Poly(3-hydroxybutyrate): Promising biomaterial for bone tissue engineering

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Abstract

Poly(3-hydroxybutyrate) is a natural polymer, produced by different bacteria, with good biocompatibility and biodegradability. Cardiovascular patches, scaffolds in tissue engineering and drug carriers are some of the possible biomedical applications of poly(3-hydroxybutyrate). In the past decade, many researchers examined the different physico-chemical modifications of poly(3-hydroxybutyrate) in order to improve its properties for use in the field of bone tissue engineering. Poly(3-hydroxybutyrate) composites with hydroxyapatite and bioglass are intensively tested with animal and human osteoblasts in vitro to provide information about their biocompatibility, biodegradability and osteoinductivity. Good bone regeneration was proven when poly(3-hydroxy-butyrate) patches were implanted in vivo in bone tissue of cats, minipigs and rats. This review summarizes the recent reports of in vitro and in vivo studies of pure poly(3-hydroxy-butyrate) and poly(3-hydroxybutyrate) composites with the emphasis on their bioactivity and biocompatibility with bone cells.

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  • 1. H. Tian Z. Tang X. Zhuang X. Chen and X. Jing Biodegradable synthetic polymers: Preparation functionalization and biomedical application Prog. Polym. Sci. 37 (2012) 237−280; https://doi.org/10.1016/j.progpolymsci.2011.06.004

  • 2. D. B. Hazer E. Kiliçay and B. Hazer Poly(3-hydroxyalkanoate)s: Diversification and biomedical applications A state of art review Mater. Sci. Eng. C 32 (2012) 637−647; https://doi.org/10.1016/j.msec.2012.01.021

  • 3. M. Goonoo A. Bhaw-Luximon P. Passanha S. R. Esteves and D. Jhurry Third generation poly(hydroxyacid) composite scaffolds for tissue reengineering J. Biomed. Mater. Res. B Appl. Biomater. 105B (2017) 1667−1684; https://doi.org/10.1002/jbm.b.33674

  • 4. A. R. Amini C. T. Laurencin and S. P. Nukavarapu Bone tissue engineering: recent advances and challenges Crit. Rev. Biomed. Eng. 40 (2012) 363−408.

  • 5. S. Bose M. Roy and A. Bandyopadhyay Recent advances in bone tissue engineering scaffolds Trends Biotechnol. 30 (2012) 546−554; https://doi.org/10.1016/j.tibtech.2012.07.005

  • 6. L. Wu L. Wang X. Wang and K. Xu Synthesis characterization and biocompatibility of novel bio-degradable star block copolymers based on poly[(R)-3-hydroxybutyrate] and poly(ε-caprolactone) Acta Biomater. 6 (2010) 1079−1089; https://doi.org/10.1016/j.actbio.2009.08.014

  • 7. E. Masaeli M. Morshed P. Rasekhian S. Karbasi K. Karbalaie F. Karamali D. Abedi S. Razavi A. Jafarian-Dehkordi M. H. Nasr-Esfahani and H. Baharvand Does the tissue engineering architecture of Poly(3-hydroxybutyrate) scaffolds affect cell-material interactions? J. Biomed. Mater. Res. A 100A (2012) 1907−1918; https://doi.org/10.1002/jbm.a.34131

  • 8. M. M. Reddy S. Vivekanandhan M. Misra S. K. Bhatia and A. K. Mohanty Biobased plastics and bionanocomposites: Current status and future opportunities Prog. Polym. Sci. 38 (2013) 1653−1689; https://doi.org/10.1016/j.progpolymsci.2013.05.006

  • 9. C. Peña T. Castillo A. Garcia M. Millan and D. Segura Biotechnological strategies to improve production of microbial poly(3-hydroxybutyrate): a review of recent research work Microbial Biotechnol. 7 (2014) 278−293; https://doi.org/10.1111/1751-7915.12129

  • 10. S. Centeno-Leija G. Huerta-Beristain M. Giles-Gomez F. Bolivar G. Gosset and A. Martinez Improving poly-3-hydroxybutyrate production in Escherichia coli by combining the increase in the NADPH pool and acetyl-CoA availability Antonie van Leeuwenhoek 105 (2014) 687−696; https://doi.org/10.1007/s10482-014-0124-5

