Applied Microbiology and Biotechnology

, Volume 103, Issue 5, pp 2007–2032 | Cite as

Biomedical applications of microbially engineered polyhydroxyalkanoates: an insight into recent advances, bottlenecks, and solutions

  • Akhilesh Kumar SinghEmail author
  • Janmejai Kumar Srivastava
  • Anuj Kumar Chandel
  • Laxuman Sharma
  • Nirupama Mallick
  • Satarudra Prakash Singh


Biopolymeric polyhydroxyalkanoates (PHAs) are fabricated and accumulated by microbes under unbalanced growth conditions, primarily by diverse genera of bacteria. Over the last two decades, microbially engineered PHAs gained substantial interest worldwide owing to their promising wide-range uses in biomedical field as biopolymeric biomaterials. Because of non-hazardous disintegration products, preferred surface alterations, inherent biocompatibility, modifiable mechanical properties, cultivation support for cells, adhesion devoid of carcinogenic impacts, and controllable biodegradability, the PHAs like poly-3-hydroxybutyrate, 3-hydroxybutyrate and 3-hydroxyvalerate co-polymers, 3-hydroxybutyrate and 4-hydroxybutyrate co-polymers, etc., are available for various medical applications. These PHAs have been exploited to design in vivo implants like sutures as well as valves for direct tissue repairing as well as in regeneration devices like bone graft substitutes, nerve guides as well as cardiovascular patches, etc. Furthermore, they are also emerged as attractive candidates for developing effective/novel drug delivery systems because of their biocompatibility and biodegradability with the ability to deliver and release the drugs at a specific site in a controllable manner and, therefore widen the therapeutic window with reduced side effects. However, there still remain some bottlenecks related to PHA purity, mechanical properties, biodegradability, etc., that are need to be addressed so as to make PHAs a realistic biomaterial. In addition, innovative approaches like PHAs co-production with other value-added products, etc., must be developed currently for economical PHA production. This review provides an insight toward the recent advances, bottlenecks, and potential solutions for prospective biomedical applications of PHAs with conclusion that relatively little research/study has been performed presently toward the viability of PHAs as realistic biopolymeric biomaterials.


Biopolyesters PHAs Polyhydroxyalkanoates Biodegradability Biocompatibility Cytotoxicity Biomaterial Crystallinity Drug delivery systems Biomedical applications 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Abdelwahab MA, El-Barbary AA, El-Said KS, El Naggar SA, ElKholy HM (2019) Evaluation of antibacterial and anticancer properties of poly(3-hydroxybutyrate) functionalized with different amino compounds. Int J Biol Macromol 122:793–805PubMedCrossRefGoogle Scholar
  2. Ali I, Jamil N (2016) Polyhydroxyalkanoates: current applications in the medical field. Front Biol 11:19–27CrossRefGoogle Scholar
  3. Alves LP, Teixeira CS, Tirapelle EF, Donatti L, Tadra-Sfeir MZ, Steffens MB, de Souza EM, de Oliveira PF, Chubatsu LS, Müller-Santos M (2016) Backup expression of the PhaP2 Phasin compensates for phaP1 deletion in Herbaspirillum seropedicae, maintaining fitness and PHB accumulation. Front Microbiol 7:739PubMedPubMedCentralGoogle Scholar
  4. Anjum A, Zuber M, Zia KM, Noreen A, Anjum MN, Tabasum S (2016) Microbial production of polyhydroxyalkanoates (PHAs) and its copolymers: a review of recent advancements. Int J Biol Macromol 89:161–174PubMedCrossRefGoogle Scholar
  5. Ansari NF, Annuar MSM (2018) Functionalization of medium-chain-length poly (3-hydroxyalkanoates) as amphiphilic material by graft copolymerization with glycerol 1, 3-diglycerolate diacrylate and its mechanism. J Macromol Sci A 55:66–74CrossRefGoogle Scholar
  6. Basnett P, Ching KY, Stolz M, Knowles JC, Boccaccini AR, Smith C, Locke IC, Keshavarz T, Roy I (2013) Novel poly (3-hydroxyoctanoate)/poly (3-hydroxybutyrate) blends for medical applications. React Funct Polym 73:1340–1348CrossRefGoogle Scholar
  7. Benavente J, Vazquez MI (2004) Effect of age and chemical treatments on characteristic parameters for active and porous sublayers of polymeric composite membranes. J Colloid Interface Sci 273:547–555PubMedCrossRefGoogle Scholar
  8. Bhatia SK, Wadhwa P, Hong JW, Hong YG, Jeon JM, Lee ES, Yang YH (2019) Lipase mediated functionalization of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) with ascorbic acid into an antioxidant active biomaterial. Int J Biol Macromol 123:117–123PubMedCrossRefGoogle Scholar
  9. Bhattacharya S, Dubey S, Singh P, Shrivastava A, Mishra S (2016) Biodegradable polymeric substances produced by a marine bacterium from a surplus stream of the biodiesel industry. Bioengineering 3:34–44PubMedCentralCrossRefGoogle Scholar
  10. Bissery MC, Valeriote F, Thies C (1985) Therapeutic efficacy of CCNU-loaded microspheres prepared from poly(D,L)lactide (PLA) or poly-b-hydroxybutyrate (PHB) against Lewis lung (LL) carcinoma. Proc Am Assoc Cancer Res 26:355–355Google Scholar
  11. Bonthrone KM, Clauss J, Horowitz DM, Hunter BK, Sanders JKM (1992) The biological and physical chemistry of polyhydroxyalkanoates as seen by NMR spectroscopy. FEMS Microbiol Rev 10:269–278CrossRefGoogle Scholar
  12. Bowald SF, Johansson EG (1990) A novel surgical material. European Patent No. 0349505A2Google Scholar
  13. Brandl H, Gross RA, Lenz RW, Fuller RC (1990) Plastics from bacteria and for bacteria: poly(β-hydroxyalkanoates) as natural, biocompatible, and biodegradable polyesters. Adv Biochem Eng Biotechnol 41:77–93PubMedGoogle Scholar
