/2020] [Indexed: 12/13/2022] Open
Abstract
The transition toward "green" alternatives to petroleum-based plastics is driven by the need for "drop-in" replacement materials able to combine characteristics of existing plastics with biodegradability and renewability features. Promising alternatives are the polyhydroxyalkanoates (PHAs), microbial biodegradable polyesters produced by a wide range of microorganisms as carbon, energy, and redox storage material, displaying properties very close to fossil-fuel-derived polyolefins. Among PHAs, polyhydroxybutyrate (PHB) is by far the most well-studied polymer. PHB is a thermoplastic polyester, with very narrow processability window, due to very low resistance to thermal degradation. Since the melting temperature of PHB is around 170-180°C, the processing temperature should be at least 180-190°C. The thermal degradation of PHB at these temperatures proceeds very quickly, causing a rapid decrease in its molecular weight. Moreover, due to its high crystallinity, PHB is stiff and brittle resulting in very poor mechanical properties with low extension at break, which limits its range of application. A further limit to the effective exploitation of these polymers is related to their production costs, which is mostly affected by the costs of the starting feedstocks. Since the first identification of PHB, researchers have faced these issues, and several strategies to improve the processability and reduce brittleness of this polymer have been developed. These approaches range from the in vivo synthesis of PHA copolymers, to the enhancement of post-synthesis PHB-based material performances, thus the addition of additives and plasticizers, acting on the crystallization process as well as on polymer glass transition temperature. In addition, reactive polymer blending with other bio-based polymers represents a versatile approach to modulate polymer properties while preserving its biodegradability. This review examines the state of the art of PHA processing, shedding light on the green and cost-effective tailored strategies aimed at modulating and optimizing polymer performances. Pioneering examples in this field will be examined, and prospects and challenges for their exploitation will be presented. Furthermore, since the establishment of a PHA-based industry passes through the designing of cost-competitive production processes, this review will inspect reported examples assessing this economic aspect, examining the most recent progresses toward process sustainability.
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Affiliation(s)
- Rosa Turco
- Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Naples, Italy
| | - Gabriella Santagata
- Institute for Polymers, Composites and Biomaterials, National Council of Research, Pozzuoli, Italy
| | - Iolanda Corrado
- Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Naples, Italy
| | - Cinzia Pezzella
- Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy
| | - Martino Di Serio
- Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Naples, Italy
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Carriers based on poly-3-hydroxyalkanoates containing nanomagnetite to trigger hormone release. Int J Biol Macromol 2020; 166:448-458. [PMID: 33127545 DOI: 10.1016/j.ijbiomac.2020.10.203] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 10/17/2020] [Accepted: 10/22/2020] [Indexed: 02/08/2023]
Abstract
Poly-3-hydroxybutyrate (P(3HB)) and poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (P(3HB-co-3HHx)) are biocompatible and bioabsorbable biopolymers produced by different bacteria with potential for drug delivery in thermo-responsive magnetic microcarriers. Microparticles of P(3HB) and P(3HB-co-3HHx), with 5.85% mol of 3HHx, produced by Burkholderia sacchari, containing nanomagnetite (nM) and lipophilic hormone were prepared by simple emulsion (oil/water) technique leading to progesterone (Pg) encapsulation efficiency higher than 70% and magnetite loads of 3.1 and 2.3% (w/w) for P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg, respectively. These formulations were characterized by Infrared spectroscopy, X-ray diffraction, Thermal gravimetric analysis and Electron microscopy (TEM, SEM) techniques. The P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg microparticles presented spherical geometry with wrinkled surfaces and average size between 2 and 40 μm for 90% of the microparticles. The release profiles of the P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg formulations showed a hormone release trigger (6.9 and 11.1%, respectively) effect induced by oscillating external magnetic field (0.2 T), after 72 h. Progesterone release in non-magnetic tests with P(3HB-co-3HHx)/nM/Pg revealed a slight increment (5.6%) in relation to P(3HB)/nM/Pg. The experimental release of the P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg samples presented a good agreement with Higuchi model. The 3HHx comonomer content improves the hormone release of the P(3HB-co-3HHx)/nM/Pg formulation with potential for application to synchronize the estrous cycle.
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Frone AN, Nicolae CA, Eremia MC, Tofan V, Ghiurea M, Chiulan I, Radu E, Damian CM, Panaitescu DM. Low Molecular Weight and Polymeric Modifiers as Toughening Agents in Poly(3-Hydroxybutyrate) Films. Polymers (Basel) 2020; 12:E2446. [PMID: 33105812 PMCID: PMC7716241 DOI: 10.3390/polym12112446] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 10/20/2020] [Accepted: 10/20/2020] [Indexed: 01/10/2023] Open
Abstract
The inherent brittleness of poly(3-hydroxybutyrate) (PHB) prevents its use as a substitute of petroleum-based polymers. Low molecular weight plasticizers, such as tributyl 2-acetyl citrate (TAC), cannot properly solve this issue. Herein, PHB films were obtained using a biosynthesized poly(3-hydroxyoctanoate) (PHO) and a commercially available TAC as toughening agents. The use of TAC strongly decreased the PHB thermal stability up to 200 °C due to the loss of low boiling point plasticizer, while minor weight loss was noticed at this temperature for the PHB-PHO blend. Both agents shifted the glass transition temperature of PHB to a lower temperature, the effect being more pronounced for TAC. The elongation at break of PHB increased by 700% after PHO addition and by only 185% in the case of TAC; this demonstrates an important toughening effect of the polymeric modifier. Migration of TAC to the upper surface of the films and no sign of migration in the case of PHO were highlighted by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) results. In vitro biocompatibility tests showed that all the PHB films are non-toxic towards L929 cells and have no proinflammatory immune response. The use of PHO as a toughening agent in PHB represents an attractive solution to its brittleness in the case of packaging and biomedical applications while conserving its biodegradability and biocompatibility.