  • 11. A. M. Hayati S. M. Hosseinalipour H. R. Rezaie and M. A. Shokrgozar Characterization of poly(3-hydroxybutyrate)/nano-hydroxyapatite composite scaffolds fabricated without the use of organic solvents for bone tissue engineering applications Mater. Sci. Eng. C 32 (2012) 416−422; https://doi.org/10.1016/j.msec.2011.11.013

  • 12. B. S. Kushwah A. V. S. Kushwah and V. Singh Towards understanding polyhydroxyalkanoates and their use J. Polym. Res. 23 (2016) 153−166; https://doi.org/10.1007/s10965-016-0988-3

  • 13. R. W. Lenz and R. H. Marchessault Bacterial polyesters: Biosynthesis biodegradable plastics and biotechnology Biomacromolecules 6 (2005) 1−8; https://doi.org/10.1021/bm049700c

  • 14. Y. Zhao B. Zou Z. Shi Q. Wu and G. Q. Chen 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 (2007) 3063−3073; https://doi.org/10.1016/j.biomaterials.2007.03.003

  • 15. S. Cheng G. Q. Chen M. Leski B. Zou Y. Wang and Q. Wu The effect of DL-β-hydroxybutyric acid on cell death and proliferation Biomaterials 27 (2006) 3758−3765; https://doi.org/10.1016/j.biomaterials.2006.02.046

  • 16. C. J. Brigham and A. J. Sinskey Applications of polyhydroxyalkanoates in the medical industry Int. J. Biotechnol. Wellness Ind. (IJBWI) 1 (2012) 53−60

  • 17. E. I. Shishatskaya and T. G. Volova A comparative investigation of biodegradable polyhydroxyalkanoate films as matrices for in vitro cell cultures J. Mater. Sci. Mater. Med. 15 (2004) 915−923; https://doi.org/10.1023/B:JMSM.0000036280.98763.c1

  • 18. S. W. Hong H. W. Hsu and M. T. Ye Thermal properties and applications of low molecular weight polyhydroxybutyrate J. Therm. Anal. Calorim. 111 (2013) 1243−1250; https://doi.org/10.1007/s10973-012-2503-3

  • 19. I. Manavitehrani A. Fathi H. Badr S. Daly A. N. Shirazi and F. Dehghani Biomedical applications of biodegradable polyesters Polymers 8 (2016) Article ID 20 (32 pages); https://doi.org/10.3390/polym8010020

  • 20. R. Y. Basha S. Kumar and M. Doble Design of biocomposite materials for bone tissue regeneration Mater. Sci. Eng. C 57 (2015) 452−463; https://doi.org/10.1016/j.msec.2015.07.016

  • 21. S. H. Lee and H. Shin Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering Adv. Drug Deliv. Rev. 59 (2007) 339−359; https://doi.org/10.1016/j.addr.2007.03.016

  • 22. D. W. Hutmacher Scaffolds in tissue engineering bone and cartilage Biomaterials 21 (2000) 2529−2543; https://doi.org/10.1016/S0142-9612(00)00121-6

  • 23. P. P. Lopes M. P. Garcia M. H. Fernandes and M. H. V. Fernandes Acrylic formulations containing bioactive and biodegradable filters to be used as bone cements: Properties and biocompatibility assessment Mater. Sci. Eng. C 33 (2013) 1289−1299; https://doi.org/10.1016/j.msec.2012.12.028

  • 24. M. Sadat-Shojai M. T. Khorasani A. Jamshidi and S. Irani Nano-hydroxyapatite reinforced polyhydroxybutyrate composites: A comprehensive study on the structural and in vivo biological properties Mater. Sci. Eng. C 33 (2013) 2776−2787; https://doi.org/10.1016/j.msec.2013.02.041

  • 25. Y. Zhang L. Hao M. M. Savalani R. A. Harris L. Di Silvio and K. E. Tanner In vitro biocompatibility of hydroxyapatite-reinforced polymeric composites manufactured by selective laser sintering J. Biomed. Mater. Res. A 91A (2009) 1018−1027; https://doi.org/10.1002/jbm.a.32298