  14. Brigham CJ, Sinskey AJ (2012) Applications of polyhydroxyalkanoates in the medical industry. Int J Biotechnol Wellness Ind 1:53–60Google Scholar
  15. Brzeska J, Heimowska A, Janeczek H, Kowalczuk M, Rutkowska M (2014) Polyurethanes based on atactic poly[(R,S)-3-hydroxybutyrate]: preliminary degradation studies in simulated body fluids. J Polym Environ 22:176–182CrossRefGoogle Scholar
  16. Bugnicourt E, Cinelli P, Lazzeri A, Alvarez V (2014) Polyhydroxyalkanoate (PHA): review of synthesis, characteristics, processing and potential applications in packaging. Express Polym Lett 8:791–808CrossRefGoogle Scholar
  17. Byrom D (1987) Polymer synthesis by microorganisms: technology and economics. Trends Biotechnol 5:246–250CrossRefGoogle Scholar
  18. Cao Q, Zhang J, Liu H, Wu Q, Chen J, Chen GQ (2014) The mechanism of anti-osteoporosis effects of 3-hydroxybutyrate and derivatives under simulated microgravity. Biomaterials 35:8273–8283PubMedCrossRefGoogle Scholar
  19. Caon T, Berezina N, Lin CSK, Fakhouri FM, Martelli SM (2014) Polyhydroxyalkanoates and their potential in controlled-release drug delivery systems: biomedical applications and factors affecting the drug release. In: Linping W (ed) Polyhydroxyalkanoates (PHAs): biosynthesis, industrial production and applications in medicine. Nova Science Publishers, Inc., Hauppauge, p 219–236Google Scholar
  20. Capulli AK, Emmert MY, Pasqualini FS, Kehl D, Caliskan E, Lind JU, Sheehy SP, Park SJ, Ahn S, Weber B, Goss JA, Hoerstrup SP, Parker KK (2017) JetValve: rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement. Biomaterials 133:229–241Google Scholar
  21. Carr NG (1966) The occurrence of poly-β-hydroxybutyrate in the blue-green alga, Chlorogloea fritschii. Biochem Biophys Acta 120:308–310PubMedGoogle Scholar
  22. Castilho LR, Mitchell DA, Freire DMG (2009) Production of polyhydroxyalkanoates (PHAs) from waste materials and by-products by submerged and solid-state fermentation. Bioresour Technol 100:5996–6009PubMedCrossRefGoogle Scholar
  23. Chandel AK, Garlapati VK, Singh AK, Antunes FAF, da Silva SS (2018) The path forward for lignocellulose biorefineries: bottlenecks, solutions, and perspective on commercialization. Bioresour Technol 264:370–381PubMedCrossRefGoogle Scholar
  24. Chaput C, Yahia LH, Selmani A, Rivard C-H (1995) Natural poly(hydroxybutyrate-hydroxyvalerate) polymers as degradable biomaterials. Mat Res Soc Symp Proc 385:49–54CrossRefGoogle Scholar
  25. Chen W, Tong YW (2012) PHBV microspheres as neural tissue engineering scaffold support neuronal cell growth and axon–dendrite polarization. Acta Biomater 8:540–548PubMedCrossRefGoogle Scholar
  26. Chen G-Q, Wu Q (2005) The application of polyhydroxyalkanoates as tissue engineering materials. Biomaterials 26:6565–6578PubMedCrossRefGoogle Scholar
  27. Chen G-Q, Zhang J (2017) Microbial polyhydroxyalkanoates as medical implant biomaterials. Artif Cells Nanomed Biotechnol 46:1–18PubMedCrossRefGoogle Scholar
  28. Chen Y, Tsai Y, Chou IN, Tseng SH, Wu HS (2014) Application of biodegradable polyhydroxyalkanoates as surgical films for ventral hernia repair in mice. Int J Polym Sci 2014:789681Google Scholar
  29. Choi J, Lee SY (1999) Factors affecting the economics of polyhydroxyalkanoate production by bacterial fermentation. Appl Microbiol Biotechnol 51:13–21CrossRefGoogle Scholar
  30. Chuah JA, Yamada M, Taguchi S, Sudesh K, Doi Y, Numata K (2013) Biosynthesis and characterization of polyhydroxyalkanoate containing 5-hydroxyvalerate units: effects of 5HV units on biodegradability, cytotoxicity, mechanical and thermal properties. Polym Degrad Stab 98:331–338CrossRefGoogle Scholar
  31. Chung CW, Kim HW, Kim YB, Rhee YH (2003) Poly(ethylene glycol)-grafted poly(3-hydroxyundecenoate) networks for enhanced blood compatibility. Int J Biol Macromol 32:17–22PubMedCrossRefGoogle Scholar
  32. Czech Republic (2015) Accessed 14 Dec 2018
  33. Del Gaudio C, Fioravanzo L, Folin M, Marchi F, Ercolani E, Bianco A (2012) Electrospun tubular scaffolds: on the effectiveness of blending poly(e-caprolactone) with poly(3-hydroxybutyrate-co-3-hydroxyvalerate). J Biomed Mater Res B Appl Biomater 100:1883–1898PubMedCrossRefGoogle Scholar
  34. Devi ES, Vijayendra SVN, Shamala TR (2012) Exploration of rice bran, an agro-industry residue, for the production of intra-and extra-cellular polymers by Sinorhizobium meliloti MTCC 100. Biocatal Agric Biotechnol 1:80–84CrossRefGoogle Scholar
  35. DiGregorio BE (2009) Biobased performance bioplastic: Mirel. Chem Biol 16:1–2PubMedCrossRefGoogle Scholar
  36. Dinjaski N, Fernández-Gutiérrez M, Selvam S, Parra-Ruiz FJ, Lehman SM, San Román J, García E, García JL, García AJ, Prieto MA (2014) PHACOS, a functionalized bacterial polyester with bactericidal activity against methicillin-resistant Staphylococcus aureus. Biomaterials 35:14–24PubMedCrossRefGoogle Scholar
  37. Dumaz N, Drougard C, Sarasin A, Daya-Grosjean L (1993) Specific UV-induced mutation spectrum in the p53 gene of skin tumors from DNA-repair-deficient xeroderma pigmentosum patients. Proc Natl Acad Sci U S A 90:10529–10533PubMedPubMedCentralCrossRefGoogle Scholar
  38. Durai P, Batool M, Choi S (2015) Structure and effects of cyanobacterial lipopolysaccharides. Mar Drugs 13:4217–4230PubMedPubMedCentralCrossRefGoogle Scholar
  39. Emmert MY, Weber B, Behr L, Sammut S, Frauenfelder T, Wolint P, Scherman J, Bettex D, Grünenfelder J, Falk V, Hoerstrup SP (2014) Transcatheter aortic valve implantation using anatomically oriented, marrow stromal cell-based, stented, tissue-engineered heart valves: technical considerations and implications for translational cell-based heart valve concepts. Eur J Cardiothorac Surg 45:61–68PubMedCrossRefGoogle Scholar
