Biomedical Applications of Bioplastics
Authors: Vipin Chandra Kalia and Subhasree Ray
Plastics, the synthetic polymers are an integral part of our daily life. Incidentally, their excessive use has resulted in their accumulation in the environment and are becoming difficult to manage. The major reason is their non-biodegradable nature. Biodegradable plastics or bioplastics are produce by certain bacteria through a unique metabolic route. Bioplastics especially, polyhydroxyalkanoates (PHAs) are finding their applications in the field of medicine because they are biodegradable, biocompatible, and non-toxic. PHAs can be used as biocontrol agents, carriers of drugs, implants, engineering tissue, enhancing memory and inhibiting cancerous growth.
PHA metabolism leads to the production of 3Hydoxy acids (3HAs). Pseudomonas fluorescens possess depolymerase to produce monomers from PHAs, which can be used for synthesizing antimicrobial compounds in the pharmaceutical companies. Transformation of 3HAs in to hydroxycarboxylic acids: 2-alkylated 3HB and β-lactones, act as oral drugs and as carbapenem or macrolide antibiotics against infections caused by Staphylococcus aureus. 3HAs - D-peptide combination acts against cancers. P3HB and P4HB have strong role in skin and wound healing.
Antibiotics at low doses are used as feed supplement for livestock and aquaculture. However, regular usage of antibiotics is likely to disturb the gastrointestinal microflora, which may also develop resistance to them. PHAs being biopolymers of β-hydroxy lower-chain fatty acids, can generated in the intestine by bacteria. These fatty acids have been reported to act as anti-pathogenic for giant tiger prawn.
Carriers for drugs
Drug delivery within the body is an important factor in improving their efficiency. Thus their targeted delivery is a desirable feature. PHAs as biomaterials, are used to producing nano-particles, scaffolds for eluting drugs and tablets. Monomers like 3HB are helpful in synthesizing novel biodegradable polymers like Dendrimers, and have surface-functional moieties and monodispersity. These properties enable them to act as drug carriers - tamsulosin, ketoprofen and clonidine. PHA microspheres loaded with rifampicin act as hemoembolizing agent and as drug carriers. Implantable rods prepared from PHA and its co-polymers are good for delivery of antibiotics.
PHAs modified chemically can be used in tissue engineering, using them for therapeutic and medical purposes: (i) nerve tissue, (ii) cardio-vascular valves, and(iii) grafts. Chemically modified PHAs can be used as screws, pins, sutures, films, and employed as scaffolds for engineering liver tissue and cartilage repair.
PHAs as medical devices are biodegradable, biocompatible, and strong. They are resistant to infections, lack immunogenicity and are non-toxic. A few potential devices include orthopedic pins, cartilage repair, rivets and tacks, cardiovascular grafting, meniscus repair, stents, staples, repair patch, mesh, sutured fastener. PHA sheets coated with lysozyme prevent biofilm formation and prove helpful in wound dressing.
PHAs act as undergo rapid diffusion and prevent brain damage, improve cardiac efficiency by generating energy. The monomers like 3HB can cure diseases such as Parkinson and Alzheimer, by preventing neuronal cell death. 3HB improves calcium deposition, as it has anti-osteoporosis activity.
Memory loss is common among dementia - Alzheimer's disease. To prevent these diseases, modifications of monomers i.e., methyl esters of 3-hydroxybutyrate can act as drug molecules. It protects mitochondrial damage. HA can stimulate Ca2+ channels, to help memory enhancement.
