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Doping and Incorporation of Hydroxyapatite in Development of PU-PLA Electrospun Osteogenic Membranes

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Abstract

Complete restoration of bones to treat oral and craniofacial skeletal disorders, presents a challenge for orthopedic and maxillofacial experts. In the present research hydroxyapatite (HA) the main constituent of bone, has been modified with various dopants to enhance the biological as well as mechanical properties of skeletal tissue. The doped bioactive HA powder has been incorporated in the polymeric matrix of polyurethane (PU) and poly l lactic acid (PLLA) to fabricate osteogenic membranes. Four different composites were fabricated with dopants such as Sr, Mg, SiO4, and CO3 and were named as PU-PLA-Sr-HA, PU-PLA-Mg-HA, PU-PLA-Si-HA and PU-PLA-C-HA. The prepared osteogenic membranes were characterized using FTIR, XRD and EDX analyses. In vitro characterization was done to evaluate cell proliferation and calcium deposition using the MC3T3 pre-osteoblast cell line on the membranes. The mechanical properties i.e. tensile strength was also evaluated with respect to dopant types and their concentration. FTIR, XRD and EDX spectral analyses confirm the various dopings in the prepared HA powder. PU-PLA-Sr-HA membranes exhibit porous fibers with uniformly distributed pores along the surface of fibers. The tensile strength of membranes containing doped HA was higher than the membrane without adding HA powder. The Young’s modulus of PU-PLA-Mg-HA and PU-PLA-Si-HA membranes was higher compared to the other samples. Lowest Young’s modulus value was observed in the PU-PLA-Sr-HA membrane. Cell viability assay displayed very high biocompatibility for all the prepared membranes, specifically PU-PLA-C-HA and PU-PLA-Sr-HA membranes showed higher cell proliferation. Moreover, the doped HA incorporated membranes showed increased deposition of calcium through the Alizarin Red assay. In conclusion the electrospun fibrous membranes with doped HA displayed improved osteogenic properties and hence can be an excellent candidate for bone and dental regenerative applications.

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References

  1. Fereshteh Z, Fathi M, Bagri A, Boccaccini AR (2016) Preparation and characterization of aligned porous PCL/zein scaffolds as drug delivery systems via improved unidirectional freeze-drying method. Mater Sci Eng C 68:613–622

    CAS  Google Scholar 

  2. Domalik-Pyzik P, Morawska-Chochół A, Chłopek J, Rajzer I, Wrona A, Menaszek E, Ambroziak M (2016) Polylactide/polycaprolactone asymmetric membranes for guided bone regeneration. e-Polymers 16(5):351–358

    CAS  Google Scholar 

  3. Rajzer I (2014) Fabrication of bioactive polycaprolactone/hydroxyapatite scaffolds with final bilayer nano-/micro-fibrous structures for tissue engineering application. J Mater Sci 49(16):5799–5807

    CAS  Google Scholar 

  4. Krishnan R, Sundarrajan S, Ramakrishna S (2013) Green processing of nanofibers for regenerative medicine. Macromol Mater Eng 298(10):1034–1058

    CAS  Google Scholar 

  5. Boccaccini AR, Blaker JJ (2005) Bioactive composite materials for tissue engineering scaffolds. Expert Rev Med Devices 2(3):303–317

    PubMed  CAS  Google Scholar 

  6. Sasaki M, Inoue M, Katada Y, Nishida Y, Taniguchi A, Hiromoto S, Taguchi T (2012) Preparation and biological evaluation of hydroxyapatite-coated nickel-free high-nitrogen stainless steel. Sci Technol Adv Mater 13(6):064213

    PubMed  PubMed Central  Google Scholar 

  7. Prakasam M, Locs J, Salma-Ancane K, Loca D, Largeteau A, Berzina-Cimdina L (2015) Fabrication, properties and applications of dense hydroxyapatite: a review. J Funct Biomater 6(4):1099–1140

    PubMed  PubMed Central  CAS  Google Scholar 

  8. Jaffe WL, Scott DF (1996) Total hip arthroplasty with hydroxyapatite-coated prostheses. J Bone Joint Surg Am 78(12):1918–1934

    PubMed  CAS  Google Scholar 

  9. Bi L, Jung S, Day D, Neidig K, Dusevich V, Eick D, Bonewald L (2012) Evaluation of bone regeneration, angiogenesis, and hydroxyapatite conversion in critical-sized rat calvarial defects implanted with bioactive glass scaffolds. J Biomed Mater Res Part A 100A(12):3267–3275

    CAS  Google Scholar 

  10. El-Ghannam A, Ducheyne P, Shapiro IM (1997) Porous bioactive glass and hydroxyapatite ceramic affect bone cell function in vitro along different time lines. J Biomed Mater Res 36(2):167–180