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Affiliation(s)
- Adriana Nicoleta Frone
- Polymer Department, National Institute for R&D in Chemistry and Petrochemistry ICECHIM, 202 Splaiul Independentei, 060021 Bucharest, Romania; (C.A.N.); (M.G.); (I.C.); (E.R.)
| | - Cristian Andi Nicolae
- Polymer Department, National Institute for R&D in Chemistry and Petrochemistry ICECHIM, 202 Splaiul Independentei, 060021 Bucharest, Romania; (C.A.N.); (M.G.); (I.C.); (E.R.)
| | - Mihaela Carmen Eremia
- National Institute for Chemical Pharmaceutical Research and Development ICCF, 112 Calea Vitan, 031299 Bucharest, Romania;
| | - Vlad Tofan
- Cantacuzino National Institute of R&D for Microbiology and Immunology, 103 Splaiul Independentei, 050096 Bucharest, Romania;
| | - Marius Ghiurea
- Polymer Department, National Institute for R&D in Chemistry and Petrochemistry ICECHIM, 202 Splaiul Independentei, 060021 Bucharest, Romania; (C.A.N.); (M.G.); (I.C.); (E.R.)
| | - Ioana Chiulan
- Polymer Department, National Institute for R&D in Chemistry and Petrochemistry ICECHIM, 202 Splaiul Independentei, 060021 Bucharest, Romania; (C.A.N.); (M.G.); (I.C.); (E.R.)
| | - Elena Radu
- Polymer Department, National Institute for R&D in Chemistry and Petrochemistry ICECHIM, 202 Splaiul Independentei, 060021 Bucharest, Romania; (C.A.N.); (M.G.); (I.C.); (E.R.)
| | - Celina Maria Damian
- Advanced Polymer Materials Group, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1-7 Gheorghe Polizu, 011061 Bucharest, Romania;
| | - Denis Mihaela Panaitescu
- Polymer Department, National Institute for R&D in Chemistry and Petrochemistry ICECHIM, 202 Splaiul Independentei, 060021 Bucharest, Romania; (C.A.N.); (M.G.); (I.C.); (E.R.)
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14
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Ward AC, Dubey P, Basnett P, Lika G, Newman G, Corrigan DK, Russell C, Kim J, Chakrabarty S, Connolly P, Roy I. Toward a Closed Loop, Integrated Biocompatible Biopolymer Wound Dressing Patch for Detection and Prevention of Chronic Wound Infections. Front Bioeng Biotechnol 2020; 8:1039. [PMID: 32984295 PMCID: PMC7493637 DOI: 10.3389/fbioe.2020.01039] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 08/11/2020] [Indexed: 01/22/2023] Open
Abstract
Chronic wound infections represent a significant burden to healthcare providers globally. Often, chronic wound healing is impeded by the presence of infection within the wound or wound bed. This can result in an increased healing time, healthcare cost and poor patient outcomes. Thus, there is a need for dressings that help the wound heal, in combination with early detection of wound infections to support prompt treatment. In this study, we demonstrate a novel, biocompatible wound dressing material, based on Polyhydroxyalkanoates, doped with graphene platelets, which can be used as an electrochemical sensing substrate for the detection of a common wound pathogen, Pseudomonas aeruginosa. Through the detection of the redox active secondary metabolite, pyocyanin, we demonstrate that a dressing can be produced that will detect the presence of pyocyanin across clinically relevant concentrations. Furthermore, we show that this sensor can be used to identify the presence of pyocyanin in a culture of P. aeruginosa. Overall, the sensor substrate presented in this paper represents the first step toward a new dressing with the capacity to promote wound healing, detect the presence of infection and release antimicrobial drugs, on demand, to optimized healing.
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Affiliation(s)
- Andrew C. Ward
- Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, United Kingdom
| | - Prachi Dubey
- School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, London, United Kingdom
| | - Pooja Basnett
- School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, London, United Kingdom
| | - Granit Lika
- School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, London, United Kingdom
| | - Gwenyth Newman
- Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, United Kingdom
| | - Damion K. Corrigan
- Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, United Kingdom
| | | | - Jongrae Kim
- School of Mechanical Engineering, Faculty of Engineering, University of Leeds, Leeds, United Kingdom
| | - Samit Chakrabarty
- School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
| | - Patricia Connolly
- Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, United Kingdom
| | - Ipsita Roy
- Department of Materials Science and Engineering, Faculty of Engineering, The University of Sheffield, Sheffield, United Kingdom
- *Correspondence: Ipsita Roy,
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15
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Ba K, Wei X, Ni D, Li N, Du T, Wang X, Pan W. Chondrocyte Co-cultures with the Stromal Vascular Fraction of Adipose Tissue in Polyhydroxybutyrate/Poly-(hydroxybutyrate-co-hydroxyhexanoate) Scaffolds: Evaluation of Cartilage Repair in Rabbit. Cell Transplant 2019; 28:1432-1438. [PMID: 31337228 PMCID: PMC6802145 DOI: 10.1177/0963689719861275] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Chondral defects are challenging to repair because of the poor self-healing capacity of
articular cartilage. The aim of this study was to compare and investigate the cartilage
regeneration of stromal vascular fraction (SVF) cells and adipose-derived stem cells
(ASCs) co-cultured with chondrocytes seeding on scaffolds composed of polyhydroxybutyrate
(PHB)/poly-(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx). In this study, the cellular
morphologies and proliferation capabilities on scaffolds were evaluated. Next, scaffolds
with 1:1 co-culture of ASCs/SVF and chondrocytes were implanted into the full-thickness
cartilage defects in rabbit knee for 10 weeks. Cells seeded on the scaffolds showed better
adhesion, migration, and proliferation in vitro. Importantly, implantation with scaffolds
with SVF and chondrocytes revealed more desirable in vivo healing outcomes. Our results
illustrate a one-step surgical procedure for the regeneration of focal cartilage defects
using a mixture of SVF from adipose tissue and uncultured chondrocytes.