  40. Fava F, Totaro G, Gavrilescu M (2015) Material & energy recovery and sustainable development, ECOMONDO 2014. Environ Eng Manag J 14:1475–1471Google Scholar
  41. Fu X-Z, Tan D, Aibaidula G, Wu Q, Chen J-C, Chen G-Q (2014) Development of Halomonas TD01 as a host for open production of chemicals. Metab Eng 23:78–91PubMedCrossRefGoogle Scholar
  42. Furrer P, Panke S, Zinn M (2007) Efficient recovery of low endotoxin medium-chain-length poly([R]-3-hydroxyalkanoate) from bacterial biomass. J Microbiol Methods 69:206–213PubMedCrossRefGoogle Scholar
  43. Furrer P, Zinn M, Panke S (2008) Polyhydroxyalkanoate and its potential for biomedical applications. In: Reis RL, Neves NM, Mano JF, Gomes ME, Marques AP, Azevedo HS (eds) Natural-based polymers for biomedical applications. Elsevier, Amsterdam, pp 416–445Google Scholar
  44. Gardel M, Schwarz U (2010) Cell–substrate interactions. J Phys Condens Matter 22:190301PubMedCrossRefGoogle Scholar
  45. Geiger B, Spatz JP, Bershadsky AD (2009) Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol 10:21–33PubMedCrossRefGoogle Scholar
  46. Gould PL, Holland SJ, Tighe BJ (1987) Polymers for biodegradable medical devices. IV. Hydroxybutyrate-valerate copolymers as non-disintegrating matrices for controlled release oral dosage forms. Int J Pharm 38:231–237CrossRefGoogle Scholar
  47. Gu P, Kang J, Yang F, Wang Q, Liang Q, Qi Q (2013) The improved L-tryptophan production in recombinant Escherichia coli by expressing the polyhydroxybutyrate synthesis pathway. Appl Microbiol Biotechnol 97:4121–4127PubMedCrossRefGoogle Scholar
  48. Gursel I, Korkusuz F, Turesin F, Gurdal Alaeddinoglu N, Hasirci V (2001) In vivo application of biodegradable controlled antibiotic release systems for the treatment of implant-related osteomyelitis. Biomaterials 22:73–80PubMedCrossRefGoogle Scholar
  49. Hazari A, Johansson-Ruden G, Bostrom KJ, Ljungberg C, Terenghi G, Green C, Wiberg M (1999a) A new resorbable wrap around implant as an alternative nerve repair technique. J Hand Surg Br 24B:291–295CrossRefGoogle Scholar
  50. Hazari A, Wiberg M, Johansson-Ruden G, Green C, Terenghi G (1999b) A resorbable nerve conduit as an alternative to nerve autograft in nerve gap repair. Br J Plast Surg 52:653–657PubMedCrossRefGoogle Scholar
  51. Hazer B, Steinbüchel A (2007) Increased diversification of polyhydroxyalkanoates by modification reactions for industrial and medical applications. Appl Microbiol Biotechnol 74:1–12PubMedCrossRefGoogle Scholar
  52. Hazer DB, Kiliçay E, Hazer B (2012) Poly(3-hydroxyalkanoate)s: diversification and biomedical applications: a state of the art review. Mater Sci Eng C 32:637–647CrossRefGoogle Scholar
  53. He Y, Hu Z, Ren M, Ding C, Chen P, Gu Q, Wu Q (2014) Evaluation of PHBHHx and PHBV/PLA fibers used as medical sutures. J Mater Sci Mater Med 25:561–571PubMedCrossRefGoogle Scholar
  54. Hollstein M, Sidransky D, Vogelstein B, Harris C (1991) p53 mutations in human cancers. Science 253:49–53PubMedCrossRefGoogle Scholar
  55. Hu YJ, Wei X, Zhao W, Liu YS, Chen GQ (2009) Biocompatibility of poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) with bone marrow mesenchymal stem cells. Acta Biomater 5:1115–1125PubMedCrossRefGoogle Scholar
  56. Inan K, Sal FA, Rahman A, Putman RJ, Agblevor FA, Miller CD (2016) Microbubble assisted polyhydroxybutyrate production in Escherichia coli. BMC Res Notes 9:338PubMedPubMedCentralCrossRefGoogle Scholar
  57. Insomphun C, Chuah JA, Kobayashi S, Fujiki T, Numata K (2017) Influence of hydroxyl groups on the cell viability of polyhydroxyalkanoate (PHA) scaffolds for tissue engineering. ACS Biomater Sci Eng 3:3064–3075CrossRefGoogle Scholar
  58. Janousek P, Kabelka Z, Rygl M, Lesný P, Grabec P, Fajstavr J, Jurovcík M, Snajdauf J (2006) Corrosive injury of the oesophagus in children. Int J Pediatr Otorhinolaryngol 70:1103–1107PubMedCrossRefGoogle Scholar
  59. Jendrossek D, Pfeiffer D (2014) New insights in the formation of polyhydroxyalkanoate granules (carbonosomes) and novel functions of poly(3-hydroxybutyrate). Environ Microbiol 16:2357–2373PubMedCrossRefGoogle Scholar
  60. Ji Y, Li XT, Chen GQ (2008) Interactions between a poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) terpolyester and human keratinocytes. Biomaterials 29:3807–3814PubMedCrossRefGoogle Scholar
  61. Jiang X, Ramsay JA, Ramsay BA (2006) Acetone extraction of mcl-PHA from Pseudomonas putida KT2440. J Microbiol Methods 67:212–219PubMedCrossRefGoogle Scholar
  62. Kai D, Loh XJ (2014) Polyhydroxyalkanoates: chemical modifications toward biomedical applications. ACS Sustain Chem Eng 2:106–119CrossRefGoogle Scholar
  63. Kang Z, Du L, Kang J, Wang Y, Wang Q, Liang Q, Qi Q (2011) Production of succinate and polyhydroxyalkanoate from substrate mixture by metabolically engineered Escherichia coli. Bioresour Technol 102:6600–6604Google Scholar
  64. Koller M, Maršálek L (2015) Cyanobacterial polyhydroxyalkanoate production: status quo and quo Vadis? Curr Biotechnol 4:464–480Google Scholar
  65. Kumar A, Srivastava JK, Mallick N, Singh AK (2015) Commercialization of bacterial cell factories for the sustainable production of polyhydroxyalkanoate thermoplastics: progress and prospects. Recent Pat Biotechnol 9:4–21PubMedCrossRefGoogle Scholar
  66. Kuroda K, Caputo GA (2013) Antimicrobial polymers as synthetic mimics of host-defense peptides. Interdiscip Rev Nanomed Nanobiotechnol 5:49–66CrossRefGoogle Scholar