    PubMed  CAS  Google Scholar 

  11. Rezwan K, Chen Q, Blaker J, Boccaccini AR (2006) Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 27(18):3413–3431

    PubMed  CAS  Google Scholar 

  12. Kruse A, Jung R, Nicholls F, Zwahlen R, Hämmerle C, Weber F (2011) Bone regeneration in the presence of a synthetic hydroxyapatite/silica oxide-based and a xenogenic hydroxyapatite-based bone substitute material. Clin Oral Implant Res 22(5):506–511

    CAS  Google Scholar 

  13. Gibson I, Best S, Bonfield W (1999) Chemical characterization of silicon-substituted hydroxyapatite. J Biomed Mater Res Part A 44(4):422–428

    CAS  Google Scholar 

  14. Wei J, Jia J, Wu F, Wei S, Zhou H, Zhang H, Shin J-W, Liu C (2010) Hierarchically microporous/macroporous scaffold of magnesium–calcium phosphate for bone tissue regeneration. Biomaterials 31(6):1260–1269

    PubMed  CAS  Google Scholar 

  15. Wu F, Wei J, Guo H, Chen F, Hong H, Liu C (2008) Self-setting bioactive calcium–magnesium phosphate cement with high strength and degradability for bone regeneration. Acta Biomater 4(6):1873–1884

    PubMed  CAS  Google Scholar 

  16. Maeda H, Kasuga T, Hench LL (2006) Preparation of poly (L-lactic acid)-polysiloxane-calcium carbonate hybrid membranes for guided bone regeneration. Biomaterials 27(8):1216–1222

    PubMed  CAS  Google Scholar 

  17. Barrère F, van Blitterswijk CA, de Groot K (2006) Bone regeneration: molecular and cellular interactions with calcium phosphate ceramics. Int J Nanomed 1(3):317–332

    Google Scholar 

  18. O’donnell M, Hill R (2010) Influence of strontium and the importance of glass chemistry and structure when designing bioactive glasses for bone regeneration. Acta Biomater 6(7):2382–2385

    PubMed  Google Scholar 

  19. Wong C, Lu W, Chan W, Cheung K, Luk K, Lu D, Rabie A, Deng L, Leong J (2004) In vivo cancellous bone remodeling on a strontium-containing hydroxyapatite (sr-HA) bioactive cement. J Biomed Mater Res Part A 68(3):513–521

    CAS  Google Scholar 

  20. Veresov A, Putlyaev V, Tret’yakov YD (2004) Chemistry of inorganic biomaterials based on calcium phosphates. Ross Khim Zh 48(4):52–64

    CAS  Google Scholar 

  21. Carlisle EM (1970) Silicon: a possible factor in bone calcification. Science 167(3916):279–280

    PubMed  CAS  Google Scholar 

  22. Blake G, Zivanovic M, McEwan A, Ackery D (1986) Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate. Eur J Nucl Med Mol Imaging 12(9):447–454

    CAS  Google Scholar 

  23. Ammann P, Shen V, Robin B, Mauras Y, Bonjour JP, Rizzoli R (2004) Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res 19(12):2012–2020

    PubMed  CAS  Google Scholar 

  24. Grynpas M, Hamilton E, Cheung R, Tsouderos Y, Deloffre P, Hott M, Marie P (1996) Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect. Bone 18(3):253–259

    PubMed  CAS  Google Scholar 

  25. Marie PJ, Hott M, Modrowski D, De Pollak C, Guillemain J, Deloffre P, Tsouderos Y (2005) An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 20(6):1065–1074

    Google Scholar 

  26. Li Y, Li Q, Zhu S, Luo E, Li J, Feng G, Liao Y, Hu J (2010) The effect of strontium-substituted hydroxyapatite coating on implant fixation in ovariectomized rats. Biomaterials 31(34):9006–9014

    PubMed  CAS  Google Scholar 

  27. Fu D-l, Jiang Q-h, He F-m, Yang G-l, Liu L (2012) Fluorescence microscopic analysis of bone osseointegration of strontium-substituted hydroxyapatite implants. J Zhejiang Univ Sci B 13(5):364–371

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Zhu K, Yanagisawa K, Shimanouchi R, Onda A, Kajiyoshi K (2006) Preferential occupancy of metal ions in the hydroxyapatite solid solutions synthesized by hydrothermal method. J Eur Ceram Soc 26(4):509–513

    CAS  Google Scholar 

  29. Bigi A, Boanini E, Capuccini C, Gazzano M (2007) Strontium-substituted hydroxyapatite nanocrystals. Inorg Chim Acta 360(3):1009–1016