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Affiliation(s)
- Kai Ba
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.,* Both the authors contributed equally to this article
| | - Xueqin Wei
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.,* Both the authors contributed equally to this article
| | - Duan Ni
- Department of Emergency Medicine, Armed Police Corps Hospital of Henan, Zhengzhou, Henan, People's Republic of China
| | - Na Li
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Tianfeng Du
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Xinbo Wang
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Wenting Pan
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
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16
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Grigore ME, Grigorescu RM, Iancu L, Ion RM, Zaharia C, Andrei ER. Methods of synthesis, properties and biomedical applications of polyhydroxyalkanoates: a review. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2019; 30:695-712. [DOI: 10.1080/09205063.2019.1605866] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Mădălina Elena Grigore
- "Evaluation and Conservation of Cultural Heritage” Research Group, National Institute for Research and Development in Chemistry and Petrochemistry, ICECHIM, Bucharest, Romania
| | - Ramona Marina Grigorescu
- "Evaluation and Conservation of Cultural Heritage” Research Group, National Institute for Research and Development in Chemistry and Petrochemistry, ICECHIM, Bucharest, Romania
| | - Lorena Iancu
- "Evaluation and Conservation of Cultural Heritage” Research Group, National Institute for Research and Development in Chemistry and Petrochemistry, ICECHIM, Bucharest, Romania
| | - Rodica-Mariana Ion
- "Evaluation and Conservation of Cultural Heritage” Research Group, National Institute for Research and Development in Chemistry and Petrochemistry, ICECHIM, Bucharest, Romania
- Valahia University, Materials Engineering Department, 13th Aleey Sinaia, Targoviste, Romania
| | - Cătălin Zaharia
- Advanced Polymer Materials Group, University Politehnica of Bucharest, Bucharest, Romania
| | - Elena Ramona Andrei
- "Evaluation and Conservation of Cultural Heritage” Research Group, National Institute for Research and Development in Chemistry and Petrochemistry, ICECHIM, Bucharest, Romania
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17
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Luo Z, Jiang L, Ding C, Hu B, Loh XJ, Li Z, Wu Y. Surfactant Free Delivery of Docetaxel by Poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate]-Based Polymeric Micelles for Effective Melanoma Treatments. Adv Healthc Mater 2018; 7:e1801221. [PMID: 30398017 DOI: 10.1002/adhm.201801221] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 10/23/2018] [Indexed: 12/13/2022]
Abstract
Docetaxel (DTX) is a new semisynthetic chemical in the taxoid family and serves a wide spectrum of chemotherapeutics. Current commercial formulation of DTX is based on the addition of the nonionic surfactants (i.e., ethanol and Tween 80), which are reported to cause severe hemolysis, hypersensitivity reactions, or neurotoxic toxicity and greatly hinders patient tolerance or compliance. In this report, a novel low-toxic, biodegradable, and amphiphilic poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate] (PHBHx)-based polyurethane (a copolymer made of hydrophobic PHBHx with biocompatible D-3-hydroxybutyric acid as degradation product, thermosensitive polypropylene glycol (PPG), and hydrophilic polyethylene glycol (PEG) segments) with nanosized micelle formation ability to encapsulate DTX, as a surfactant free formulation, is reported. Interestingly, this DTX-loaded poly(PHBHx/PEG/PPG urethane) micelle formulation with >90% drug loading efficiency shows significantly improved DTX solubility in aqueous medium, reduced hemolysis for better blood compatibility, and increased drug uptake in A375 melanoma cells, which provides the possibility of systematic delivery of DTX. As a proof-of-concept, an A375 melanoma xenograft mouse model is established to verify the therapeutic effect of this DTX-loaded poly(PHBHx/PEG/PPG urethane) micelle formulation, indicating the promising application of PHBHx-based polymeric nanosized micelle as a surfactant free formulation of chemotherapeutics which might greatly be beneficial for controllable delivery of pharmaceutics and cancer therapy.
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Affiliation(s)
- Zheng Luo
- Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress BiologySchool of Pharmaceutical SciencesXiamen University Xiamen 361102 P. R. China
| | - Lu Jiang
- Institute of Materials Research and EngineeringA*STAR (Agency for Science, Technology and Research) 2 Fusionopolis Way, Innovis, #08‐03 Singapore 138634 Singapore
| | - Chizhu Ding
- College of ScienceHuazhong Agricultural University Wuhan 430074 P. R. China
| | - Benhui Hu
- School of Biomedical Engineering and InformaticsNanjing Medical University Nanjing 211166 P. R. China
| | - Xian Jun Loh
- Institute of Materials Research and EngineeringA*STAR (Agency for Science, Technology and Research) 2 Fusionopolis Way, Innovis, #08‐03 Singapore 138634 Singapore
| | - Zibiao Li
- Institute of Materials Research and EngineeringA*STAR (Agency for Science, Technology and Research) 2 Fusionopolis Way, Innovis, #08‐03 Singapore 138634 Singapore
| | - Yun‐Long Wu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress BiologySchool of Pharmaceutical SciencesXiamen University Xiamen 361102 P. R. China
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18
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Ye H, Zhang K, Kai D, Li Z, Loh XJ. Polyester elastomers for soft tissue engineering. Chem Soc Rev 2018; 47:4545-4580. [PMID: 29722412 DOI: 10.1039/c8cs00161h] [Citation(s) in RCA: 135] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Polyester elastomers are soft, biodegradable and biocompatible and are commonly used in various biomedical applications, especially in tissue engineering. These synthetic polyesters can be easily fabricated using various techniques such as solvent casting, particle leaching, molding, electrospinning, 3-dimensional printing, photolithography, microablation etc. A large proportion of tissue engineering research efforts have focused on the use of allografts, decellularized animal scaffolds or other biological materials as scaffolds, but they face the major concern of triggering immunological responses from the host, on top of other issues. This review paper will introduce the recent developments in elastomeric polyesters, their synthesis and fabrication techniques, as well as their application in the biomedical field, focusing primarily on tissue engineering in ophthalmology, cardiac and vascular systems. Some of the commercial and near-commercial polyesters used in these tissue engineering fields will also be described.
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Affiliation(s)
- Hongye Ye
- Institute of Materials Research and Engineering (IMRE), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Singapore.
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19
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Rajaratanam DD, Ariffin H, Hassan MA, Nik Abd Rahman NMA, Nishida H. In vitro cytotoxicity of superheated steam hydrolyzed oligo((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) and characteristics of its blend with poly(L-lactic acid) for biomaterial applications. PLoS One 2018; 13:e0199742. [PMID: 29944726 PMCID: PMC6019698 DOI: 10.1371/journal.pone.0199742] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2018] [Accepted: 06/13/2018] [Indexed: 11/19/2022] Open
Abstract
In order to clarify the in vitro cytotoxicity effect of superheated steam (SHS) treated poly((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) (PHBHHx) for biomaterial applications, SHS-treated PHBHHx oligoester samples: P(HB-co-6%-HHx) and P(HB-co-11%-HHx) with low and high percentages of unsaturated chain ends were evaluated for their cytotoxicity effects toward the growth of mouse fibroblast cell line NIH 3T3. From the results obtained after 24 and 48 h of the growth test, the SHS-treated PHBHHx oligoesters were found to be nontoxic to the growth of mouse fibroblast NIH 3T3 cell line with cell viability percentages of more than 95%. In order to serve as a potential resorbable medical suture, PHBHHx oligoesters were blended with poly(L-lactic acid) (PLLA) with a weight ratio of PHBHHx oligoester/PLLA = 20:80 (wt/wt) to improve mechanical properties of PHBHHx oligoesters. The PHBHHx oligoesters/PLLA blend films were evaluated for their thermal, mechanical, and surface wetting properties. Thermal properties of the blend films suggested a good compatibility between PHBHHx oligoesters and PLLA components. Mechanical properties of the blend films were determined to be close enough to a desirable strength range of medical sutures. Moreover, contact angle range of 65 < θ < 70° for the blend samples could provide desirable cell adhesion when used as biomaterials. Therefore, the blend of SHS-treated PHBHHx oligoesters and PLLA would be an ideal choice to be used as biomedical materials.
