Polyhydroxyalkanoates (PHA) – Applications in Wound Treatment and as Precursors for Oral Drugs

  • Larissa de Souza
  • Srividya ShivakumarEmail author


Polyhydroxyalkanoates (PHA) are a family of thermoplastic linear polymers that are naturally synthesized by microbes which is an alternate nutrient (carbon) source, utilized during unfavourable conditions. PHA possess numerous important qualities like bio-compatibility, biodegradability, etc. which allows its safe usage, especially in the medical and environmental sectors. This chapter addresses the recent advancements accomplished in the last decade for the potential utilization of PHA in two specific avenues in the medical field: (1) for skin and wound healing treatment and (2) as precursors for oral drugs production. The advantages of utilizing PHA as biomaterials in medical devices are innumerable. Biomaterials are substances of either natural or artificial origin which are designed for its utilization in medically treating a biological system. In addition to biocompatibility, PHA have mechanical stability, strength, structure like extracellular matrix (ECM), non-toxic degradation products, etc. which make it highly desirable for medical applications. In their natural form, PHA lack antimicrobial properties and are non-antigenic. However, studies have shown that certain degradation products of PHA hydrolysis can evoke an inhibitory effect on microbial growth. In addition, numerous reports of chemically incorporating antibiotics, metal nanoparticles, etc. onto a PHA film can generate a composite blend that has antimicrobial properties. PHA are composed of monomers made up of 3-hydroyalkanoic acids (3-HA) and as they are enantiomerically pure, PHA constitute an untapped source of chiral building blocks which can be used for the manufacture of oral drugs. The ease with which these chiral molecules can be obtained from PHA through the action of dehydrogenases and hydrolases in addition to direct biosynthesis by microbes, makes this a viable and eco-friendly method as compared to chemical synthesis which involves the usage of harsh reaction conditions and chemicals. It is evident from the quantity of studies being conducted in these avenues, that PHA application as antimicrobial wound dressings and as oral drug precursors has great potential and scope.


Polyhydroxyalkanoates Biomaterials 3-hydroxy acids Drug precursors Wound dressings Skin healing 


  1. Alavi S, Thomas S, Sandeep KP, Kalarikkal N, Varghese J, Yaragalla S (2014) Polymers for packaging applications. CRC Press, Boca Raton, 459 pCrossRefGoogle Scholar
  2. Anderson AJ, Dawes EA (1990) Occurrence, metabolism, metabolic role, and industrial uses of bacterial polyhydroxyalkanoates. Microbiol Rev 54:450–472PubMedPubMedCentralGoogle Scholar
  3. Asran AS, Razghandi K, Aggarwal N, Michler GH, Groth T (2010) Nanofibers from blends of polyvinyl alcohol and polyhydroxy butyrate as potential scaffold material for tissue engineering of skin. Biomacromolecules 11:3413–3421. PubMedCrossRefGoogle Scholar
  4. Babu RP, O’Connor K, Seeram R (2013) Current progress on bio-based polymers and their future trends. Prog Biomater 2:8. PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bacakova L, Novotná K, Parizek M (2014) Polysaccharides as cell carriers for tissue engineering: the use of cellulose in vascular wall reconstruction. Physiol Res Suppl 1:S29–S47Google Scholar