    CAS  Google Scholar 

  30. Klein G, De Groot K, Driessen A, Van der Lubbe H (1986) A comparative study of different β-whiUockite ceramics in rabbit cortical bone with regard to their biodegradation behaviour. Biomaterials 7(2):144–146

    PubMed  CAS  Google Scholar 

  31. Dhert W, Klein C, Jansen J, Van der Velde E, Vriesde R, Rozing P, De Groot K (1993) A histological and histomorphometrical investigation of fluorapatite, magnesiumwhitlockite, and hydroxylapatite plasma-sprayed coatings in goats. J Biomed Mater Res Part A 27(1):127–138

    CAS  Google Scholar 

  32. Webster TJ, Ergun C, Doremus RH, Bizios R (2002) Hydroxylapatite with substituted magnesium, zinc, cadmium, and yttrium. II. Mechanisms of osteoblast adhesion. J Biomed Mater Res 59(2):312–317

    PubMed  CAS  Google Scholar 

  33. Webster TJ, Massa-Schlueter EA, Smith JL, Slamovich EB (2004) Osteoblast response to hydroxyapatite doped with divalent and trivalent cations. Biomaterials 25(11):2111–2121

    PubMed  CAS  Google Scholar 

  34. Pham QP, Sharma U, Mikos AG (2006) Electrospun poly (ε-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. Biomacromol 7(10):2796–2805

    CAS  Google Scholar 

  35. Milner KR, Siedlecki CA (2007) Submicron poly (L-lactic acid) pillars affect fibroblast adhesion and proliferation. J Biomed Mater Res Part A 82(1):80–91

    Google Scholar 

  36. Stevens MM, George JH (2005) Exploring and engineering the cell surface interface. Science 310(5751):1135–1138

    PubMed  CAS  Google Scholar 

  37. Bettinger CJ, Langer R, Borenstein JT (2009) Engineering substrate topography at the micro- and nanoscale to control cell function. Angew Chem Int Ed 48(30):5406–5415

    CAS  Google Scholar 

  38. Maheshwari G, Brown G, Lauffenburger DA, Wells A, Griffith LG (2000) Cell adhesion and motility depend on nanoscale RGD clustering. J Cell Sci 113(10):1677–1686

    PubMed  CAS  Google Scholar 

  39. Khil MS, Cha DI, Kim HY, Kim IS, Bhattarai N (2003) Electrospun nanofibrous polyurethane membrane as wound dressing. J Biomed Mater Res B 67(2):675–679

    Google Scholar 

  40. Ghosal K, Thomas S, Kalarikkal N, Gnanamani A (2014) Collagen coated electrospun polycaprolactone (PCL) with titanium dioxide (TiO2) from an environmentally benign solvent: preliminary physico-chemical studies for skin substitute. J Polym Res 21(5):410

    Google Scholar 

  41. Ghosal K, Manakhov A, Zajíčková L, Thomas S (2017) Structural and surface compatibility study of modified electrospun poly (ε-caprolactone)(pcl) composites for skin tissue engineering. AAPS PharmSciTech 18(1):72–81

    PubMed  CAS  Google Scholar 

  42. Xu C, Inai R, Kotaki M, Ramakrishna S (2004) Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering. Biomaterials 25(5):877–886

    PubMed  CAS  Google Scholar 

  43. Wang G, Hu X, Lin W, Dong C, Wu H (2011) Electrospun PLGA–silk fibroin–collagen nanofibrous scaffolds for nerve tissue engineering. Vitro Cell Dev Biol Anim 47(3):234–240

    CAS  Google Scholar 

  44. Sun C, Jin X, Holzwarth JM, Liu X, Hu J, Gupte MJ, Zhao Y, Ma PX (2012) Development of channeled nanofibrous scaffolds for oriented tissue engineering. Macromol Biosci 12(6):761–769

    PubMed  PubMed Central  CAS  Google Scholar 

  45. He X, Fu W, Feng B, Wang H, Liu Z, Yin M, Wang W, Zheng J (2013) Electrospun collagen/poly (L-lactic acid-co-ε-caprolactone) hybrid nanofibrous membranes combining with sandwich construction model for cartilage tissue engineering. J Nanosci Nanotechnol 13(6):3818–3825

    PubMed  CAS  Google Scholar 

  46. Yoshimoto H, Shin Y, Terai H, Vacanti J (2003) A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials 24(12):2077–2082

    PubMed  CAS  Google Scholar 

  47. Rnjak-Kovacina J, Weiss AS (2011) Increasing the pore size of electrospun scaffolds. Tissue Eng Part B 17(5):365–372

    CAS  Google Scholar 

  48. Gigliobianco G, Chong CK, MacNeil S (2015) Simple surface coating of electrospun poly-L-lactic acid scaffolds to induce angiogenesis. J Biomater Appl 30(1):50–60