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Affiliation(s)
- Dhurga Devi Rajaratanam
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Malaysia
- Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Hibikino, Wakamatsu, Kitakyushu, Fukuoka, Japan
| | - Hidayah Ariffin
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Malaysia
- Institute of Tropical Forestry and Forest Products (INTROP), Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia
| | - Mohd Ali Hassan
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Malaysia
| | - Nik Mohd Afizan Nik Abd Rahman
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Malaysia
| | - Haruo Nishida
- Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Hibikino, Wakamatsu, Kitakyushu, Fukuoka, Japan
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20
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Ray S, Kalia VC. Biomedical Applications of Polyhydroxyalkanoates. Indian J Microbiol 2017; 57:261-269. [PMID: 28904409 PMCID: PMC5574769 DOI: 10.1007/s12088-017-0651-7] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 04/20/2017] [Indexed: 12/24/2022] Open
Abstract
Polyhydroxyalkanoates (PHA) are produced by a large number of microbes under stress conditions such as high carbon (C) availability and limitations of nutrients such as nitrogen, potassium, phosphorus, magnesium, and oxygen. Here, microbes store C as granules of PHAs-energy reservoir. PHAs have properties, which are quite similar to those of synthetic plastics. The unique properties, which make them desirable materials for biomedical applications is their biodegradability, biocompatibility, and non-toxicity. PHAs have been found suitable for various medical applications: biocontrol agents, drug carriers, biodegradable implants, tissue engineering, memory enhancers, and anticancer agents.
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Affiliation(s)
- Subhasree Ray
- Microbial Biotechnology and Genomics, CSIR - Institute of Genomics and Integrative Biology (IGIB), Delhi University Campus, Mall Road, Delhi, 110007 India
- Academy of Scientific and Innovative Research (AcSIR), 2, Rafi Marg, Anusandhan Bhawan, New Delhi, 110001 India
| | - Vipin Chandra Kalia
- Microbial Biotechnology and Genomics, CSIR - Institute of Genomics and Integrative Biology (IGIB), Delhi University Campus, Mall Road, Delhi, 110007 India
- Academy of Scientific and Innovative Research (AcSIR), 2, Rafi Marg, Anusandhan Bhawan, New Delhi, 110001 India
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21
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Lim J, You M, Li J, Li Z. Emerging bone tissue engineering via Polyhydroxyalkanoate (PHA)-based scaffolds. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2017. [PMID: 28629097 DOI: 10.1016/j.msec.2017.05.132] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Polyhydroxyalkanoates (PHAs) are a class of biodegradable polymers derived from microorganisms. On top of their biodegradability and biocompatibility, different PHA types can contribute to varying mechanical and chemical properties. This has led to increasing attention to the use of PHAs in numerous biomedical applications over the past few decades. Bone tissue engineering refers to the regeneration of new bone through providing mechanical support while inducing cell growth on the PHA scaffolds having a porous structure for tissue regeneration. This review first introduces the various properties PHA scaffold that make them suitable for bone tissue engineering such as biocompatibility, biodegradability, mechanical properties as well as vascularization. The typical fabrication techniques of PHA scaffolds including electrospinning, salt-leaching and solution casting are further discussed, followed by the relatively new technology of using 3D printing in PHA scaffold fabrication. Finally, the recent progress of using different types of PHAs scaffold in bone tissue engineering applications are summarized in intrinsic PHA/blends forms or as composites with other polymeric or inorganic hybrid materials.
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Affiliation(s)
- Janice Lim
- Department of Chemical & Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore
| | - Mingliang You
- Cancer Science Institute of Singapore, National University of Singapore, 14 medical drive, Singapore 117599, Singapore
| | - Jian Li
- Center for translational medicine research and development, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Guangdong 518055, China
| | - Zibiao Li
- Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Innovis, #08-03, Singapore 138634, Singapore.
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22
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Production and characterization of PHB from a novel isolate Comamonas sp. from a dairy effluent sample and its application in cell culture. Biochem Eng J 2015. [DOI: 10.1016/j.bej.2015.05.012] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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23
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24
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Biazar E. Polyhydroxyalkanoates as Potential Biomaterials for Neural Tissue Regeneration. INT J POLYM MATER PO 2014. [DOI: 10.1080/00914037.2014.886227] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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25
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Li Y, Shao W, Jin S, Xu T, Jiang X, Yang S, Wang Z, Dai J, Wu Q. Microgrooved poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) affects the phenotype of vascular smooth muscle cells through let-7a-involved regulation of actin dynamics. Biotechnol Lett 2014; 36:2125-33. [DOI: 10.1007/s10529-014-1562-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Accepted: 05/23/2014] [Indexed: 12/27/2022]
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26
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Chang HM, Wang ZH, Luo HN, Xu M, Ren XY, Zheng GX, Wu BJ, Zhang XH, Lu XY, Chen F, Jing XH, Wang L. Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)-based scaffolds for tissue engineering. ACTA ACUST UNITED AC 2014; 47:533-9. [PMID: 25003631 PMCID: PMC4123831 DOI: 10.1590/1414-431x20143930] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Accepted: 03/12/2014] [Indexed: 01/18/2023]
Abstract
Development and selection of an ideal scaffold is of importance for tissue engineering. Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is a biocompatible bioresorbable copolymer that belongs to the polyhydroxyalkanoate family. Because of its good biocompatibility, PHBHHx has been widely used as a cell scaffold for tissue engineering. This review focuses on the utilization of PHBHHx-based scaffolds in tissue engineering. Advances in the preparation, modification, and application of PHBHHx scaffolds are discussed.