  6. Brigham CJ, Sinskey AJ (2012) Applications of polyhydroxyalkanoates in the medical industry. Int J Biotechnol Wellness Ind 1:52–60. CrossRefGoogle Scholar
  7. Brown HC, Ramachandran PV (1991) The boron approach to asymmetric synthesis. Pure Appl Chem 63:307–316. CrossRefGoogle Scholar
  8. Bunster GF (2015) Polyhydroxyalkanoates: production and use. In: Mishra M (ed) Encyclopedia of biomedical polymers and polymeric biomaterials. CRC Press, Boca Raton, pp 6412–6421. isbn:9781439898796CrossRefGoogle Scholar
  9. Calabia BP, Tokiwa Y (2006) A novel PHB depolymerase from a thermophilic Streptomyces sp. Biotechnol Lett 28:383–388. PubMedCrossRefGoogle Scholar
  10. Chattopadhyay S, Raines RT (2014) Review collagen-based biomaterials for wound healing. Biopolymers 101:821–833. PubMedPubMedCentralCrossRefGoogle Scholar
  11. Chen GQ, Wu Q (2005a) Microbial production and applications of chiral hydroxyalkanoates. Appl Microbiol Biotechnol 67:592–599. PubMedCrossRefGoogle Scholar
  12. Chen GQ, Wu Q (2005b) The application of polyhydroxyalkanoates as tissue engineering materials. Biomaterials 26:6565–6578. PubMedCrossRefGoogle Scholar
  13. Chen CW, Don TM, Yen HF (2006) Enzymatic extruded starch as a carbon source for the production of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) by Haloferax mediterranei. Process Biochem 41:2289–2296. CrossRefGoogle Scholar
  14. Chung A, Liu Q, Ouyang SP, Wu Q, Chen GQ (2009) Microbial production of 3-hydroxydodecanoic acid by PHA operon and fadBA knockout mutant of Pseudomonas putida KT2442 harboring tesB gene. Appl Microbiol Biotechnol 83:513–519. PubMedCrossRefGoogle Scholar
  15. Chung AL, Zeng GD, Jin HL, Wu Q, Chen JC, Chen GQ (2013) Production of medium-chain-length 3-hydroxyalkanoic acids by β-oxidation and phaC operon deleted Pseudomonas entomophila harboring thioesterase gene. Metab Eng 17:23–29. PubMedCrossRefGoogle Scholar
  16. de Roo G, Kellerhals MB, Ren Q, Witholt B, Kessler B (2002) Production of chiral R-3-hydroxyalkanoic acids and R-3-hydroxyalkanoic acid methylesters via hydrolytic degradation of polyhydroxyalkanoate synthesized by pseudomonads. Biotechnol Bioeng 77:717–722. PubMedCrossRefGoogle Scholar
  17. Deitzel JM, Kleinmeyer JD, Hirvonen JK, Tan NB (2001) Controlled deposition of electrospun poly (ethylene oxide) fibers. Polymer 42:8163–8170. CrossRefGoogle Scholar
  18. 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 35:14–24. CrossRefGoogle Scholar
  19. Doi Y, Kanesawa Y, Tanahashi N, Kumagai Y (1992) Biodegradation of microbial polyesters in the marine environment. Polym Degrad Stab 36:173–177. CrossRefGoogle Scholar
  20. Dong Y, Hassan WU, Kennedy R, Greiser U, Pandit A, Garcia Y, Wang W (2014) Performance of an in situ formed bioactive hydrogel dressing from a PEG-based hyperbranched multifunctional copolymer. Acta Biomater 10:2076–2085. PubMedCrossRefGoogle Scholar
  21. Eggers J, Steinbüchel A (2013) Poly (3-hydroxybutyrate) degradation in Ralstonia eutropha H16 is mediated stereoselectively to (S)-3-hydroxybutyryl coenzyme A (CoA) via crotonyl-CoA. J Bacteriol 195:3213–3223. PubMedPubMedCentralCrossRefGoogle Scholar
  22. Ekwall B, Silano V, Paganuzzi-Stammati A, Zucco F (1990) Toxicity tests with mammalian cell cultures. In: Bourdeau P, Sommers E, Richardson G, Hickman JR (eds) Short-term toxicity tests for non-genotoxic effects. Wiley, New York, pp 75–99. isbn:978-0471925064CrossRefGoogle Scholar
