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Physicochemical characterisation of novel ultra-thin biodegradable scaffolds for peripheral nerve repair

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Abstract

In this study, the physicochemical properties of microporous poly (ε-caprolactone) (PCL) films and a composite material made of PCL and polylactic acid (PLA) blend were tested. Fabricated by solvent casting using dichloromethane, these ultra-thin films (60 ± 5 μm in thickness) have a novel double-sided surface topography, i.e. a porous surface with pores 1–10 μm in diameter and a relatively smooth surface with nano-scaled texture. Porous surfaces were found to be associated with increased protein adsorption and the treatment of these polyester scaffolds with NaOH rendered them more hydrophilic. Differential Scanning Calorimetry (DSC) showed that the incorporation of PLA reduced the crystallinity of the original homopolymer. Chemical changes were investigated by means of Fourier Transform Infrared Spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). Average surface roughness (Ra), hydrophilicity/hydrophobicity and mechanical properties of these materials were also assessed for the suitability of these materials as nerve conduits.

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References

  1. A.B. Dagum, Peripheral nerve regeneration, repair, and grafting. J. Hand Ther. 11, 111 (1998)

    PubMed  CAS  Google Scholar 

  2. P.N. Mohanna, R.C. Young, M. Wiberg, G. Terenghi, A composite poly-hydroxybutyrate-glial growth factor conduit for long nerve gap repairs. J. Anat. 203, 553 (2003). doi:10.1046/j.1469-7580.2003.00243.x

    Article  PubMed  CAS  Google Scholar 

  3. S.E. Mackinnon, A.L. Dellon, in Surgery of the Peripheral Nerve. Nerve Repair and Nerve Grafting (Thieme Medical Publishers, New York, 1988), pp. 89–129

  4. M.F. Meek, W.F.A. Den Dunnen, J.M. Schakenraad, P.H. Robinson, Evaluation of functional nerve recovery after reconstruction with a poly (DL-Lactide-ε-Caprolactone) nerve guide, filled with modified denatured muscle tissue. Microsurgery 17, 555 (1996). doi:10.1002/(SICI)1098-2752(1996)17:10<555::AID-MICR5>3.0.CO;2-P

    Article  PubMed  CAS  Google Scholar 

  5. R.D. Fields, J.M. Le Beau, F.M. Longo, M.H. Ellisman, Nerve regeneration through artificial tubular implants. Prog. Neurobiol. 33, 87 (1989). doi:10.1016/0301-0082(89)90036-1

    Article  PubMed  CAS  Google Scholar 

  6. C.E. Schmidt, J.B. Leach, Neural tissue engineering: strategies for repair and regeneration. Annu. Rev. Biomed. Eng. 5, 293 (2003). doi:10.1146/annurev.bioeng.5.011303.120731

    Article  PubMed  CAS  Google Scholar 

  7. R.S. Bezwada, D.D. Jamiolkowski, I.Y. Lee, V. Agarwal, J. Persivale, S. Trenka-Benthin, M. Erneta, J. Suryadevara, A. Yang, S. Liu, Monocryl® suture, a new ultra-pliable absorbable monofilament suture. Biomaterials 16, 1141 (1995). doi:10.1016/0142-9612(95)93577-Z

    Article  PubMed  CAS  Google Scholar 

  8. P.D. Darney, S.E. Monroe, C.M. Klaisle, A. Alvarado, Clinical evaluation of the Capronor contraceptive implant: preliminary report. Am. J. Obstet. Gynecol. 160, 1292 (1989)

    PubMed  CAS  Google Scholar 

  9. S. Dumitriu, Polymeric Biomaterials, 2nd edn. rev. (Marcel Dekker Inc., New York, 2001), pp. 95–97, 107–109, 402, 403

  10. S.C. Woodward, P.S. Brewer, F. Moatamed, A. Schindler, C.G. Pitt, The intracellular degradation of poly (ε-caprolactone). J. Biomed. Mater. Res. 19, 437 (1985). doi:10.1002/jbm.820190408