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Affiliation(s)
- H M Chang
- Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Xi'an Medical University, Xi'an, China
| | - Z H Wang
- Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiaotong University, Xi'an, China
| | - H N Luo
- Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiaotong University, Xi'an, China
| | - M Xu
- Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiaotong University, Xi'an, China
| | - X Y Ren
- Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiaotong University, Xi'an, China
| | - G X Zheng
- Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiaotong University, Xi'an, China
| | - B J Wu
- Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiaotong University, Xi'an, China
| | - X H Zhang
- Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiaotong University, Xi'an, China
| | - X Y Lu
- School of Life Science and Technology of Xi'an Jiaotong University, Xi'an, China
| | - F Chen
- Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiaotong University, Xi'an, China
| | - X H Jing
- Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiaotong University, Xi'an, China
| | - L Wang
- Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiaotong University, Xi'an, China
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Sakar M, Korkusuz P, Demirbilek M, Cetinkaya DU, Arslan S, Denkbaş EB, Temuçin ÇM, Bilgiç E, Hazer DB, Bozkurt G. The effect of poly(3-hydroxybutyrate-co-3- hydroxyhexanoate) (PHBHHx) and human mesenchymal stem cell (hMSC) on axonal regeneration in experimental sciatic nerve damage. Int J Neurosci 2014; 124:685-96. [PMID: 24350993 DOI: 10.3109/00207454.2013.876636] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
This study is designed to evaluate the treatment effect of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and human mesenchymal stem cells (hMSC) on axonal regeneration in experimental rat sciatic nerve damage, and compare the results of this modality with autologous nerve grafting. In Spraque-Dawley albino rats, 10-mm-long experimental nerve gaps were created. Three groups were constituted, the gap was repaired with autologous nerve graft (autograft group), PHBHHx nerve graft alone (PHBHHx alone group), and PHBHHx nerve graft with hMSCs inside (PHBHHx with hMSC group), respectively. The results were evaluated with functional recovery, electrophysiological evaluation, and histological evaluation either with light microscopy and transmission electron microscopy for axonal regeneration and myelin formation. In functional evaluation, autograft and PHBHHx with hMSC groups showed functional improvement with time, whereas PHBHHx alone group did not. Electrophysiological evaluation showed better results in autograft and PHBHHx with hMSC groups when compared to PHBHHx alone group. There was no statistical difference between autograft and PHBHHx with hMSC groups. Histological evaluation showed regenerated axons in each group. Autograft group was better than the others, and PHBHHx with hMSC group was better than PHBHHx alone group both for axonal regeneration and myelin formation. This study showed that the nerve grafts which were prepared from PHBHHx with oriented nanofiber three-dimensional surfaces aided to nerve regeneration, either used alone or with hMSC. PHBHHx provided better nerve regeneration when used with hMSCs inside than alone, and reached the same statistical treatment effect in functional evaluation and electrophysiological evaluation when compared to autografting.
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Synthesis, characterization and application of methyl 3,5-disulfo-benzoate dipotassium dihydrate as nucleating agent for poly(L-lactide). Chem Res Chin Univ 2013. [DOI: 10.1007/s40242-013-3275-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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García-García JM, Bernal MM, Verdejo R, López-Manchado MA, Doncel-Pérez E, Garrido L, Quijada-Garrido I. Semiconductive bionanocomposites of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) and MWCNTs for neural growth applications. ACTA ACUST UNITED AC 2013. [DOI: 10.1002/polb.23417] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- José M. García-García
- Instituto de Ciencia y Tecnología de Polímeros; ICTP-CSIC, Juan de la Cierva 3 Madrid 28006 Spain
| | - M. Mar Bernal
- Instituto de Ciencia y Tecnología de Polímeros; ICTP-CSIC, Juan de la Cierva 3 Madrid 28006 Spain
| | - Raquel Verdejo
- Instituto de Ciencia y Tecnología de Polímeros; ICTP-CSIC, Juan de la Cierva 3 Madrid 28006 Spain
| | - Miguel A. López-Manchado
- Instituto de Ciencia y Tecnología de Polímeros; ICTP-CSIC, Juan de la Cierva 3 Madrid 28006 Spain
| | - Ernesto Doncel-Pérez
- Grupo de Química Neuro-Regenerativa Unidad Neurología Experimental; Hospital Nacional de Parapléjicos; 45071 Toledo Spain
| | - Leoncio Garrido
- Instituto de Ciencia y Tecnología de Polímeros; ICTP-CSIC, Juan de la Cierva 3 Madrid 28006 Spain
| | - Isabel Quijada-Garrido
- Instituto de Ciencia y Tecnología de Polímeros; ICTP-CSIC, Juan de la Cierva 3 Madrid 28006 Spain
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Bonartsev AP, Yakovlev SG, Zharkova II, Boskhomdzhiev AP, Bagrov DV, Myshkina VL, Makhina TK, Kharitonova EP, Samsonova OV, Feofanov AV, Voinova VV, Zernov AL, Efremov YM, Bonartseva GA, Shaitan KV, Kirpichnikov MP. Cell attachment on poly(3-hydroxybutyrate)-poly(ethylene glycol) copolymer produced by Azotobacter chroococcum 7B. BMC BIOCHEMISTRY 2013; 14:12. [PMID: 23692611 PMCID: PMC3724502 DOI: 10.1186/1471-2091-14-12] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2012] [Accepted: 04/19/2013] [Indexed: 11/18/2022]
Abstract
BACKGROUND The improvement of biomedical properties, e.g. biocompatibility, of poly(3-hydroxyalkanoates) (PHAs) by copolymerization is a promising trend in bioengineering. We used strain Azotobacter chroococcum 7B, an effective producer of PHAs, for biosynthesis of not only poly(3-hydroxybutyrate) (PHB) and its main copolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV), but also alternative copolymer, poly(3-hydroxybutyrate)-poly(ethylene glycol) (PHB-PEG). RESULTS In biosynthesis we used sucrose as the primary carbon source and valeric acid or poly(ethylene glycol) 300 (PEG 300) as additional carbon sources. The chemical structure of PHB-PEG and PHB-HV was confirmed by 1H nuclear-magnetic resonance (1H NMR) analysis. The physico-chemical properties (molecular weight, crystallinity, hydrophilicity, surface energy) and surface morphology of films from PHB copolymers were studied. To study copolymers biocompatibility in vitro the protein adsorption and COS-1 fibroblasts growth on biopolymer films by XTT assay were analyzed. Both copolymers had changed physico-chemical properties compared to PHB homopolymer: PHB-HV and PHB-PEG had less crystallinity than PHB; PHB-HV was more hydrophobic than PHB in contrast to PHB-PEG appeared to have greater hydrophilicity than PHB; whereas the morphology of polymer films did not differ significantly. The protein adsorption to PHB-PEG was greater and more uniform than to PHB and PHB-PEG copolymer promoted better growth of COS-1 fibroblasts compared with PHB homopolymer. CONCLUSIONS Thus, despite low EG-monomers content in bacterial origin PHB-PEG copolymer, this polymer demonstrated significant improvement in biocompatibility in contrast to PHB and PHB-HV copolymers, which may be coupled with increased protein adsorption and hydrophilicity of PEG-containing copolymer.