  23. Eriksen M, Lebreton LC, Carson HS, Thiel M, Moore CJ, Borerro JC, Galgani F, Ryan PG, Reisser J (2014) Plastic pollution in the world’s oceans: more than 5 trillion plastic pieces weighing over 250,000 tons afloat at sea. PLoS One 9:e111913. PubMedPubMedCentralCrossRefGoogle Scholar
  24. Escapa IF, Morales V, Martino VP, Pollet E, Avérous L, García JL, Prieto MA (2011) Disruption of β-oxidation pathway in Pseudomonas putida KT2442 to produce new functionalized PHAs with thioester groups. Appl Microbiol Biotechnol 89:1583–1598. CrossRefGoogle Scholar
  25. Farrar D (2011) Advanced wound repair therapies. Elsevier, New York, 672 pCrossRefGoogle Scholar
  26. Forbes S, McBain AJ, Felton-Smith S, Jowitt TA, Birchenough HL, Dobson CB (2013) Comparative surface antimicrobial properties of synthetic biocides and novel human apolipoprotein E derived antimicrobial peptides. Biomaterials 34:5453–5464. PubMedCrossRefGoogle Scholar
  27. Francis L, Meng D, Locke IC, Knowles JC, Mordan N, Salih V, Boccaccini AR, Roy I (2016) Novel poly (3-hydroxybutyrate) composite films containing bioactive glass nanoparticles for wound healing applications. Polym Int 65:661–674. CrossRefGoogle Scholar
  28. Gallo J, Holinka M, Moucha CS (2014) Antibacterial surface treatment for orthopaedic implants. Int J Mol Sci 15:13849–13880. PubMedPubMedCentralCrossRefGoogle Scholar
  29. Gangoiti J, Santos M, Llama MJ, Serra JL (2010) Production of chiral (R)-3-hydroxyoctanoic acid monomers, catalyzed by Pseudomonas fluorescens GK13 poly (3-hydroxyoctanoic acid) depolymerase. Appl Environ Microbiol 76:3554–3560. PubMedPubMedCentralCrossRefGoogle Scholar
  30. Gao HJ, Wu Q, Chen GQ (2002) Enhanced production of D-(−)-3-hydroxybutyric acid by recombinant Escherichia coli. FEMS Microbiol Lett 213:59–65. PubMedCrossRefGoogle Scholar
  31. Gao G, Lange D, Hilpert K, Kindrachuk J, Zou Y, Cheng JT, Kazemzadeh-Narbat M, Yu K, Wang R, Straus SK, Brooks DE (2011) The biocompatibility and biofilm resistance of implant coatings based on hydrophilic polymer brushes conjugated with antimicrobial peptides. Biomaterials 32:3899–3909. PubMedCrossRefGoogle Scholar
  32. Gowda V, Shivakumar S (2014) Agrowaste-based Polyhydroxyalkanoate (PHA) production using hydrolytic potential of Bacillus thuringiensis IAM 12077. Braz Arch Biol Technol 57:55–61. CrossRefGoogle Scholar
  33. Grass G, Rensing C, Solioz M (2011) Metallic copper as an antimicrobial surface. Appl Environ Microbiol 77:1541–1547. PubMedCrossRefGoogle Scholar
  34. Gray H, Standring S, Anand N, Birch R, Collins P, Crossman AR, Gleeson M, Jawaheer G, Smith AL, Spratt JD, Stringer MD (2016) Gray’s anatomy: the anatomical basis of clinical practice. Elsevier, New York, 1576 pGoogle Scholar
  35. Guevara-Martínez M, Gällnö KS, Sjöberg G, Jarmander J, Perez-Zabaleta M, Quillaguamán J, Larsson G (2015) Regulating the production of (R)-3-hydroxybutyrate in Escherichia coli by N or P limitation. Front Microbiol 6:844. PubMedPubMedCentralCrossRefGoogle Scholar
  36. Gumel AM, Razaif-Mazinah MR, Anis SN, Annuar MS (2015) Poly (3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) hydrogel promotes angiogenesis and collagen deposition during cutaneous wound healing in rats. Biomed Mater 10:045001. PubMedPubMedCentralCrossRefGoogle Scholar
  37. Guo SA, DiPietro LA (2010) Factors affecting wound healing. J Dent Res 89:219–229. PubMedPubMedCentralCrossRefGoogle Scholar