1. Camberos-Luna L, Gerónimo-Olvera C, Montiel T, Rincon-Heredia R, Massieu L (2016) The ketone body, β-Hydroxybutyrate stimulates the autophagic flux and prevents neuronal death induced by glucose deprivation in cortical cultured neurons. Neurochem Res 41:600-609. doi: 10.1007/s11064-015-1700-4
2. Ching KY, Andriotis OG, Li S, Basnett P, Su B, Roy I, Stolz M (2016) Nanofibrous poly (3-hydroxybutyrate)/poly (3-hydroxyoctanoate) scaffolds provide a functional microenvironment for cartilage repair. J Biomater Appl 31:77-91. doi: 10.1177/0885328216639749
3. Defoirdt T, Boon N, Sorgeloos P, Verstraete W, Bossier P (2009) Short-chain fatty acids and poly-β-hydroxyalkanoates: (New) Biocontrol agents for a sustainable animal production. Biotechnol Adv 27:680-685. doi: 10.1016/j.biotechadv.2009.04.026
4. Dinjaski N, Fernandez-Gutierrez M, Selvam S, Parra-Ruiz FJ, Lehman SM, San Roman J, Garcia E, Garcia JL, Garcia AJ Prieto MA (2014) PHACOS, a functionalized bacterial polyester with bactericidal activity against methicillin-resistant Staphylococcus aureus. Biomaterials 35:14-24. doi: 10.1016/j.biomaterials.2013.09.059
5. Gallo J, Holinka M, Moucha CS (2014) Antibacterial surface treatment for orthopaedic implants. Int J Mol Sci 15:13849-13880. doi:10.3390/ijms150813849
6. Goonoo N, Bhaw-Luximon A, Passanha P, Esteves SR, Jhurry D (2016) Third generation poly(hydroxyacid) composite scaffolds for tissue engineering. J Biomed Mater Res Part B 1−18. doi: 10.1002/jbm.b.33674
7. Hazer DB, Kılıçay E, Hazer B (2012) Poly(3-hydroxyalkanoate)s: Diversification and biomedical applications: A state of the art review. Mater Sci Eng C32: 637–647. doi: 10.1016/j.msec.2012.01.021
8. Insomphun C, Chuah JA, Kobayashi S, Fujiki T, Numata K (2016) Influence of hydroxyl groups on the cell viability of polyhydroxyalkanoate (PHA) scaffolds for tissue engineering. ACS Biomater Sci Eng doi: 10.1021/acsbiomaterials.6b00279
9. Kalia VC, Prakash J, Koul S (2016) Biorefinery for glycerol rich biodiesel industry waste. Indian J Microbiol 56:113-125. doi: 10.1007/s12088-016-0583-7
10. Ke Y, Zhang XY, Ramakrishna S, He LM, Wu G (2017) Reactive blends based on polyhydroxyalkanoates: Preparation and biomedical application. Mater Sci Eng C Mater Biol Appl 70:1107-1119. doi: 10.1016/j.msec.2016.03.114
11. Kehail AA, Brigham CJ (2017) Anti-biofilm activity of solvent-cast and electrospun polyhydroxyalkanoate membranes treated with lysozyme. J Polym Environ 1-7. doi: 10.1007/s10924-016-0921-1
12. Koller M, Marsalek L, de Sousa Dias MM, Braunegg G (2016) Producing microbial polyhydroxyalkanoate (PHA) biopolyesters in a sustainable manner. New Biotechnol 37:24-38 doi: 10.1016/j.nbt.2016.05.001
13. Kumar P, Mehariya S, Ray S, Mishra A, Kalia VC (2015) Biodiesel industry waste: a potential source of bioenergy and biopolymers. Indian J Microbiol 55:1–7. doi: 10.1007/s12088-014-0509-1
14. Kumar P, Mehariya S, Ray S, Mishra A, Kalia VC (2015) Biotechnology in aid of biodiesel industry effluent (glycerol): biofuels and bioplastics. In: Microbial Factories (Ed. Kalia VC). Springer, New Delhi, pp 105–119. doi: 10.1007/978-81-322-2598-0
15. Kumar P, Ray S, Patel SKS, Lee JK, Kalia VC (2015) Bioconversion of crude glycerol to polyhydroxyalkanoate by Bacillus thuringiensis under non-limiting nitrogen conditions. Int J Biol Macromol 78:9–16. doi: 10.1016/j.ijbiomac.2015.03.046
16. Levine AC, Sparano A, Twigg FF, Numata K, Nomura CT (2015) Influence of cross-linking on the physical properties and cytotoxicity of polyhydroxyalkanoate (PHA) sccaffolds for tissue engineering. ACS Biomater Sci Eng 1:567−576. doi: 10.1021/acsbiomaterials.6b00279
17. Ludevese‐Pascual G, Laranja JLQ, Amar EC, Sorgeloos P, Bossier P, De Schryver P (2016) Poly‐beta‐hydroxybutyrate‐enriched Artemia sp. for giant tiger prawn Penaeus monodon larviculture. Aquaculture 23:422-429. doi: 10.1111/anu.12410
18. Martinez V, Dinjaski N, De Eugenio LI, De la Pena F, Prieto MA (2014) Cell system engineering to produce extracellular polyhydroxyalkanoate depolymerase with targeted applications. Int J Biol Macromol 71:28-33. doi: 10.1016/j.ijbiomac.2014.04.013