    PubMed  CAS  Google Scholar 

  49. Barry AL, Craig WA, Nadler H, Reller LB, Sanders CC, Swenson JM: Methods for determining bactericidal activity of antimicrobial agents: approved guideline. NCCLS Document M26-A 1999, 19(18)

  50. Landi E, Logroscino G, Proietti L, Tampieri A, Sandri M, Sprio S (2008) Biomimetic Mg-substituted hydroxyapatite: from synthesis to in vivo behaviour. J Mater Sci 19(1):239–247

    CAS  Google Scholar 

  51. Kulanthaivel S, Mishra U, Agarwal T, Giri S, Pal K, Pramanik K, Banerjee I (2015) Improving the osteogenic and angiogenic properties of synthetic hydroxyapatite by dual doping of bivalent cobalt and magnesium ion. Ceram Int 41(9):11323–11333

    CAS  Google Scholar 

  52. Bang LT, Ramesh S, Purbolaksono J, Ching YC, Long BD, Chandran H, Ramesh S, Othman R (2015) Effects of silicate and carbonate substitution on the properties of hydroxyapatite prepared by aqueous co-precipitation method. Mater Des 87:788–796

    CAS  Google Scholar 

  53. Fallahiarezoudar E, Ahmadipourroudposht M, Idris A, Yusof NM (2017) Optimization and development of Maghemite (γ-Fe2O3) filled poly-L-lactic acid (PLLA)/thermoplastic polyurethane (TPU) electrospun nanofibers using Taguchi orthogonal array for tissue engineering heart valve. Mater Sci Eng C 76:616–627

    CAS  Google Scholar 

  54. Cox SC, Jamshidi P, Grover LM, Mallick KK (2014) Preparation and characterisation of nanophase Sr, Mg, and Zn substituted hydroxyapatite by aqueous precipitation. Mater Sci Eng, C 35:106–114

    CAS  Google Scholar 

  55. Xu Y, An L, Chen L, Xu H, Zeng D, Wang G (2018) Controlled hydrothermal synthesis of strontium-substituted hydroxyapatite nanorods and their application as a drug carrier for proteins. Adv Powder Technol 29(4):1042–1048

    CAS  Google Scholar 

  56. Khandelwal H, Prakash S (2016) Synthesis and characterization of hydroxyapatite powder by eggshell. J Miner Mater Charact Eng 4(02):119

    CAS  Google Scholar 

  57. Tetteh G, Khan AS, Delaine-Smith RM, Reilly GC, Rehman IU (2014) Electrospun polyurethane/hydroxyapatite bioactive Scaffolds for bone tissue engineering: the role of solvent and hydroxyapatite particles. J Mech Behav Biomed Mater 39:95–110

    PubMed  CAS  Google Scholar 

  58. Casper CL, Stephens JS, Tassi NG, Chase DB, Rabolt JF (2004) Controlling surface morphology of electrospun polystyrene fibers: effect of humidity and molecular weight in the electrospinning process. Macromolecules 37(2):573–578

    CAS  Google Scholar 

  59. Megelski S, Stephens JS, Chase DB, Rabolt JF (2002) Micro- and nanostructured surface morphology on electrospun polymer fibers. Macromolecules 35(22):8456–8466

    CAS  Google Scholar 

  60. Celebioglu A, Uyar T (2011) Electrospun porous cellulose acetate fibers from volatile solvent mixture. Mater Lett 65(14):2291–2294

    CAS  Google Scholar 

  61. Cooper CJ, Mohanty AK, Misra M (2018) Electrospinning process and structure relationship of biobased poly(butylene succinate) for nanoporous fibers. ACS Omega 3(5):5547–5557

    PubMed  PubMed Central  CAS  Google Scholar 

  62. Zhang H-P, Lu X, Leng Y, Fang L, Qu S, Feng B, Weng J, Wang J (2009) Molecular dynamics simulations on the interaction between polymers and hydroxyapatite with and without coupling agents. Acta Biomater 5(4):1169–1181

    PubMed  CAS  Google Scholar 

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Acknowledgement

Authors would like to acknowledge the support of the research funds from Higher Education Comission Pakistan under NRPU project # 4078. We would like to thank Dr Farasat Iqbal for support in elemental analysis.

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Correspondence to Faiza Sharif.

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Mustafa, W., Azhar, U., Tabassum, S. et al. Doping and Incorporation of Hydroxyapatite in Development of PU-PLA Electrospun Osteogenic Membranes. J Polym Environ 28, 2988–3002 (2020). https://doi.org/10.1007/s10924-020-01764-1

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