  38. Hann EC, Sigmund AE, Fager SK, Cooling FB, Gavagan JE, Ben-Bassat A, Chauhan S, Payne MS, Hennessey SM, DiCosimo R (2003) Biocatalytic hydrolysis of 3-hydroxyalkanenitriles to 3-hydroxyalkanoic acids. Adv Synth Catal 345:775–782. CrossRefGoogle Scholar
  39. Hazer B, Steinbüchel A (2007) Increased diversification of polyhydroxyalkanoates by modification reactions for industrial and medical applications. Appl Microbiol Biotechnol 74:1–12. PubMedCrossRefGoogle Scholar
  40. Hoenich NA (2007) Cellulose for medical applications: past, present, and future. BioResources 1:270–280Google Scholar
  41. Hoh A, Maier K (1993) Comparative cytotoxicity test with human keratinocytes, HaCaT cells, and skin fibroblasts to investigate skin-irritating substances. In: Bernd A, Bereiter-Hahn J, Hevert F, Holzmann H (eds) Cell and tissue culture models in dermatological research. Springer, Berlin/Heidelberg, pp 341–347. isbn:978-3-642-77819-3CrossRefGoogle Scholar
  42. Holinka J, Pilz M, Kubista B, Presterl E, Windhager R (2013) Effects of selenium coating of orthopaedic implant surfaces on bacterial adherence and osteoblastic cell growth. Bone Joint J 95:678–682. PubMedCrossRefGoogle Scholar
  43. Hölscher T, Breuer U, Adrian L, Harms H, Maskow T (2010) Production of the chiral compound (R)-3-hydroxybutyrate by a genetically engineered methylotrophic bacterium. Appl Environ Microbiol 76:5585–5591. PubMedPubMedCentralCrossRefGoogle Scholar
  44. Hu SG, Jou CH, Yang MC (2003) Protein adsorption, fibroblast activity and antibacterial properties of poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid) grafted with chitosan and chitooligosaccharide after immobilized with hyaluronic acid. Biomaterials 24:2685–2693. PubMedCrossRefGoogle Scholar
  45. Huang TY, Duan KJ, Huang SY, Chen CW (2006) Production of polyhydroxyalkanoates from inexpensive extruded rice bran and starch by Haloferax mediterranei. J Ind Microbiol Biotechnol 33:701–706. PubMedCrossRefGoogle Scholar
  46. Jendrossek D, Handrick R (2002) Microbial degradation of polyhydroxyalkanoates. Annu Rev Microbiol 56:403–432. CrossRefGoogle Scholar
  47. Ji Y, Li XT, Chen GQ (2008) Interactions between a poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) terpolyester and human keratinocytes. Biomaterials 29:3807–3814. PubMedCrossRefGoogle Scholar
  48. Kazemzadeh-Narbat M, Lai BF, Ding C, Kizhakkedathu JN, Hancock RE, Wang R (2013) Multilayered coating on titanium for controlled release of antimicrobial peptides for the prevention of implant-associated infections. Biomaterials 34:5969–5977. PubMedCrossRefGoogle Scholar
  49. Keshel SH, Biazar E, Rezaei Tavirani M, Rahmati Roodsari M, Ronaghi A, Ebrahimi M, Rad H, Sahebalzamani A, Rakhshan A, Afsordeh K (2014) The healing effect of unrestricted somatic stem cells loaded in collagen-modified nanofibrous PHBV scaffold on full-thickness skin defects. Artif Cells Nanomed Biotechnol 42:210–216. PubMedCrossRefGoogle Scholar
  50. Kim JH, Scialli AR (2011) Thalidomide: the tragedy of birth defects and the effective treatment of disease. Toxicol Sci 122:1–6. PubMedCrossRefGoogle Scholar
  51. Kim HW, Chung MG, Rhee YH (2007) Biosynthesis, modification, and biodegradation of bacterial medium-chain-length polyhydroxyalkanoates. J Microbiol 45:87–97PubMedPubMedCentralGoogle Scholar