  67. Leal-Egaña, Díaz-Cuenca A, Boccaccini AR (2013) Tuning of cell-biomaterial anchorage for tissue regeneration. Adv Mater 25:4049–4057PubMedCrossRefGoogle Scholar
  68. Lee SY, Choi JI, Han K, Song JY (1999) Removal of endotoxin during purification of poly(3–hydroxybutyrate) from gram-negative bacteria. Appl Environ Microbiol 65:2762–2764PubMedPubMedCentralGoogle Scholar
  69. Lee J, Jung SG, Park CS, Kim HY, Batt CA, Kim YR (2011) Tumor-specific hybrid polyhydroxybutyrate nanoparticle: surface modification of nanoparticle by enzymatically synthesized functional block copolymer. Bioorg Med Chem Lett 21:2941–2944Google Scholar
  70. Lenz RW, Marchessault RH (2005) Bacterial polyesters: biosynthesis, biodegradable plastics and biotechnology. Biomacromolecules 6:1–8PubMedCrossRefGoogle Scholar
  71. Levine AC, Sparano A, Twigg FF, Numata K, Nomura CT (2015) Influence of cross-linking on the physical properties and cytotoxicity of polyhydroxyalkanoate (PHA) scaffolds for tissue engineering. ACS Biomater Sci Eng 1:567–576CrossRefGoogle Scholar
  72. Li Z, Loh XJ (2015) Water soluble polyhydroxyalkanoates: future materials for therapeutic applications. Chem Soc Rev 44:2865–2879PubMedCrossRefGoogle Scholar
  73. Li J, Yun H, Gong Y, Zhao N, Zhang X (2005) Effects of surface modification of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) on physicochemical properties and on interactions with MC3T3-E1 cells. J Biomed Mater Res A 75:985–998PubMedCrossRefGoogle Scholar
  74. Li X, Chang H, Luo H, Wang Z, Zheng G, Lu X, He X, Chen F, Wang T, Liang J, Xu M (2015) Poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds coated with PhaP-RGD fusion protein promotes the proliferation and chondrogenic differentiation of human umbilical cord mesenchymal stem cells in vitro. J Biomed Mater Res A 103:1169–1175PubMedCrossRefGoogle Scholar
  75. Li X, Li X, Chen D, Guo J-L, Feng D-F, Sun M-Z, Lu Y, Chen D-Y, Zhao X, Feng X-Z (2016a) Evaluating the biological impact of polyhydroxyalkanoates (PHAs) on developmental and exploratory profile of zebrafish larvae. RSC Adv 6:37018–37030CrossRefGoogle Scholar
  76. Li Z, Yang J, Loh XJ (2016b) Polyhydroxyalkanoates: opening doors for a sustainable future. NPG Asia Mater 8:e265CrossRefGoogle Scholar
  77. Li T, Guo YY, Qiao GQ, Chen GQ (2016c) Microbial synthesis of 5-aminolevulinic acid and its coproduction with polyhydroxybutyrate. ACS Synth Biol 5:1264–1274PubMedCrossRefGoogle Scholar
  78. Li T, Ye J, Shen R, Zong Y, Zhao X, Lou C, Chen G-Q (2016d) Semirational approach for ultrahigh poly(3-hydroxybutyrate) accumulation in Escherichia coli by combining one-step library construction and high-throughput screening. ACS Synth Biol 5:1308–1317PubMedCrossRefGoogle Scholar
  79. Li T, Elhadi D, Chen GQ (2017) Co-production of microbial polyhydroxyalkanoates with other chemicals. Metab Eng 43:29–36PubMedCrossRefGoogle Scholar
  80. Liang Q, Qi Q (2014) From a co-production design to an integrated single-cell biorefinery. Biotechnol Adv 32:1328–1335PubMedCrossRefGoogle Scholar
  81. Licciardello G, Ferraro R, Russo M, Strozzi F, Catara AF, Bella P, Catara V (2016) Transcriptome analysis of Pseudomonas mediterranea and P. corrugata plant pathogens during accumulation of medium-chain-length PHAs by glycerol bioconversion. New Biotechnol 37:39–47CrossRefGoogle Scholar
  82. Liu S, Zhang G, Li X, Zhang J (2014) Microbial production and applications of 5-aminolevulinic acid. Appl Microbiol Biotechnol 98:7349–7357PubMedCrossRefGoogle Scholar
  83. Lizarraga-Valderrama LR, Nigmatullin R, Taylor C, Haycock JW, Claeyssens F, Knowles JC, Roy I (2015) Nerve tissue engineering using blends of poly (3-hydroxyalkanoates) for peripheral nerve regeneration. Eng Life Sci 15:612–621CrossRefGoogle Scholar
  84. Ljungberg C, Johansson RG, Bostrom KJ, Novikov L, Weiberg M (1999) Neuronal survival using a resorbable synthetic conduit as an alternative to primary nerve repair. Microsurgery 19:250–264CrossRefGoogle Scholar
  85. Löbler M, Saß M, Schmitz KP, Hopt UT (2002) Biomaterial implants induce the inflammation marker CRP at the site of implantation. J Biomed Mater Res 61:165–167PubMedCrossRefGoogle Scholar
  86. Loh XJ, Wang X, Li H, Li X, Li J (2007) Compositional study and cytotoxicity of biodegradable poly(ester urethane)s consisting of poly[(R)-3-Hydroxybutyrate] and poly(ethylene glycol). Mater Sci Eng C 27:267–273CrossRefGoogle Scholar
  87. Lomas AJ, Webb WR, Han J, Chen GQ, Sun X, Zhang Z, El Haj AJ, Forsyth NR (2013) Poly (3-hydroxybutyrate-co-3-hydroxyhexanoate)/collagen hybrid scaffolds for tissue engineering applications. Tissue Eng Part C Methods 19:577–585PubMedPubMedCentralCrossRefGoogle Scholar
  88. Lu X-Y, Ciraolo E, Stefenia R, Chen G-Q, Zhang Y, Hirsch E (2011) Sustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines. Appl Microbiol Biotechnol 89:1423–1433PubMedCrossRefGoogle Scholar
  89. Lu X, Wang L, Yang Z, Lu H (2013) Strategies of polyhydroxyalkanoates modification for the medical application in neural regeneration/nerve tissue engineering. Adv Biosci Biotechnol 4:731–740CrossRefGoogle Scholar
  90. Lu HX, Yang ZQ, Jiao Q, Wang YY, Wang L, Yang PB, Chen XL, Zhang PB, Wang P, Chen MX, Lu XY, Liu Y (2014) Low concentration of serum helps to maintain the characteristics of NSCs/NPCs on alkali-treated PHBHHx film in vitro. Neurol Res 36:207–214PubMedCrossRefGoogle Scholar
  91. M & M (2018) Markets and Markets Polyhydroxyalkanoate (PHA) Market by Type (Monomers, Co-Polymers, Terpolymers), Manufacturing Technology (Bacterial Fermentation, Biosynthesis, Enzymatic Catalysis), Application (Packaging, Bio Medical, Food Services, Agriculture)—Global Forecast to 2021 (Available online: (accessed on 10 December, 2018)