  • 26. H. Zhou and J. Lee Nanoscale hydroxyapatite particles for bone tissue engineering Acta Biomater. 7 (2011) 2769−2781; https://doi.org/10.1016/j.actbio.2011.03.019

  • 27. J. Michel M. Penna J. Kochen and H. Cheung Recent advances in hydroxyapatite scaffolds containing mesenchymal stem cells Stem Cell. Int. 2015 (2015) Article ID 305217 (13 pages); https://doi.org/10.1155/2015/305217

  • 28. Y. W. Wang Q. Wu J. Chen and G. Q. Chen Evaluation of three-dimensional scaffolds made of blends of hydroxyapatite and poly(3-hydroxybutyrate-co-3-hydroxyhexynoate) for bone reconstruction Biomaterials 26 (2005) 899−904; https://doi.org/10.1016/j.biomaterials.2004.03.035

  • 29. E. I. Shishatskaya I. A. Khlusov and T. G. Volova A hybrid PHB-hydroxyapatite composite for biomedical application: production in vitro and in vivo investigation J. Biomater. Sci. Polym. Ed. 17 (2006) 481−498.

  • 30. J. Ramier D. Grande T. Bouderlique O. Stoilova N. Manolova I. Rashkov V. Langlois P. Albanese and E. Renard From design of bio-based biocomposite electrospun scaffolds to osteogenic differentiation of human mesenchymal stromal cells J. Mater. Sci. Mater. Med. 25 (2014) 1563−1575; https://doi.org/10.1007/s10856-014-5174-8

  • 31. A. Saadat A.A. Behnamghader S. Karbasi D. Abedi M. Soleimani and A. Shafiee Comparison of acellular and cellular bioactivity of poly 3-hydroxybutyrate/hydroxyapatite nanocomposite and poly 3-hydroxybutyrate scaffolds Biotechnol. Bioprocess Eng. 18 (2013) 587−593; https://doi.org/10.1007/s12257-012-0744-4

  • 32. Z. Chen Y. Song J. Zhang W. Liu J. Cui H. Li and F. Chen Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering Mater. Sci. Eng. C 72 (2017) 341−351; https://doi.org/10.1016/j.msec.2016.11.070

  • 33. M. Sadat-Shojai Electrospun polyhydroxybutyrate/hydroxyapatite nanohybrids: microstructure and bone cell response J. Mater. Sci. Technol. 32 (2016) 1013−1020; https://doi.org/10.1016/j.jmst.2016.07.007

  • 34. B. Pourmollaabbassi S. Karbasi and B. Hashemibeni Evaluate the growth and adhesion of osteo-blast cells on nanocomposite scaffold of hydroxyapatite/titania coated with poly hydroxybutyrate Adv. Biomed. Res. 5 (2016) Article ID 156 (11 pages); https://doi.org/10.4103/2277-9175.188486

  • 35. H. Hajiali M. Hosseinalipour S. Karbasi and M. A. Shokrgozar The influence of bioglass nano-particles on the biodegradation and biocompatibility of poly(3-hydroxybutyrate) scaffolds Int. J. Artif. Organs 35 (2012) 1015−1024; https://doi.org/10.5301/ijao.5000119

  • 36. S. K. Misra T. I. Ansari S. P. Valappil D. Mohn S. E. Philip W. J. Stark I. Roy J. C. Knowles V. Salih and A. R. Boccaccini Poly(3-hydroxybutyrate) multifunctional composite scaffolds for tissue engineering applications Biomaterials 31 (2010) 2806−2815; https://doi.org/10.1016/j.biomaterials.2009.12.045

  • 37. M. Meischel J. Eichler E. Martinelli U. Karr J. Weigel G. Schmöller E. K. Tschegg S. Fischerauer A. M. Weinberg and S. E. Stanzl-Tschegg Adhesive strength of bone-implant interfaces and in-vivo degradation of PHB composites for load-bearing applications J. Mech. Behav. Biomed. Mater. 53 (2016) 104−118; https://doi.org/10.1016/j.jmbbm.2015.08.004