  52. Koller M, Hesse P, Bona R, Kutschera C, Atlić A, Braunegg G (2007) Biosynthesis of high quality polyhydroxyalkanoate co-and terpolyesters for potential medical application by the archaeon Haloferax mediterranei. In: Slomkowski S (ed) Macromolecular symposia, vol 253. Wiley-VCH Verlag, Weinheim, pp 33–39. CrossRefGoogle Scholar
  53. Koller M, Atlić A, Dias M, Reiterer A, Braunegg G (2010) Microbial PHA production from waste raw materials. In: Chen GQ (ed) Plastics from bacteria. Springer, Berlin/Heidelberg, pp 85–119. isbn:978-3-642-03287-5CrossRefGoogle Scholar
  54. Krishnan V, Lakshmi T (2013) Bioglass: a novel biocompatible innovation. J Adv Pharm Technol Res 4:78–83. PubMedPubMedCentralCrossRefGoogle Scholar
  55. Krüger K, Lang G, Weidner T, Engel AM (1999) Cloning and functional expression of the D-β-hydroxybutyrate dehydrogenase gene of Rhodobacter sp. DSMZ 12077. Appl Microbiol Biotechnol 52:666–669PubMedCrossRefGoogle Scholar
  56. Lee SY, Lee Y (2003) Metabolic engineering of Escherichia coli for production of enantiomerically pure (R)-(−)-hydroxycarboxylic acids. Appl Environ Microbiol 69:3421–3426. PubMedPubMedCentralCrossRefGoogle Scholar
  57. Lee SH, Park SJ, Lee SY, Hong SH (2008) Biosynthesis of enantiopure (S)-3-hydroxybutyric acid in metabolically engineered Escherichia coli. Appl Microbiol Biotechnol 79:633–641. PubMedCrossRefGoogle Scholar
  58. Mano JF, Silva GA, Azevedo HS, Malafaya PB, Sousa RA, Silva SS, Boesel LF, Oliveira JM, Santos TC, Marques AP, Neves NM (2007) Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends. J R Soc Interface 4:999–1030. PubMedPubMedCentralCrossRefGoogle Scholar
  59. Marcano AM, Bou Haidar N, Marais S, Valleton JM, Duncan AC (2017) Designing biodegradable PHA-based 3D scaffolds with antibiofilm properties for wound dressings: optimization of the micro/nanostructure. ACS Biomater Sci Eng 3:3654–3661. CrossRefGoogle Scholar
  60. Martin CH, Dhamankar H, Tseng HC, Sheppard MJ, Reisch CR, Prather KL (2013) A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone. Nat Commun 4:1414. PubMedCrossRefGoogle Scholar
  61. MacNeil S (2007) Progress and opportunities for tissue-engineered skin. Nature 445:874–880. PubMedCrossRefGoogle Scholar
  62. Metcalfe AD, Ferguson MW (2006) Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration. J Royal Soc Interface 4:413–437. CrossRefGoogle Scholar
  63. Noyori R, Kitamura M, Ohkuma T (2004) Toward efficient asymmetric hydrogenation: architectural and functional engineering of chiral molecular catalysts. Proc Natl Acad Sci U S A 101:5356–5362. PubMedPubMedCentralCrossRefGoogle Scholar
  64. Numata K, Abe H, Iwata T (2009) Biodegradability of poly (hydroxyalkanoate) materials. Materials 2:1104–1126. PubMedCentralCrossRefGoogle Scholar
  65. Ong SY, Chee JY, Sudesh K (2017) Degradation of polyhydroxyalkanoate (PHA): a review. J Sib Fed Univ Biol 10:211–225. CrossRefGoogle Scholar
  66. Orita I, Nishikawa K, Nakamura S, Fukui T (2014) Biosynthesis of polyhydroxyalkanoate copolymers from methanol by Methylobacterium extorquens AM1 and the engineered strains under cobalt-deficient conditions. Appl Microbiol Biotechnol 98:3715–3725. PubMedCrossRefGoogle Scholar
  67. Ostomel TA, Shi Q, Tsung CK, Liang H, Stucky GD (2006) Spherical bioactive glass with enhanced rates of hydroxyapatite deposition and hemostatic activity. Small 2:1261–1265. PubMedCrossRefGoogle Scholar