    Article  PubMed  CAS  Google Scholar 

  11. H. Kweon, M.K. Yoo, I.K. Park, T.H. Kim, H.C. Lee, H.S. Lee, J.S. Oh, T. Akaike, C.S. Cho, A novel degradable polycaprolactone networks for tissue engineering. Biomaterials 24, 801 (2003). doi:10.1016/S0142-9612(02)00370-8

    Article  PubMed  CAS  Google Scholar 

  12. G. Chouzouri, M. Xanthos, In vitro bioactivity and degradation of polycaprolactone composites containing silicate fillers. Acta Biomater. 3, 745 (2007). doi:10.1016/j.actbio.2007.01.005

    Article  PubMed  CAS  Google Scholar 

  13. P.H. Robinson, B. van der Lei, H.J. Hoppen, J.W. Leenslag, A.J. Pennings, P. Nieuwenhuis, Nerve regeneration through a two-ply biodegradable nerve guide in the rat and the influence of ACTH4–9 nerve growth factor. Microsurgery 12, 412 (1991). doi:10.1002/micr.1920120608

    Article  PubMed  CAS  Google Scholar 

  14. M.E. Broz, D.L. VanderHart, N.R. Washburn, Structure and mechanical properties of poly (D, L-lactic acid)/poly(e-caprolactone) blends. Biomaterials 24, 4181 (2003). doi:10.1016/S0142-9612(03)00314-4

    Article  PubMed  CAS  Google Scholar 

  15. R.L. Reis, A.M. Cunha, Characterization of two biodegradable polymers of potential application within the biomaterials field. J. Mater. Sci. Mater. Med. 6, 786 (1995). doi:10.1007/BF00134318

    Article  CAS  Google Scholar 

  16. J. Spěváček, J. Brus, T. Divers, Y. Grohens, Solid-state NMR study of biodegradable starch/polycaprolactone blends. Eur. Polym. J. 43, 1866 (2007). doi:10.1016/j.eurpolymj.2007.02.021

    Article  CAS  Google Scholar 

  17. R. Dell’Erba, G. Groeninckx, G. Maglio, M. Malinconico, A. Migliozzi, Immiscible polymer blends of semicrystalline biocompatible components: thermal properties and phase morphology analysis of PLLA/PCL blends. Polymer (Guildf) 42, 7831 (2001). doi:10.1016/S0032-3861(01)00269-5

    Article  CAS  Google Scholar 

  18. L. Wang, W. Ma, R.A. Gross, S.P. McCarthy, Reactive compatibilization of biodegradable blends of poly (lactic acid) and poly (ε-caprolactone). Polym. Degrad. Stab. 59, 161 (1998). doi:10.1016/S0141-3910(97)00196-1

    Article  CAS  Google Scholar 

  19. P.N. Mohanna, G. Terenghi, M. Wiberg, Composite PHB-GGF conduit for long nerve gap repair: a long-term evaluation. J. Plast. Reconstr. Surg. Hand Surg. 39, 129 (2005). doi:10.1080/02844310510006295

    Article  Google Scholar 

  20. D.F. Kalbermatten, P.J. Kingham, D. Mahay, C. Mantovani, J. Pettersson, W. Raffoul, H. Balcin, G. Pierer, G. Terenghi, Fibrin matrix for suspension of regenerative cells in an artificial nerve conduit. J. Plast. Reconstr. Aesthet. Surg. 61, 669 (2008). doi:10.1016/j.bjps.2007.12.015

    Article  PubMed  CAS  Google Scholar 

  21. V. Crescenzi, G. Manzini, G. Calzolari, C. Borri, Thermodynamics of fusion of poly ß-propiolactone and poly ε-caprolactone. Comparative analysis of the melting of aliphatic polylactone and polyester chains. Eur. Polym. J. 8, 449 (1972). doi:10.1016/0014-3057(72)90109-7

    Article  CAS  Google Scholar 

  22. T. Freier, C. Kunze, K.-P. Schmitz, Solvent removal from solution-cast films of biodegradable polymers. J. Mater. Sci. Lett. 20, 1929 (2001). doi:10.1023/A:1013174400236