  • 38. M. Franceschini A. Di Matteo H. Bösebeck H. Büchner and S. Vogt Treatment of a chronic recurrent fistulized tibial osteomyelitis: administration of a novel antibiotic-loaded bone substitute combined with a pedicular muscle flap sealing Eur. J. Orthop. Surg. Traumatol. 22 (2012) 245−249; https://doi.org/10.1007/s00590-012-0956-5

  • 39. L. Medvecky Microstructure and properties of polyhydroxybutyrate-chitosan-nanohydroxyapatite composite scaffolds Sci. World J. 2012 (2012) Article ID 537973 (8 pages); https://doi.org/10.1100/2012/537973

  • 40. H. Y. Tai E. Fu L.-P. Cheng and T.-M. Don Fabrication of asymmetric membranes from polyhydroxybutyrate and biphasic calcium phosphate/chitosan for guided bone regeneration J. Polym. Res. 21 (2014) Article ID 421 (12 pages); https://doi.org/10.1007/s10965-014-0421-8

  • 41. M. Giretova L. Medvecky R. Stulajterova T. Sopcak J. Briancin and M. Tatarkova Effect of enzymatic degradation of chitosan in polyhydroxybutyrate/chitosan/calcium phosphate composites on in vitro osteoblast response J. Mater. Sci. Mater. Med. 27 (2016) Article ID 181; https://doi.org/10.1007/s10856-016-5801-7

  • 42. Y. Ding Q. Yao W. Li D. W. Schubert A. R. Boccaccini and J. A. Roether The evaluation of physical properties and in vitro cell behavior of PHB/PCL/sol-gel derived silica hybrid scaffolds and PHB/PCL/fumed silica composite scaffolds Colloids Surf. B Biointerfaces 136 (2015) 93−98; https://doi.org/10.1016/j.colsurfb.2015.08.023

  • 43. Y. Ding W. Li T. Müller D. W. Schubert A. R. Boccaccini Q. Yao and J. A. Roether Electrospun polyhydroxybutyrate/poly(ε-caprolactone)/58S sol−gel bioactive glass hybrid scaffolds with highly improved osteogenic potential for bone tissue engineering Appl. Mater. Interfaces 8 (2016) 17098−17108; https://doi.org/10.1021/acsami.6b03997

  • 44. C. Zhijiang X. Yi Y. Haizheng J. Jia and Y. Liu Poly(hydroxybutyrate)/cellulose acetate blend nano-fiber scaffolds: Preparation characterization and cytocompatibility Mater. Sci. Eng. C 58 (2016) 757−767; https://doi.org/10.1016/j.msec.2015.09.048

  • 45. A. Venault A. Subarja and Y. Chang Zwitterionic polyhydroxybutyrate electrospun fibrous membranes with a compromise of bioinert control and tissue-cell growth Langmuir 33 (2017) 2460−2471; https://doi.org/10.1021/asc.langmuir.6b04683

  • 46. N. Goonoo A. Bhaw-Luximon P. Passanha S. Esteves H. Schönherr and D. Jhurry Biomineralization potential and cellular response of PHB and PHBV blends with natural anionic polysaccharides Mater. Sci. Eng. C 76 (2017) 13−24; https://doi.org/10.1016/j.msec2017.02.156

  • 47. H. Li H. Pan C. Ning G. Tan J. Liao and G. Ni Magnesium with micro-arc oxidation coating and polymeric membrane: an in vitro study on microenvironment J. Mater. Sci. Mater. Med. 26 (2015) Article ID 147; https://doi.org/10.1007/s10856-015-5428-0

  • 48. Y. W. Wang Q. Wu and G. Q. Chen Attachment proliferation and differentiation of osteoblasts on random biopolyester poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds Biomaterials 25 (2004) 669−675; https://doi.org/10.1016/S0142-9612(03)00561-1

  • 49. M. Sadat-Shojai M. T. Khorasani and A. Jamshidi A new strategy for fabrication of bone scaffolds using electrospun nano-Hap/PHB fibers and protein hydrogels Chem. Eng. J. 289 (2016) 38−47; https://doi.org/10.1016/j.cej.2015.12.079