  68. Panáček A, Kolář M, Večeřová R, Prucek R, Soukupová J, Kryštof V, Hamal P, Zbořil R, Kvítek L (2009) Antifungal activity of silver nanoparticles against Candida spp. Biomaterials 30:6333–6340. PubMedCrossRefGoogle Scholar
  69. Park SH, Lee SH, Lee SY (2001) Preparation of optically active β-amino acids from microbial polyester polyhydroxyalkanoates. J Chem Res 2001:498–499. CrossRefGoogle Scholar
  70. Park SJ, Lee SY, Lee Y (2004) Biosynthesis of (R)-3-hydroxyalkanoic acids by metabolically engineered Escherichia coli. Appl Biochem Biotechnol 114:373–379. CrossRefGoogle Scholar
  71. Peschel G, Dahse HM, Konrad A, Wieland GD, Mueller PJ, Martin DP, Roth M (2008) Growth of keratinocytes on porous films of poly (3-hydroxybutyrate) and poly (4-hydroxybutyrate) blended with hyaluronic acid and chitosan. J Biomed Mater Res A 85:1072–1081. PubMedCrossRefGoogle Scholar
  72. Peoples OP, Saunders C, Nichols S, Beach L (1999) Animal nutrition compositions, PCT Patent Applications No. WO. 99:34687Google Scholar
  73. Petrini P, Arciola CR, Pezzali I, Bozzini S, Montanaro L, Tanzi MC, Speziale P, Visai L (2006) Antibacterial activity of zinc modified titanium oxide surface. Int J Artif Organs 29:434–442PubMedCrossRefGoogle Scholar
  74. Poli A, Di Donato P, Abbamondi GR, Nicolaus B (2011) Synthesis, production, and biotechnological applications of exopolysaccharides and polyhydroxyalkanoates by archaea. Archaea 2011:693253. PubMedPubMedCentralCrossRefGoogle Scholar
  75. Pramanik N, Mitra T, Khamrai M, Bhattacharyya A, Mukhopadhyay P, Gnanamani A, Basu RK, Kundu PP (2015) Characterization and evaluation of curcumin loaded guar gum/polyhydroxyalkanoates blend films for wound healing applications. RSC Adv 5:63489–63501. CrossRefGoogle Scholar
  76. Puppi D, Chiellini F, Dash M, Chiellini E (2011) Biodegradable polymers for biomedical applications. In: Felton G (ed) Biodegradable polymers: processing, degradation & applications. Nova Science Publishers, Hauppauge, pp 545–604. isbn:978-1-61209-534-9Google Scholar
  77. Rahmani Del Bakhshayesh A, Annabi N, Khalilov R, Akbarzadeh A, Samiei M, Alizadeh E, Alizadeh-Ghodsi M, Davaran S, Montaseri A (2018) Recent advances on biomedical applications of scaffolds in wound healing and dermal tissue engineering. Artif cells nanomed biotechnol 46:691–705. PubMedCrossRefGoogle Scholar
  78. Rehm BH (2009) Microbial production of biopolymers and polymer precursors: applications and perspectives. Horizon Scientific Press, Poole, 289 pGoogle Scholar
  79. Rehm BH, Steinbüchel A (2002) Polyhydroxyalkanoate (PHA) synthases: the key enzymes of PHA synthesis. Biopolymers Online.
  80. Ren Q, Grubelnik A, Hoerler M, Ruth K, Hartmann R, Felber H, Zinn M (2005) Bacterial poly (hydroxyalkanoates) as a source of chiral hydroxyalkanoic acids. Biomacromolecules 6:2290–2298. PubMedCrossRefGoogle Scholar
  81. Ren Q, Ruth K, Thöny-Meyer L, Zinn M (2010) Enatiomerically pure hydroxycarboxylic acids: current approaches and future perspectives. Appl Microbiol Biotechnol 87:41–52. PubMedPubMedCentralCrossRefGoogle Scholar
  82. Reusch RN, Bryant EM, Henry DN (2003) Increased poly-(R)-3-hydroxybutyrate concentrations in streptozotocin (STZ) diabetic rats. Acta Diabetol 40:91–94. PubMedCrossRefGoogle Scholar
  83. Ruth K, Grubelnik A, Hartmann R, Egli T, Zinn M, Ren Q (2007) Efficient production of (R)-3-hydroxycarboxylic acids by biotechnological conversion of polyhydroxyalkanoates and their purification. Biomacromolecules 8:279–286. PubMedCrossRefGoogle Scholar