  92. Ma Z, Gao C, Gong Y, Shen J (2003) Chondrocyte behaviors on poly-L-lactic acid (PLLA) membranes containing hydroxyl, amide or carboxyl groups. Biomaterials 24:3725–3730PubMedCrossRefGoogle Scholar
  93. Mallick N, Sharma L, Singh AK (2007) Poly-β-hydroxybutyrate accumulation in Nostoc muscorum: effects of metabolic inhibitors. J Plant Physiol 164:312–317PubMedCrossRefGoogle Scholar
  94. Martínez V, García P, García JL, Prieto MA (2011) Controlled autolysis facilitates the polyhydroxyalkanoate recovery in Pseudomonas putida KT2440. Microb Biotechnol 4:533–547PubMedPubMedCentralCrossRefGoogle Scholar
  95. Masood F, Chen P, Yasin T, Fatima N, Hasan F, Hameed A (2013) Encapsulation of ellipticine in poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) based nanoparticles and its in vitro application. Mater Sci Eng C Mater 33:1054–1060CrossRefGoogle Scholar
  96. Masood F, Yasin T, Hameed A (2015) Polyhydroxyalkanoates—what are the uses? Current challenges and perspectives. Crit Rev Biotechnol 35:514–521PubMedCrossRefGoogle Scholar
  97. Mergaert J, Anderson C, Wouters A, Swings J, Kersters K (1992) Biodegradation of polyhydroxyalkanoates. FEMS Microbiol Rev 10:317–322CrossRefGoogle Scholar
  98. Montazeri M, Karbasi S, Foroughi M, Monshi A, Ebrahimi-Kahrizsangi R (2015) Evaluation of mechanical property and bioactivity of nano-bioglass 45S5 scaffold coated with poly-3-hydroxybutyrate. J Mater Sci Mater Med 26:62PubMedCrossRefGoogle Scholar
  99. Nair LS, Laurencin CT (2006) Polymers as biomaterials for tissue engineering and controlled drug delivery. Adv Biochem Eng Biotechnol 102:47–90PubMedGoogle Scholar
  100. Nigmatullin R, Thomas P, Lukasiewicz B, Puthussery H, Roy I (2015) Polyhydroxyalkanoates, a family of natural polymers, and their applications in drug delivery. J Chem Technol Biotechnol 90:1209–1221CrossRefGoogle Scholar
  101. Noble JR, Zhong ZH, Neumann AA, Melki JR, Clark SJ, Reddel RR (2004) Alterations in the p16INK4a and p53 tumor suppressor genes of hTERT-immortalized human fibroblasts. Oncogene 23:3116–3121PubMedCrossRefGoogle Scholar
  102. Obruca S, Sedlacek P, Koller M, Kucera D, Pernicova I (2018) Involvement of polyhydroxyalkanoates in stress resistance of microbial cells: biotechnological consequences and applications. Biotechnol Adv 36:856–870PubMedCrossRefGoogle Scholar
  103. Opitz F, Schenke-Layland K, Richter W, Martin DP, Degenkolbe I, Wahlers T, Stock UA (2004) Tissue engineering of ovine aortic blood vessel substitutes using applied shear stress and enzymatically derived vascular smooth muscle cells. Ann Biomed Eng 32:212–222PubMedCrossRefGoogle Scholar
  104. Pelham RJ Jr, Wang Y (1997) Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci USA 94:13661–13665Google Scholar
  105. Peng SW, Guo XY, Shang GG, Li J, Xu XY, You ML, Li P, Chen GQ (2011) An assessment of the risks of carcinogenicity associated with polyhydroxyalkanoates through an analysis of DNA aneuploid and telomerase activity. Biomaterials 32:2546–2555PubMedCrossRefGoogle Scholar
  106. Peptu C, Kowalczuk M (2018) Biomass-derived polyhydroxyalkanoates: biomedical applications. In: Popa V, Volf I (eds) Biomass as renewable raw material to obtain bioproducts of high-tech value. Elsevier, Peptu, p 271–313Google Scholar
  107. Plastics Technology (2017) (accessed on 10 December, 2018)
  108. Pramanik N, Bhattacharya S, Rath T, De J, Adhikary A, Basu RK, Kundu PP (2019) Polyhydroxybutyrate-co-hydroxyvalerate copolymer modified graphite oxide based 3D scaffold for tissue engineering application. Mater Sci Eng C 94:534–546CrossRefGoogle Scholar
  109. Pramual S, Assavanig A, Bergkvist M, Batt CA, Sunintaboon P, Lirdprapamongkol K, Svasti J, Niamsiri N (2016) Development and characterization of bio-derived polyhydroxyalkanoate nanoparticles as a delivery system for hydrophobic photodynamic therapy agents. J Mater Sci Mater Med 27:40PubMedCrossRefGoogle Scholar
  110. Qu XH, Wu Q, Liang J, Qu X, Wang SG, Chen GQ (2005) Enhanced vascular-related cellular affinity on surface modified copolyesters of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx). Biomaterials 26:6991–7001PubMedCrossRefGoogle Scholar
  111. Qu XH, Wu Q, Zhang KY, Chen GQ (2006) In vivo studies of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) based polymers: biodegradation and tissue reactions. Biomaterials 27:3540–3548PubMedGoogle Scholar
  112. Rai R, Yunos DM, Boccaccini AR, Knowles JC, Barker IA, Howdle SM, Tredwell GD, Keshavarz T, Roy I (2011) Poly-3hydroxyoctanoate P(3HO): a medium chain length polyhydroxyalkanoate homopolymer from Pseudomonas mendocina. Biomacromolecules 12:2126–2136PubMedCrossRefGoogle Scholar
  113. Rajaratanam DD, Ariffin H, Hassan MA, Nik Abd Rahman NMA, Nishida H (2018) 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 13:e0199742Google Scholar
  114. Rashid NFM, Azemi MAFM, Amiru AAA, Wahid MEA, Bhubalan K (2015) Simultaneous production of biopolymer and biosurfactant by genetically modified Pseudomonas aeruginosa UMTKB-5. Conference: international proceedings of chemical, biological and environmental engineering, Auckland, New Zealand, 90:3−8Google Scholar
  115. Rathbone S, Furrer P, Lübben J, Zinn M, Cartmell SJ (2010) Biocompatibility of polyhydroxyalkanoate as a potential material for ligament and tendon scaffold material. J Biomed Mater Res A 93:1391–1403PubMedCrossRefGoogle Scholar