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Affiliation(s)
- Anton P Bonartsev
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
- A.N.Bach Institute of Biochemistry RAS, Leninskii av., 33-2, Moscow, 119071, Russia
| | - Sergey G Yakovlev
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
- A.N.Bach Institute of Biochemistry RAS, Leninskii av., 33-2, Moscow, 119071, Russia
| | - Irina I Zharkova
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
| | | | - Dmitrii V Bagrov
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
| | - Vera L Myshkina
- A.N.Bach Institute of Biochemistry RAS, Leninskii av., 33-2, Moscow, 119071, Russia
| | - Tatiana K Makhina
- A.N.Bach Institute of Biochemistry RAS, Leninskii av., 33-2, Moscow, 119071, Russia
| | - Elena P Kharitonova
- Faculty of Physics, M.V.Lomonosov Moscow State University, Leninskie gory, 1-2, Moscow, 119991, Russia
| | - Olga V Samsonova
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
| | - Alexey V Feofanov
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
| | - Vera V Voinova
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
- A.N.Bach Institute of Biochemistry RAS, Leninskii av., 33-2, Moscow, 119071, Russia
| | - Anton L Zernov
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
- A.N.Bach Institute of Biochemistry RAS, Leninskii av., 33-2, Moscow, 119071, Russia
| | - Yurii M Efremov
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
| | - Garina A Bonartseva
- A.N.Bach Institute of Biochemistry RAS, Leninskii av., 33-2, Moscow, 119071, Russia
| | - Konstantin V Shaitan
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
| | - Michail P Kirpichnikov
- Faculty of Biology, M.V.Lomonosov Moscow State University, Leninskie gory, 1-12, Moscow, 119236, Russia
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Bonartsev A, Yakovlev S, Boskhomdzhiev A, Zharkova I, Bagrov D, Myshkina V, Mahina T, Kharitonova E, Samsonova O, Zernov A, Zhuikov V, Efremov Y, Voinova V, Bonartseva G, Shaitan K. The terpolymer produced by Azotobacter chroococcum 7B: effect of surface properties on cell attachment. PLoS One 2013; 8:e57200. [PMID: 23468935 PMCID: PMC3582562 DOI: 10.1371/journal.pone.0057200] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Accepted: 01/18/2013] [Indexed: 12/02/2022] Open
Abstract
The copolymerization of poly(3-hydroxybutyrate) (PHB) is a promising trend in bioengineering to improve biomedical properties, e.g. biocompatibility, of this biodegradable polymer. We used strain Azotobacter chroococcum 7B, an effective producer of PHB, for biosynthesis of not only homopolymer and its main copolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV), but also novel terpolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-poly(ethylene glycol) (PHB-HV-PEG), using sucrose as the primary carbon source and valeric acid and poly(ethylene glycol) 300 (PEG 300) as additional carbon sources. The chemical structure of PHB-HV-PEG was confirmed by (1)H nuclear-magnetic resonance analysis. The physico-chemical properties (molecular weight, crystallinity, hydrophilicity, surface energy) of produced biopolymer, the protein adsorption to the terpolymer, and cell growth on biopolymer films were studied. Despite of low EG-monomers content in bacterial-origin PHB-HV-PEG polymer, the terpolymer demonstrated significant improvement in biocompatibility in vitro in contrast to PHB and PHB-HV polymers, which may be coupled with increased protein adsorption, hydrophilicity and surface roughness of PEG-containing copolymer.
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Affiliation(s)
- Anton Bonartsev
- Faculty of Biology, Moscow State University, Moscow, Russia.
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Lu X, Wang L, Yang Z, Lu H. Strategies of polyhydroxyalkanoates modification for the medical application in neural regeneration/nerve tissue engineering. ACTA ACUST UNITED AC 2013. [DOI: 10.4236/abb.2013.46097] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Wang H, Feng Y, Fang Z, Yuan W, Khan M. Co-electrospun blends of PU and PEG as potential biocompatible scaffolds for small-diameter vascular tissue engineering. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2012. [DOI: 10.1016/j.msec.2012.07.001] [Citation(s) in RCA: 104] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Lomas AJ, Chen GG, El Haj AJ, Forsyth NR. Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) supports adhesion and migration of mesenchymal stem cells and tenocytes. World J Stem Cells 2012; 4. [PMID: 23193433 PMCID: PMC3507844 DOI: 10.4252/wjsc.v4.i9.94] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To establish the potential of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) as a material for tendon repair. METHODS The biocompatibility of PHBHHx with both rat tenocytes (rT) and human mesenchymal stem cells (hMSC) was explored by monitoring adhesive characteristics on films of varying weight/volume ratios coupled to a culture atmosphere of either 21% O(2) (air) or 2% O(2) (physiological normoxia). The diameter and stiffness of PHBHHx films was established using optical coherence tomography and mechanical testing, respectively. RESULTS Film thickness correlated directly with weight/volume PHBHHx (r(2) = 0.9473) ranging from 0.1 mm (0.8% weight/volume) to 0.19 mm (2.4% weight/volume). Film stiffness on the other hand displayed a biphasic response which increased rapidly at values > 1.6% weight/volume. Optimal cell attachment of rT required films of ≥ 1.6% and ≥ 2.0% weight/volume PHBHHx in 2% O(2) and 21% O(2) respectively. A qualitative adhesion increase was noted for hMSC in films ≥ 1.2% weight/volume, becoming significant at 2% weight/volume in 2% O(2). An increase in cell adhesion was also noted with ≥ 2% weight/volume PHBHHx in 21% O(2). Cell migration into films was not observed. CONCLUSION This evaluation demonstrates that PHBHHx is a suitable polymer for future cell/polymer replacement strategies in tendon repair.