  84. Seebach D, Fritz MG (1999) Detection, synthesis, structure, and function of oligo (3-hydroxyalkanoates): contributions by synthetic organic chemists. Int J boil macromol 25:217–236. CrossRefGoogle Scholar
  85. Seebach D, Beck AK, Breitschuh R, Job K (1992) Direct degradation of the biopolymer poly [(R)-3-hydroxybutyric acid] to (R)-3-hydroxybutanoic acid and its methyl ester. Org Synth 1:39Google Scholar
  86. Shishatskaya EI, Nikolaeva ED, Vinogradova ON, Volova TG (2016) Experimental wound dressings of degradable PHA for skin defect repair. J Mater Sci Mater Med 27:165. PubMedPubMedCentralCrossRefGoogle Scholar
  87. Smithells RW, Newman CG (1992) Recognition of thalidomide defects. J Med Genet 29:716–723PubMedPubMedCentralCrossRefGoogle Scholar
  88. Subin R, Bhat SG (2014) Bacterial Polyhydroxyalkanoates production and its applications. In: Bhat SG, Nambisan P (eds) Microbial Bioproducts. Directorate of Public Relations and Publications for Department of Biotechnology, Cochin University of Science and Technology, pp 70–96. ISBN. isbn:978-93-80095-51-6Google Scholar
  89. Suwantong O, Waleetorncheepsawat S, Sanchavanakit N, Pavasant P, Cheepsunthorn P, Bunaprasert T, Supaphol P (2007) In vitro biocompatibility of electrospun poly (3-hydroxybutyrate) and poly (3-hydroxybutyrate-co-3-hydroxyvalerate) fiber mats. Int J Biol Macromol 40:217–223. PubMedCrossRefGoogle Scholar
  90. Tasaki O, Hiraide A, Shiozaki T, Yamamura H, Ninomiya N, Sugimoto H (1999) The dimer and trimer of 3-hydroxybutyrate oligomer as a precursor of ketone bodies for nutritional care. J Parenter Enter Nutr 23:321–325. CrossRefGoogle Scholar
  91. Thakur PS, Borah B, Baruah SD, Nigam JN (2001) Growth-associated production of poly-3-hydroxybutyrate by Bacillus mycoides. Folia Microbiol 46:488–494. CrossRefGoogle Scholar
  92. Therapontos C, Erskine L, Gardner ER, Figg WD, Vargesson N (2009) Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation. Proc Natl Acad Sci U S A 106:8573–8578. PubMedPubMedCentralCrossRefGoogle Scholar
  93. Tieu K, Perier C, Caspersen C, Teismann P, Wu DC, Yan SD, Naini A, Vila M, Jackson-Lewis V, Ramasamy R, Przedborski S (2003) D-β-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J Clin Invest 112:892–901. PubMedPubMedCentralCrossRefGoogle Scholar
  94. Tran PA, Webster TJ (2011) Selenium nanoparticles inhibit Staphylococcus aureus growth. Int J Nanomed 6:1553–1558. CrossRefGoogle Scholar
  95. Tseng HC, Martin CH, Nielsen DR, Prather KL (2009) Metabolic engineering of Escherichia coli for enhanced production of (R)-and (S)-3-hydroxybutyrate. Appl Environ Microbiol 75:3137–3145. PubMedPubMedCentralCrossRefGoogle Scholar
  96. Tseng HC, Harwell CL, Martin CH, Prather KL (2010) Biosynthesis of chiral 3-hydroxyvalerate from single propionate-unrelated carbon sources in metabolically engineered E. coli. Microb Cell Factories 9:96. CrossRefGoogle Scholar
  97. Uchino K, Saito T, Gebauer B, Jendrossek D (2007) Isolated poly (3-hydroxybutyrate) (PHB) granules are complex bacterial organelles catalyzing formation of PHB from acetyl coenzyme A (CoA) and degradation of PHB to acetyl-CoA. J Bacteriol 189:8250–8256. PubMedPubMedCentralCrossRefGoogle Scholar
  98. Ugwu CU, Tokiwa Y, Aoyagi H, Uchiyama H, Tanaka H (2008) UV mutagenesis of Cupriavidus necator for extracellular production of (R)-3-hydroxybutyric acid. J Appl Microbiol 105:236–242. PubMedCrossRefGoogle Scholar