  116. Raza ZA, Riaz S, Banat IM (2018) Polyhydroxyalkanoates: properties and chemical modification approaches for their functionalization. Biotechnol Prog 34:29–41PubMedCrossRefGoogle Scholar
  117. Ren Y, Wang C, Qiu Y (2008) Aging of surface properties of ultra high modulus polyethylene fibers treated with He/O atmospheric pressure plasma jet. Surf Coat Technol 202:2670–2676CrossRefGoogle Scholar
  118. Ren Q, Ruth K, Thöny-Meyer L, Zinn M (2010) Enatiomerically pure hydroxycarboxylic acids: current approaches and future perspectives. Appl Microbiol Biotechnol 87:41–52PubMedPubMedCentralCrossRefGoogle Scholar
  119. Ricotti L, Polini A, Genchi GG, Ciofani G, Iandolo D, Vazão H, Mattoli V, Ferreira L, Menciassi A, Pisignano D (2012) Proliferation and skeletal myotube formation capability of C2C12 and H9c2 cells on isotropic and anisotropic electrospun nanofibrous PHB scaffolds. Biomed Mater 7:035010PubMedCrossRefGoogle Scholar
  120. Saito T, Tomita K, Juni K, Ooba K (1991) In vivo and in vitro degradation of poly(3-hydroxybutyrate) in rat. Biomaterials 12:309–312PubMedCrossRefGoogle Scholar
  121. Samantaray S, Mallick N (2014) Production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) co-polymer by the diazotrophic cyanobacterium Aulosira fertilissima CCC 444. J Appl Phycol 26:237–245CrossRefGoogle Scholar
  122. Samantaray S, Mallick N (2015) Impact of various stress conditions on poly-β-hydroxybutyrate (PHB) accumulation in Aulosira fertilissima CCC 444. Curr Biotechnol 4:366–372CrossRefGoogle Scholar
  123. Sankhla SS, Bhati R, Singh AK, Mallick N (2010) Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer production from a local isolate, Brevibacillus invocatus MTCC 9039. Biores Technol 101:1947–1953Google Scholar
  124. Schmidt CE, Leach JB (2003) Neural tissue engineering: strategies for repair and regeneration. Ann Rev Biomed Eng 5:293–347CrossRefGoogle Scholar
  125. Sevastianov VI, Perova NV, Shishatskaya EI, Kalacheva GS, Volova TG (2003) Production of purified polyhydroxyalkanoates (PHAs) for applications in contact with blood. J Biomater Sci Polym Ed 14:1029–1042PubMedCrossRefGoogle Scholar
  126. Shah M, Ullah N, Choi MH, Kim MO, Yoon SC (2012) Amorphous amphiphilic P(3HV-co-4HB)-b-mPEG block copolymer synthesized from bacterial copolyester via melt transesterification: nanoparticle preparation, cisplatin loading for cancer therapy and in vitro evaluation. Eur J Pharm Biopharm 80:518–527PubMedCrossRefGoogle Scholar
  127. Shah AA, Kato S, Shintani N, Kamini NR, Nakajima-Kambe T (2014) Microbial degradation of aliphatic and aliphatic-aromatic co-polyesters. Appl Microbiol Biotechnol 98:3437–3447PubMedCrossRefGoogle Scholar
  128. Shangguan YY, Wang YW, Wu Q, Chen GQ (2006) The mechanical properties and in vitro biodegradation and biocompatibility of UV-treated poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). Biomaterials 27:2349–2357PubMedCrossRefGoogle Scholar
  129. Sharma L, Panda B, Singh AK, Mallick N (2006) Studies on poly-β-hydroxybutyrate synthase activity of Nostoc muscorum. J Gen Appl Microbiol 52:209–214PubMedCrossRefGoogle Scholar
  130. Sharma L, Singh AK, Panda B, Mallick N (2007) Process optimization for poly-β-hydroxybutyrate production in a nitrogen fixing cyanobacterium, Nostoc muscorum using response surface methodology. Bioresour Technol 98:987–993PubMedCrossRefGoogle Scholar
  131. Sharma L, Srivastava JK, Singh AK (2016) Biodegradable polyhydroxyalkanoate thermoplastics substituting xenobiotic plastics: a way forward for sustainable environment. In: Singh A, Prasad SM, Singh RP (eds) Plant responses to xenobiotics. Springer-Verlag, New York, pp 317–346CrossRefGoogle Scholar
  132. Shen F, Zhang E, Wei Z (2010) In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) and the influence of surface modification by alkali treatment. Mater Sci Eng C 30:369–375CrossRefGoogle Scholar
  133. Shishatskaya EI, Volova TG, Gitelson II (2002) In vivo toxicological evaluation of polyhydroxyalkanoates. Dokl Biol Sci 383:109–111PubMedCrossRefGoogle Scholar
  134. Shishatskaya EI, Volova TG, Puzyr AP, Mogilnaya OA, Efremov SN (2004) Tissue response to the implantation of biodegradable polyhydroxyalkanoate sutures. J Mater Sci Mater Med 15:719–728PubMedCrossRefGoogle Scholar
  135. Shishatskaya EI, Volova TG, Gordeev SA, Puzyr AP (2005) Degradation of P(3HB) and P(3HB-co-3HV) in biological media. J Biomater Sci Polymer Edn 16:643–657CrossRefGoogle Scholar
  136. Shrivastav A, Kim HY, Kim YR (2013) Advances in the applications of polyhydroxyalkanoate nanoparticles for novel drug delivery system. Biomed Res Int 2013:581684PubMedPubMedCentralCrossRefGoogle Scholar
  137. Singh AK, Mallick N (2008) Enhanced production of SCL-LCL-PHA co-polymer by sludge-isolated Pseudomonas aeruginosa MTCC 7925. Lett Appl Microbiol 46:350–357PubMedCrossRefGoogle Scholar
  138. Singh AK, Mallick N (2009a) Exploitation of inexpensive substrates for production of a novel SCL-LCL-PHA co-polymer by Pseudomonas aeruginosa MTCC 7925. J Ind Microbiol Biotechnol 36:347–354PubMedCrossRefGoogle Scholar
  139. Singh AK, Mallick N (2009b) SCL-LCL-PHA copolymer production by a local isolate, Pseudomonas aeruginosa MTCC 7925. Biotechnol J 4:703–711PubMedCrossRefGoogle Scholar
  140. Singh AK, Mallick N (2016) Biological system as reactor for production of biodegradable thermoplastics, polyhydroxyalkanoates. In: Thangadurai D, Sangeetha J (eds) Industrial biotechnology: sustainable production and bioresource utilization. CRC Press Taylor and Francis, USA, pp 281–323CrossRefGoogle Scholar
  141. Singh AK, Mallick N (2017) Advances in cyanobacterial polyhydroxyalkanoates production. FEMS Microbiol Lett 364(20).