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Affiliation(s)
- Alex J Lomas
- Alex J Lomas, Alicia J El Haj, Nicholas R Forsyth, Guy Hilton Research Centre, Keele University, Stoke on Trent, ST4 7QB, United Kingdom
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Hazer DB, Kılıçay E, Hazer B. Poly(3-hydroxyalkanoate)s: Diversification and biomedical applications. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2012. [DOI: 10.1016/j.msec.2012.01.021] [Citation(s) in RCA: 122] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Artsis MI, Bonartsev AP, Iordanskii AL, Bonartseva GA, Zaikov GE. Biodegradation and Medical Application of Microbial Poly(3-Hydroxybutyrate). MOLECULAR CRYSTALS AND LIQUID CRYSTALS 2012; 555:232-262. [DOI: 10.1080/15421406.2012.635549] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
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Qu XH, Wu Q, Chen GQ. In vitro study on hemocompatibility and cytocompatibility of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2012. [DOI: 10.1163/156856206778530704] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Chen Z, Cheng S, Li Z, Xu K, Chen GQ. Synthesis, Characterization and Cell Compatibility of Novel Poly(ester urethane)s Based on Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) and Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) Prepared by Melting Polymerization. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2012; 20:1451-71. [DOI: 10.1163/092050609x12457419007621] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Zhifei Chen
- a Multidisciplinary Research Center, Shantou University, Shantou, Guangdong 515063, P. R. China
| | - Shaoting Cheng
- b Multidisciplinary Research Center, Shantou University, Shantou, Guangdong 515063, P. R. China
| | - Zibiao Li
- c Multidisciplinary Research Center, Shantou University, Shantou, Guangdong 515063, P. R. China
| | - Kaitian Xu
- d Multidisciplinary Research Center, Shantou University, Shantou, Guangdong 515063, P. R. China
| | - Guo-Qiang Chen
- e Multidisciplinary Research Center, Shantou University, Shantou, Guangdong 515063, P. R. China
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Dong CL, Li SY, Wang Y, Dong Y, Tang JZ, Chen JC, Chen GQ. The cytocompatability of polyhydroxyalkanoates coated with a fusion protein of PHA repressor protein (PhaR) and Lys-Gln-Ala-Gly-Asp-Val (KQAGDV) polypeptide. Biomaterials 2012; 33:2593-9. [DOI: 10.1016/j.biomaterials.2011.12.020] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Accepted: 12/09/2011] [Indexed: 12/20/2022]
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Zhijiang C, Chengwei H, Guang Y. Poly(3-hydroxubutyrate-co-4-hydroxubutyrate)/bacterial cellulose composite porous scaffold: Preparation, characterization and biocompatibility evaluation. Carbohydr Polym 2012. [DOI: 10.1016/j.carbpol.2011.08.037] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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Yu BY, Chen PY, Sun YM, Lee YT, Young TH. Response of human mesenchymal stem cells (hMSCs) to the topographic variation of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) films. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2011; 23:1-26. [PMID: 21762548 DOI: 10.1163/092050610x541386] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The influence of the topographic morphology of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) films on human mesenchymal stem cells (hMSCs) was investigated in this study. PHBHHx films with various surface characteristics were prepared by compression-molding, solvent-casting and electrospinning. The adhesion, proliferation and differentiation behaviors of hMSCs were significantly modulated by the surface characteristics of these films. HMSCs could aggregate and form cellular clusters on the cast PHBHHx films, and the time to form cellular aggregates increased as the surface roughness increased. The aggregated hMSCs on the cast films kept their original surface markers and presented much higher viability during the regular culture and lower differentiation ability upon osteogenic induction than the spread cells on the compression-molded films and TCPS. HMSCs spread well and showed a specific orientation on the surface of the random electrospun fibrous films, they were not able to migrate into the interior of electrospun fibrous films, and they revealed the highest viability during the regular culture but a lower differentiation activity upon osteogenic induction. The electrospun fibrous PHBHHx films could serve as a suitable substrate for large quantity culturing of hMSCs when undifferentiated hMSCs are desired.
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Affiliation(s)
- Bo-Yi Yu
- Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li, Taoyuan, Taiwan 320, Republic of China
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Rai R, Yunos DM, Boccaccini AR, Knowles JC, Barker IA, Howdle SM, Tredwell GD, Keshavarz T, Roy I. Poly-3-hydroxyoctanoate P(3HO), a Medium Chain Length Polyhydroxyalkanoate Homopolymer from Pseudomonas mendocina. Biomacromolecules 2011; 12:2126-36. [DOI: 10.1021/bm2001999] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Ranjana Rai
- Department of Molecular and Applied Biosciences, School of Life Sciences, University of Westminster, London W1W 6UW, United Kingdom
| | - Darmawati M. Yunos
- Department of Materials, Imperial College London, London SW7 2AZ, United Kingdom
| | - Aldo R. Boccaccini
- Department of Materials, Imperial College London, London SW7 2AZ, United Kingdom
- Department of Materials Science and Engineering, University of Erlangen−Nuremberg, Cauestr. 6. 91058, Erlangen, Germany
| | - Jonathan C. Knowles
- Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, London WCIX 8LD, United Kingdom
- WCU Research Centre of Nanobiomedical Science, Dankook University, San#29, Anseo-dong, Dongnam-gu, Cheonan-si, Chungnam, 330-714, South Korea
| | - Ian A. Barker
- School of Chemistry, University of Nottingham, NG7 2RD, United Kingdom
| | - Steven M. Howdle
- School of Chemistry, University of Nottingham, NG7 2RD, United Kingdom
| | - Gregory D. Tredwell
- Department of Chemistry, Imperial College London, London SW7 2AZ, United Kingdom
| | - Tajalli Keshavarz
- Department of Molecular and Applied Biosciences, School of Life Sciences, University of Westminster, London W1W 6UW, United Kingdom
| | - Ipsita Roy
- Department of Molecular and Applied Biosciences, School of Life Sciences, University of Westminster, London W1W 6UW, United Kingdom
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Application of polyhydroxyalkanoate binding protein PhaP as a bio-surfactant. Appl Microbiol Biotechnol 2011; 91:1037-47. [PMID: 21590291 DOI: 10.1007/s00253-011-3258-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Revised: 03/16/2011] [Accepted: 04/17/2011] [Indexed: 01/19/2023]
Abstract
PhaP or phasin is an amphiphilic protein located on surfaces of microbial storage polyhydroxyalkanoates granules. This study aimed to explore amphiphilic properties of PhaP for possible application as a protein surfactant. Following agents were used to conduct this study as controls including bovine serum albumin, sodium dodecyl sulfate (SDS), Tween 20, sodium oleate, a commercial liquefied detergent together with the same amount of PhaP. Among all these tested control surfactants, PhaP showed the strongest effect to form emulsions with lubricating oil, diesel, and soybean oil, respectively. PhaP emulsion stability study compared with SDS revealed that PhaP had a stronger capability to maintain a very stable emulsion layer after 30 days while SDS lost half and two-thirds of its capacity after 2 and 30 days, respectively. When PhaP was more than 200 μg/ml in the water, all liquids started to exhibit stable emulsion layers. Similar to SDS, PhaP significantly reduced the water contact angles of water on a hydrophobic film of biaxially oriented polypropylene. PhaP was thermally very stable, it showed ability to form emulsion and to bind to the surface of polyhydroxybutyrate nanoparticles after a 60- min heating process at 95 °C. It is therefore concluded that PhaP is a protein with thermally stable property for application as natural and environmentally friendly surfactant for food, cosmetic, and pharmaceutical usages.