  99. Ulery BD, Nair LS, Laurencin CT (2011) Biomedical applications of biodegradable polymers. J Polym Sci B Polym Phys 49:832–864. PubMedPubMedCentralCrossRefGoogle Scholar
  100. Vigneswari S, Lee TS, Bhubalan K, Amirul AA (2015) Extracellular polyhydroxyalkanoate depolymerase by Acidovorax sp. DP5. Enzym Res 2015:212159. CrossRefGoogle Scholar
  101. Vigneswari S, Murugaiyah V, Kaur G, Khalil HA, Amirul AA (2016a) Biomacromolecule immobilization: grafting of fish-scale collagen peptides onto aminolyzed P (3HB-co-4HB) scaffolds as a potential wound dressing. Biomed Mater 11:055009. PubMedCrossRefGoogle Scholar
  102. Vigneswari S, Murugaiyah V, Kaur G, Khalil HA, Amirul AA (2016b) Simultaneous dual syringe electrospinning system using benign solvent to fabricate nanofibrous P(3HB-co-4HB)/collagen peptides construct as potential leave-on wound dressing. Mater Sci Eng C 66:147–155. CrossRefGoogle Scholar
  103. Wang Q, Webster TJ (2012) Nanostructured selenium for preventing biofilm formation on polycarbonate medical devices. J Biomed Mater Res A 100:3205–3210. PubMedCrossRefGoogle Scholar
  104. Williams SF, Martin DP (2002) Applications of PHAs in medicine and pharmacy. Biopolymers Online 4:91–103. CrossRefGoogle Scholar
  105. Wu Q, Zheng Z, Xi JZ, Gao H, Chen GQ (2003) Production of hydroxyalkanoate monomers by microbial fermentation. J Chem Eng Jpn 36:1170–1173. CrossRefGoogle Scholar
  106. Yadav P, Yadav H, Shah VG, Shah G, Dhaka G (2015) Biomedical biopolymers, their origin and evolution in biomedical sciences: a systematic review. J Clin Diagn Res 9:ZE21–ZE25. PubMedPubMedCentralCrossRefGoogle Scholar
  107. Yuan MQ, Shi ZY, Wei XX, Wu Q, Chen SF, Chen GQ (2008) Microbial production of medium-chain-length 3-hydroxyalkanoic acids by recombinant Pseudomonas putida KT2442 harboring genes fadL, fadD and phaZ. FEMS Microbiol Lett 283:167–175. PubMedCrossRefGoogle Scholar
  108. Zhao K, Tian G, Zheng Z, Chen JC, Chen GQ (2003) Production of D-(−)-3-hydroxyalkanoic acid by recombinant Escherichia coli. FEMS Microbiol Lett 218:59–64. PubMedCrossRefGoogle Scholar
  109. Zheng Z, Zhang MJ, Zhang G, Chen GQ (2004) Production of 3-hydroxydecanoic acid by recombinant Escherichia coli HB101 harboring phaG gene. Antonie Van Leeuwenhoek 85:93–101. PubMedCrossRefGoogle Scholar
  110. Zhou J, Peng SW, Wang YY, Zheng SB, Wang Y, Chen GQ (2010) The use of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds for tarsal repair in eyelid reconstruction in the rat. Biomaterials 31:7512–7518. CrossRefGoogle Scholar
  111. Zine R, Sinha M (2015) Nanofibrous poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/collagen/graphene oxide scaffolds for wound coverage. Mater Sci Eng C 80:129–134. CrossRefGoogle Scholar
  112. Zinn M, Witholt B, Egli T (2001) Occurrence, synthesis and medical application of bacterial polyhydroxyalkanoate. Adv Drug Deliv Rev 53:5–21. PubMedPubMedCentralCrossRefGoogle Scholar
  113. Zonari A, Cerqueira MT, Novikoff S, Goes AM, Marques AP, Correlo VM, Reis RL (2014) Poly(hydroxybutyrate-co-hydroxyvalerate) bilayer skin tissue engineering constructs with improved epidermal rearrangement. Macromol Biosci 14:977–990. PubMedCrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Microbiology, School of Sciences (SoS) Centre for PG StudiesJain UniversityBangaloreIndia

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