  • 50. S. W. Peng X. Y. Guo G. G. Shang J. Li X. Y. Xu M. L. You P. Li and G. Q. Chen An assessment of the risk of carcinogenicity associated with polyhydroxyalkanoates through an analysis of DNA aneuploid and telomerase activity Biomaterials 32 (2011) 2546−2555; https://doi.org/10.1016/j.biomaterials.2010.12.051

  • 51. A. Q. Ali T. P. Kannan A. Ahmad and Ab. R. Samsudin In vitro genotoxicity tests for polyhydroxy-butyrate − A synthetic biomaterial Toxicol. in Vitro 22 (2008) 57−67; https://doi.org/10.1016/j.tiv.2007.08.001

  • 52. Y. Wang X. L. Jiang S. W. Peng X. Y. Guo G. G. Shang J. C. Chen Q. Wu and G. Q. Chen Induced apoptosis of osteoblasts proliferating on polyhydroxyalkanoates Biomaterials 34 (2013) 3737−3746; https://doi.org/10.1016/j.biomaterials.2013.01.088

  • 53. C. Rentsch B. Rentsch A. Breier A. Hofmann S. Manthey D. Scharnweber and H. Zwipp Evaluation of the osteogenic potential and vascularization of 3D poly(3)hydroxybutyrate scaffolds subcutaneously implanted in nude rats J. Biomed. Mater. Res. A 92A (2010) 185−195; https://doi.org/10.1002/jbm.a.32314

  • 54. Z. Karahaliloğlu B. Ercan E. N. Taylor S. Chung E. B. Denkbas and T. J. Webster Antibacterial nanostructured polyhydroxybutyrate membranes for guided bone regeneration J. Biomed. Nanotechnol. 11 (2015) 2253−2263; https://doi.org/10.1166/jbn.2015.2106

  • 55. I. Rozila P. Azari S. Munirah W. K. Z. W. Safwani S. N. Gan A. G. N. Azurah J. Jahendran B. Pingguan-Murphy and K. H. Chua Differential osteogenic potential of human adipose-derived stem cells co-cultured with human osteoblasts on polymeric microfiber scaffolds J. Biomed. Mater. Res. A 104A (2016) 377−387; https://doi.org/10.1002/jbm.a.35573

  • 56. P. Slepička I. Michaljaničová S. Rimpelová and V. Švorčík Surface roughness in action – Cells in opposition Mater. Sci. Eng. C 76 (2017) 818−826; https://doi.org/10.1016/j.msec.2017.03.061

  • 57. H. E. Bernd C. Kunze T. Freier K. Sternberg S. Kramer D. Behrend F. Prall M. Donat and B. Kramp Poly(3-hydroxybutyrate) (PHB) patches for covering anterior skull base defects - an animal study with minipigs Acta Otolaryngol. 129 (2009) 1010−1017; https://doi.org/10.1080/00016480802552493

  • 58. T. Gredes T. Gedrange C. Hinüber M. Gelinsky and C. Kunert-Keil Histological and molecular-biological analyses of poly(3-hydroxybutyrate) (PHB) patches for enhancement of bone regeneration Ann. Anat. 199 (2015) 36−42; https://doi.org/10.1016/j.aanat.2014.04.003

  • 59. E. G. L. Alves C. M. F. Rezende R. Serakides M. M. Pereira and I. R. Rosado Orthopedic implant of a polyhydroxybutyrate (PHB) and hydroxyapatite composite in cats J. Feline Med. Surg. 13 (2011) 546-552; https://doi.org/10.1016/j.jfms.2011.03.002

  • 60. A. Celarek T. Kraus E. K. Tschegg S. F. Fischerauer S. Stanzl-Tschegg P. J. Uggowitzer and A. M. Weinberg PHB crystalline and amorphous magnesium alloys: Promising candidates for bioresorbable osteosynthesis implants? Mater. Sci. Eng. C 32 (2012) 1503−1510; https://doi.org/10.1016/j.msec.2012.04.032

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