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Peng SW, Guo XY, Shang GG, Li J, Xu XY, You ML, Li P, Chen GQ. An assessment of the risks of carcinogenicity associated with polyhydroxyalkanoates through an analysis of DNA aneuploid and telomerase activity. Biomaterials 2011; 32:2546-55. [DOI: 10.1016/j.biomaterials.2010.12.051] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2010] [Accepted: 12/29/2010] [Indexed: 01/23/2023]
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Bonartsev AP, Bonartseva GA, Shaitan KV, Kirpichnikov MP. Poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate)-based biopolymer systems. BIOCHEMISTRY (MOSCOW) SUPPLEMENT SERIES B: BIOMEDICAL CHEMISTRY 2011; 5:10-21. [DOI: 10.1134/s1990750811010045] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
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Bonartzev A, Bonartzeva G, Shaitan K, Kirpichnikov M. Poly(3-hydroxybutyrate) and biopolymer systems on the basis of this polyester. ACTA ACUST UNITED AC 2011. [DOI: 10.18097/pbmc20115704374] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Biodegradable biopolymers attract much attention in biology and medicine due to its wide application. The present review is designed to be a comprehensive source for research of biodegradable and biocompatible bacterial polymer, poly(3-hydroxybutyrate). This paper focuses on basic properties of biopolymer: biodegradability and biocompatibility, as well as on biopolymer systems: various materials, devices and compositions on the basis of biopolymer. Application of biopolymer systems based on poly(3-hydroxybutyrate) in medicine as surgical implants, in bioengineering as scaffold for cell cultures, and in pharmacy as drug dosage forms and drug systems is observed in the present review.
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Affiliation(s)
- A.P. Bonartzev
- Lomonosov Moscow State University
Bakh Institute of Biochemistry RAS
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47
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You M, Peng G, Li J, Ma P, Wang Z, Shu W, Peng S, Chen GQ. Chondrogenic differentiation of human bone marrow mesenchymal stem cells on polyhydroxyalkanoate (PHA) scaffolds coated with PHA granule binding protein PhaP fused with RGD peptide. Biomaterials 2010; 32:2305-13. [PMID: 21190731 DOI: 10.1016/j.biomaterials.2010.12.009] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2010] [Accepted: 12/04/2010] [Indexed: 12/13/2022]
Abstract
Hydrophobic polyhydroxyalkanoate (PHA) scaffolds made of a copolyester of 3-hydroxybutyrate-co-hydroxyhexanoate (PHBHHx) were coated with a fusion protein PHA granule binding protein PhaP fused with RGD peptide (PhaP-RGD). Human bone marrow mesenchymal stem cells (hBMSCs) were inoculated on/in the scaffolds for formation of articular cartilages derived from chondrogenic differentiation of hBMSCs for cartilage tissue engineering. PhaP-RGD coating led to more homogeneous spread of cells, better cell adhesion, proliferation and chondrogenic differentiation in the scaffolds compared with those of PhaP coated or uncoated scaffolds immerging in serum minus chondrogenic induction medium. In addition, more extracellular matrices were produced by the differentiated cells over a period of 14 days on/in the PhaP-RGD coated scaffolds evidenced by scanning electron microscopy imaging, enhanced expression of chondrocyte specific genes including SOX-9, aggrecan and type II collagen, suggesting the positive effect of RGD on extracellular matrix production. Furthermore, cartilage-specific extracellular substances sulphated glycosaminoglycans (sGAG) and total collagen content found on/in the PhaP-RGD coated scaffolds were significantly more compared with that produced by the control and PhaP only coated scaffolds. Homogeneously distributed chondrocytes-like cells forming cartilage-like matrices were observed on/in the PhaP-RGD coated scaffolds after 3 weeks. The results suggested that PhaP-RGD coated PHBHHx scaffold promoted chondrogenic differentiation of hBMSCs and could support cartilage tissue engineering.
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Affiliation(s)
- Mingliang You
- Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China
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Microbial production of polyhydroxyalkanoate block copolymer by recombinant Pseudomonas putida. Appl Microbiol Biotechnol 2010; 90:659-69. [PMID: 21181145 DOI: 10.1007/s00253-010-3069-2] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2010] [Revised: 12/07/2010] [Accepted: 12/07/2010] [Indexed: 10/18/2022]
Abstract
Polyhydroxyalkanoate (PHA) synthesis genes phaPCJ(Ac) cloned from Aeromonas caviae were transformed into Pseudomonas putida KTOY06ΔC, a mutant of P. putida KT2442, resulting in the ability of the recombinant P. putida KTOY06ΔC (phaPCJ(A.c)) to produce a short-chain-length and medium-chain-length PHA block copolymer consisting of poly-3-hydroxybutyrate (PHB) as one block and random copolymer of 3-hydroxyvalerate (3HV) and 3-hydroxyheptanoate (3HHp) as another block. The novel block polymer was studied by differential scanning calorimetry (DSC), nuclear magnetic resonance, and rheology measurements. DSC studies showed the polymer to possess two glass transition temperatures (T(g)), one melting temperature (T(m)) and one cool crystallization temperature (T(c)). Rheology studies clearly indicated a polymer chain re-arrangement in the copolymer; these studies confirmed the polymer to be a block copolymer, with over 70 mol% homopolymer (PHB) of 3-hydroxybutyrate (3HB) as one block and around 30 mol% random copolymers of 3HV and 3HHp as the second block. The block copolymer was shown to have the highest tensile strength and Young's modulus compared with a random copolymer with similar ratio and a blend of homopolymers PHB and PHVHHp with similar ratio. Compared with other commercially available PHA including PHB, PHBV, PHBHHx, and P3HB4HB, the short-chain- and medium-chain-length block copolymer PHB-b-PHVHHp showed differences in terms of mechanical properties and should draw more attentions from the PHA research community.
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Biosynthesis of polyhydroxyalkanoate homopolymers by Pseudomonas putida. Appl Microbiol Biotechnol 2010; 89:1497-507. [DOI: 10.1007/s00253-010-2964-x] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2010] [Revised: 10/13/2010] [Accepted: 10/14/2010] [Indexed: 09/29/2022]
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The use of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds for tarsal repair in eyelid reconstruction in the rat. Biomaterials 2010; 31:7512-8. [DOI: 10.1016/j.biomaterials.2010.06.044] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2010] [Accepted: 06/28/2010] [Indexed: 11/18/2022]
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