19. Mokhtarzadeh A (2016) Recent advances on biocompatible and biodegradable nanoparticles as gene carriers. Expert Opin Biol Ther 16: 771-785. doi: 10.1517/14712598.2016.1169269
20. 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: 1209-1221. doi: 10.1002/jctb.4685
21. O'Connor S, Szwej E, Nikodinovic-Runic J, O'Connor A, Byrne AT, Devocelle M, O'Donovan N, Gallagher WM, Babu R, Kenny ST, Zinn M (2013) The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate. Biomaterials 34:2710-2718. doi: 10.1016/j.biomaterials.2012.12.032
22. Parlane NA, Chen S, Jones GJ, Vordermeier HM, Wedlock DN, Rehm BH, Buddle BM (2016) Display of antigens on polyester inclusions lowers the antigen concentration required for a bovine tuberculosis skin test. Clin Vaccine Immunol 23:19-26. doi: 10.1128/CVI.00462-15
23. Parlane NA, Gupta SK, Rubio-Reyes P, Chen S, Gonzalez-Miro M, Wedlock DN, Rehm BH (2016) Self-assembled protein-coated polyhydroxyalkanoate beads: properties and biomedical applications. ACS Biomater Sci Eng doi: 10.1021/acsbiomaterials.6b00355
24. Patel SKS, Kumar P, Singh S, Lee JK, Kalia VC (2015) Integrative approach for hydrogen and polyhydroxybutyrate production. In Microbial factories: Waste treatment (Ed. Kalia VC). Springer, New Delhi, pp 73–85. doi: 10.1007/978-81-322-2598- 0_5
25. Patel SKS, Kumar P, Singh S, Lee JK, Kalia VC (2015) Integrative approach to produce hydrogen and polyhydroxybutyrate from biowaste using defined bacterial cultures. Bioresour Technol 176:136–141. doi: 10.1016/j.biortech.2014.11.029
26. Patel SKS, Lee JK, Kalia VC (2016) Integrative approach for producing hydrogen and polyhydroxyalkanoate from mixed wastes of biological origin. Indian J Microbiol 56:293-300. doi: 10.1007/s12088-016-0595-3
27. Rașoga O, Sima L, Chirițoiu M, Popescu-Pelin G, Fufă O, Grumezescu O, Socol M, Stănculescu A, Zgură I, Socol G (2017) Biocomposite coatings based on Poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/calcium phosphates obtained by MAPLE for bone tissue engineering. App Surf Sci doi: 10.1016/j.apsusc.2017.01.205
28. Raut S, Raut S, Sharma M, Srivastav C, Adhikari B, Sen SK (2015) Enhancing degradation of low density polyethylene films by Curvularia lunata SG1 using particle swarm optimization strategy. Indian J Microbiol 55: 258-268. doi: 10.1007/s12088-015-0522-z.
29. Ray S, Kalia VC (2016) Microbial cometabolism and polyhydroxyalkanoate co-polymers. Indian J Microbiol 57:39-47. doi: 10.1007/s12088-016-0622-4
30. Ray S, Kalia VC (2017) Co-metabolism of substrates by Bacillus thuringiensis regulates polyhydroxyalkanoate co-polymer composition. Bioresour Technol 224:743-747. doi: 10.1016/j.biortech.2016.11.089
31. Rodríguez-Contreras A, García Y, Manero J M, Rupérez E (2017) Antibacterial PHAs coating for titanium implants. European Polymer J doi: 10.1016/j.eurpolymj.2017.03.004
32. Sangsanoh P, Israsena N, Suwantong O, Supaphol P (2017) Effect of the surface topography and chemistry of poly(3-hydroxybutyrate) substrates on cellular behavior of the murine neuroblastoma Neuro2a cell line. Polym Bull doi:10.1007/s00289-017-1947-9
33. 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. doi: 10.1007/s10856-016-5776-4
34. Singh M, Kumar P, Ray S, Kalia VC (2015) Challenges and opportunities for the customizing polyhydroxyalkanoates. Indian J Microbiol 55:235–249. doi: 10.1007/s12088-015-0528-6
35. Singh M, Patel SKS, Kalia VC (2009) Bacillus subtilis as potential producer for polyhydroxyalkanoates. Microb Cell Fact 8:38. doi: 10.1186/1475-2859-8-38
36. Williams SF, Martin DP (2005) Applications of polyhydroxyalkanoates (PHA) in medicine and pharmacy. Biopolymers Online. doi: 10.1002/3527600035.bpol4004
37. Zhang J, Qian C, Shaowu L, Xiaoyun L, Yongxi Z, Ji-Song G, Jin-Chun C, Qiong W, Guo-Qiang C (2013) 3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer's disease via mitochondria protection mechanism. Biomater 34:7552-7562. doi: 10.1016/j.biomaterials.2013.06.043
About Author / Additional Info:
Researchers in Microbial Biotechnology and Genomics at CSIR-IGIB, Delhi.
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