  142. Singh AK, Bhati R, Samantaray S, Mallick N (2013a) Pseudomonas aeruginosa MTCC 7925: producer of a novel SCL-LCL-PHA co-polymer. Curr Biotechnol 2:81–88CrossRefGoogle Scholar
  143. Singh M, Kumar P, Patel SKS, Kalia VC (2013b) Production of polyhydroxyalkanoate co-polymer by Bacillus thuringiensis. Indian J Microbiol 53:77–83PubMedCrossRefGoogle Scholar
  144. Singh AK, Ranjana B, Mallick N (2015) Pseudomonas aeruginosa MTCC 7925 as a biofactory for production of the novel SCL-LCL-PHA thermoplastic from non-edible oils. Curr Botechnol 4:65–74CrossRefGoogle Scholar
  145. Singh AK, Sharma L, Mallick N, Mala J (2017) Progress and challenges in producing polyhydroxyalkanoate biopolymers from cyanobacteria. J Appl Phycol 29:1213–1232CrossRefGoogle Scholar
  146. Singh AK, Sharma L, Srivastava JK, Mallick N, Ansari MI (2018) Microbially originated polyhydroxyalkanoate (PHA) biopolymers: an insight into the molecular mechanism and biogenesis of PHA granules. In: Singh OV, Chandel AK (eds) Sustainable biotechnology-enzymatic resources of renewable energy. Springer, Cham, pp 355–398CrossRefGoogle Scholar
  147. Sodian R, Hoerstrup SP, Sperling JS, Daebritz S, Martin DP, Moran AM, Kim BS, Schoen FJ, Vacanti JP, Mayer JE Jr (2000) Early in vivo experience with tissue-engineered trileaflet heart valves. Circulation 102:III22–III29PubMedCrossRefGoogle Scholar
  148. Sreekanth MS, Vijayendra SV, Joshi GJ, Shamala TR (2013) Effect of carbon and nitrogen sources on simultaneous production of a-amylase and green food packaging polymer by Bacillus sp. CFR 67. J Food Sci Technol 50:404–408PubMedCrossRefGoogle Scholar
  149. Steinbüchel A (1991) Polyhydroxyalkanoic acids. In: Byrom D (ed) Biomaterials: novel materials from biological sources. Stockton, New York, pp 124–213Google Scholar
  150. Stock UA, Degenkolbe I, Attmann T, Schenke-Layland K, Freitag S, Lutter G (2006) Prevention of device-related tissue damage during percutaneous deployment of tissue-engineered heart valves. J Thorac Cardiovasc Surg 131:1323–1330PubMedCrossRefGoogle Scholar
  151. Tang S, Ai Y, Dong Z, Yang Q (1999) Tissue response to subcutaneous implanting poly-3-hydroxybutyrate in rats. Disi Junyi Daxue Xuebao 20:87–89Google Scholar
  152. Tezcaner A, Bugra K, Hasirci V (2003) Retinal pigment epithelium cell culture on surface modified poly(hydroxybutyrate-co-hydroxyvalerate) thin films. Biomaterials 24:4573–4583PubMedCrossRefGoogle Scholar
  153. Tokiwa Y, Calabia BP (2004) Degradation of microbial polyesters. Biotechnol Lett 26:1181–1189PubMedCrossRefGoogle Scholar
  154. Turesin F, Gursel I, Hasirci V (2001) Biodegradable polyhydroxyalkanoate implants for osteomyelitis therapy: in vitro antibiotic release. J Biomater Sci Polym Edn 12:195–207Google Scholar
  155. Ueda H, Tabata Y (2003) Polyhydroxyalkanonate derivatives in current clinical applications and trials. Adv Drug Deliv Rev 55:501–518PubMedCrossRefGoogle Scholar
  156. Urtuvia V, Villegas P, González M, Seeger M (2014) Bacterial production of the biodegradable plastics polyhydroxyalkanoates. Int J Biol Macromol 70:208–213PubMedCrossRefGoogle Scholar
  157. US Department of Health and Human Services, FDA (1997) Guidance for industry. Rockville, p 54Google Scholar
  158. Valappil SP, Misra SK, Boccaccini AR, Roy I (2006) Biomedical applications of polyhydroxyalkanoates: an overview of animal testing and in vivo responses. Expert Rev Med Devices 3:853–868PubMedCrossRefGoogle Scholar
  159. Vieyra H, Juárez E, López UF, Morales AG, Torres M (2018) Cytotoxicity and biocompatibility of biomaterials based in polyhydroxybutyrate reinforced with cellulose nanowhiskers determined in human peripheral leukocytes. Biomed Mater 13:045011PubMedCrossRefGoogle Scholar
  160. Volova T, Goncharov D, Sukovatyi A, Shabanov A, Nikolaeva E, Shishatskaya E (2013) Electrospinning of polyhydroxyalkanoate fibrous scaffolds: effects on electrospinning parameters on structure and properties. J Biomater Sci Polym Edn 25:370–393CrossRefGoogle Scholar
  161. Volova TG, Shishatskaya EI, Nikolaeva ED, Sinskey A (2014) In vivo study of 2D PHA matrices of different chemical compositions: tissue reactions and biodegradations. J Mater Sci Technol 30:549–557CrossRefGoogle Scholar
  162. Wang YW, Wu Q, Chen GQ (2003) Reduced mouse fibroblast cell growth by increased hydrophilicity of microbial polyhydroxyalkanoates via hyaluronan coating. Biomaterials 24:4621–4629PubMedCrossRefGoogle Scholar
  163. Wang YW, Wu Q, Chen GQ (2004) Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds. Biomaterials 25:669–675PubMedCrossRefGoogle Scholar
  164. Wang YW, Yang F, Wu Q, Cheng YC, Yu PHF, Chen J, Chen GQ (2005) Effect of composition of poly(3-hydroxybutyrate-co-3hydroxyhexanoate) on growth of fibroblast and osteoblast. Biomaterials 26:755–761PubMedCrossRefGoogle Scholar
  165. Wang B, Pugh S, Nielsen DR, Zhang W, Meldrum DR (2013a) Engineering cyanobacteria for photosynthetic production of 3-hydroxybutyrate directly from CO2. Metab Eng 16:68–77PubMedCrossRefGoogle Scholar
  166. Wang Y, Jiang XL, Peng SW, Guo XY, Shang GG, Chen JC, Wu Q, Chen GQ (2013b) Induced apoptosis of osteoblasts proliferating on polyhydroxyalkanoates. Biomaterials 34:3737–3746PubMedCrossRefGoogle Scholar
  167. Wang Y, Yin J, Chen GQ (2014) Polyhydroxyalkanoates, challenges and opportunities. Curr Opin Biotechnol 30:59–65PubMedCrossRefGoogle Scholar
  168. Weber B, Scherman J, Emmert MY, Gruenenfelder J, Verbeek R, Bracher M, Black M, Kortsmit J, Franz T, Schoenauer R, Baumgartner L, Brokopp C, Agarkova I, Wolint P, Zund G, Falk V, Zilla P, Hoerstrup SP (2011) Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates. Eur Heart J 32:2830–2840PubMedCrossRefGoogle Scholar
  169. Wei X, Hu YJ, Xie WP, Lin RL, Chen GQ (2009) Influence of poly(3hydroxybutyrate-co-4-hydroxybutyrate-co-3-hydroxyhexanoate) on growth and osteogenic differentiation of human bone marrow derived mesenchymal stem cells. J Biomed Mater Res A 90:894–905PubMedCrossRefGoogle Scholar
  170. Wei DX, Dao JW, Chen GQ (2018) A micro-ark for cells: highly open porous polyhydroxyalkanoate microspheres as injectable scaffolds for tissue regeneration. Adv Mater 30:e1802273PubMedCrossRefGoogle Scholar
  171. Williams SF, Martin DP, Horowitz DM, Peoples OP (1999) PHA applications: addressing the price performance issue: I. Tissue engineering. Int J Biol Macromol 25:111–121PubMedCrossRefGoogle Scholar
  172. Williams SF, Martin DP, Gerngross T, Horowitz DM (2001) Removing endotoxin with an oxidizing agent from polyhydroxyalkanoates produced by fermentation. US Patent No 6245537Google Scholar
  173. Winnacker M, Rieger B (2017) Copolymers of polyhydroxyalkanoates and polyethylene glycols: recent advancements with biological and medical significance. Polym Int 66:497–503CrossRefGoogle Scholar
  174. Wu Q, Wang Y, Chen GQ (2009) Medical application of microbial biopolyesters polyhydroxyalkanoates. Artif Cells Blood Substit Immobil Biotechnol 37:1–12PubMedCrossRefGoogle Scholar
  175. Xu XY, Li XT, Peng SW, Xiao JF, Liu C, Fang G, Chen KC, Chen GQ (2010) The behaviour of neural stem cells on polyhydroxyalkanoate nanofiber scaffolds. Biomaterials 31:3967–3975PubMedCrossRefGoogle Scholar
  176. Xu M, Qin J, Rao Z, You H, Zhang X, Yang T, Wang X, Xu Z (2016) Effect of Polyhydroxybutyrate (PHB) storage on L-arginine production in recombinant Corynebacterium crenatum using coenzyme regulation. Microb Cell Factories 15:15–26CrossRefGoogle Scholar
  177. Xue Q, Liu XB, Lao YH, Wu LP, Wang D, Zuo ZQ, Chen JY, Hou J, Bei YY, Wu XF, Leong KW, Xiang H, Han J (2018) Anti-infective biomaterials with surface-decorated tachyplesin I. Biomaterials 178:351–362Google Scholar
  178. Yan C, Wang Y, Shen XY, Yang G, Jian J, Wang HS, Chen GQ, Wu Q (2011) MicroRNA regulation associated chondrogenesis of mouse MSCs grown on polyhydroxyalkanoates. Biomaterials 32:6435–6444PubMedCrossRefGoogle Scholar
  179. Yang X, Zhao K, Chen GQ (2002) Effect of surface treatment on the biocompatibility of microbial polyhydroxyalkanoates. Biomaterials 23:1391–1397PubMedCrossRefGoogle Scholar
  180. Yang Y, De Laporte L, Rives CB, Jang J-H, Lin W-C, Shull KR, Shea LD (2005) Neurotrophin releasing single and multiple lumen nerve conduits. J Control Release 104:433–446PubMedPubMedCentralCrossRefGoogle Scholar
  181. Yang XD, Li HM, Chen M, Zou XH, Zhu LY, Wei CJ, Chen GQ (2010) Enhanced insulin production from murine islet beta cells incubated on poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). J Biomed Mater Res A 92:548–555PubMedGoogle Scholar
  182. Ye H, Zhang K, Kai D, Li Z, Loh XJ (2018) Polyester elastomers for soft tissue engineering. Chem Soc Rev 47:4545–4580PubMedCrossRefGoogle Scholar
  183. Young RC, Wiberg M, Terenghi G (2002) Poly-3-hydroxybutyrate (PHB): a resorbable conduit for long-gap repair in peripheral nerves. Br J Plast Surg 55:235–240PubMedCrossRefGoogle Scholar
  184. Yue H, Ling C, Yang T, Chen X, Chen Y, Deng H, Wu Q, Chen J, Chen G-Q (2014) A seawater-based open and continuous process for polyhydroxyalkanoates production by recombinant Halomonas campaniensis LS21 grown in mixed substrates. Biotechnol Biofuels 7:108CrossRefGoogle Scholar
  185. Zembouai I, Kaci M, Bruzaud S, Benhamida A, Corre YM, Grohens Y (2013) A study of morphological, thermal, rheological and barrier properties of poly (3-hydroxybutyrate-co-3Hydroxyvalerate)/polylactide blends prepared by melt mixing. Polym Test 32:842–851CrossRefGoogle Scholar
  186. Zhang J, Cao Q, Li S, Lu X, Zhao Y, Guan JS, Chen JC, Wu Q, Chen GQ (2013) 3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer's disease via mitochondria protection mechanism. Biomaterials 34:7552–7562PubMedCrossRefGoogle Scholar
  187. Zhang J, Shishatskaya EI, Volova TG, da Silva LF, Chen GQ (2018) Polyhydroxyalkanoates (PHA) for therapeutic applications. Mater Sci Eng C Mater Biol Appl 86:144–150PubMedCrossRefGoogle Scholar
  188. Zhao K, Yang X, Chen GQ, Chen JC (2002) Effect of lipase treatment on the biocompatibility of microbial polyhydroxyalkanoates. J Mater Sci-Mater M 13:849–854CrossRefGoogle Scholar
  189. Zhao K, Deng Y, Chen JC, Chen GQ (2003a) Polyhydroxyalkanoate (PHA) scaffolds with good mechanical properties and biocompatibility. Biomaterials 24:1041–1045PubMedCrossRefGoogle Scholar
  190. Zhao K, Deng Y, Chen GQ (2003b) Effects of surface morphology on the biocompatibility of polyhydroxyalkanoates. Biochem Eng J 16:115–123CrossRefGoogle Scholar
  191. Zhao Y, Zou B, Shi Z, Wu Q, Chen G-Q (2007) The effect of 3-hydroxybutyrate on the in vitro differentiation of murine osteoblast MC3T3-E1 and in vivo bone formation in ovariectomized rats. Biomaterials 28:3063–3073PubMedCrossRefGoogle Scholar
  192. Zhao H, Cui Z, Sun X, Turng HL, Peng X (2013) Morphology and properties of injection molded solid and microcellular polylactic acid/polyhydroxybutyrate-valerate (PLA/PHBV) blends. Ind Eng Chem Res 52:2569–2581CrossRefGoogle Scholar
  193. Zhou L, Chen Z, Chi W, Yang X, Wang W, Zhang B (2012) Mono-methoxy-poly(3-hydroxybutyrate-co-4-hydroxybutyrate)-graft-hyper-branched polyethylenimine copolymers for siRNA delivery. Biomaterials 33:2334–2344PubMedCrossRefGoogle Scholar
  194. Zinn M, Witholt B, Egli T (2001) Occurrence, synthesis and medical application of bacterial polyhydroxyalkanoate. Adv Drug Deliv Rev 53:5–21PubMedCrossRefGoogle Scholar
  195. Zubairi SI, Mantalaris A, Bismarck A, Aizad S (2016) Polyhydroxyalkanoates (PHAs) for tissue engineering applications: biotransformation of palm oil mill effluent (POME) to value-added polymers. J Teknol 78:13–29Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Amity Institute of BiotechnologyAmity University Uttar Pradesh, Lucknow CampusLucknowIndia
  2. 2.Department of Biotechnology, Engineering School of Lorena (EEL)University of São PauloLorenaBrazil
  3. 3.Department of HorticultureSikkim UniversityGangtokIndia
  4. 4.Agricultural and Food Engineering DepartmentIndian Institute of TechnologyKharagpurIndia

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