    Article  CAS  Google Scholar 

  23. M. Sun, S. Downes, Solvent-cast PCL films support the regeneration of NG108-15 nerve cells. in International Conference on Smart Materials and Nanotechnology in Engineering. Proceedings of the SPIE vol. 6423, p. 64230, July 2007

  24. M.S.K. Chong, C.N. Lee, S.H. Teoh, Characterization of smooth muscle cells on poly (ε-caprolactone) films. Mater. Sci. Eng. C 27, 309 (2007). doi:10.1016/j.msec.2006.03.008

    Article  CAS  Google Scholar 

  25. L.P.K. Ang, Z.Y. Cheng, R.W. Beuerman, S.H. Teoh, X. Zhu, D.T.H. Tan, The development of a serum-free derived bioengineered conjunctival epithelial equivalent using an ultrathin poly (ε-caprolactone) membrane substrate. Invest. Ophthalmol. Vis. Sci. 47, 105 (2006). doi:10.1167/iovs.05-0512

    Article  PubMed  Google Scholar 

  26. S.J. Huang, in Encyclopedia of Polymer Science and Engineering, vol. 2, ed. by H.F. Mark, N. Bikales, C.G. Overberger, G. Menges (Wiley, New York, 1985)

  27. F.C. Bragança, D.S. Rosa, Thermal, mechanical and morphological analysis of poly(ε-caprolactone), cellulose acetate and their blends. Polym. Adv. Technol. 14, 669 (2003). doi:10.1002/pat.381

    Article  CAS  Google Scholar 

  28. T.W. Hudson, G.R. Evans, C.E. Schmidt, Engineering strategies for peripheral nerve repair. Clin. Plast. Surg. 26, 617 (1999)

    PubMed  CAS  Google Scholar 

  29. V.B. Doolabh, M.C. Hertl, S.E. Mackinnon, The role of conduits in nerve repair: a review. Rev. Neurosci. 7, 47 (1996)

    PubMed  CAS  Google Scholar 

  30. W.F.A. den Dunnen, I. Stokroos, E.H. Blaauw, A. Holwerda, A.J. Pennings, P.H. Robinson, J.M. Schakenraad, Light-microscopic and electronmicroscopic evaluation of short-term nerve regeneration using a biodegradable poly (DL-lactide-ε- caprolactone) nerve guide. J. Biomed. Mater. Res. 31, 105 (1996). doi:10.1002/(SICI)1097-4636(199605)31:1<105::AID-JBM13>3.0.CO;2-M

    Article  Google Scholar 

  31. Y.-C. Huang, Y.-Y. Huang, Biomaterials and strategies for nerve regeneration. Artif. Organs 30, 514 (2006). doi:10.1111/j.1525-1594.2006.00253.x

    Article  PubMed  Google Scholar 

  32. Q. Cai, J. Bei, S. Wang, In vitro study on the drug release behaviour from polylactide-based blend matrices. Polym. Adv. Technol. 13, 534 (2002). doi:10.1002/pat.222

    Article  CAS  Google Scholar 

  33. K.S. Tiaw, S.H. Teoh, R. Chen, M.H. Hong, Processing methods of ultrathin poly(ε-caprolactone) films for tissue engineering applications. Biomacromolecules 8, 807 (2007). doi:10.1021/bm060832a

    Article  PubMed  CAS  Google Scholar 

  34. G.H. Borschel, K.F. Kia Jr., W.M. Kuzon, R.G. Dennis, Mechanical properties of acellular peripheral nerve. J. Surg. Res. 114, 133 (2003). doi:10.1016/S0022-4804(03)00255-5

    Article  PubMed  Google Scholar 

  35. N. Nicoli Aldini, M. Fini, M. Rocca, G. Giavaresi, R. Giardino, Guided regeneration with resorbable conduits in experimental peripheral nerve injuries. Int. Orthop. SICOT 24, 121 (2000). doi:10.1007/s002640000142

    Article  CAS  Google Scholar 

  36. G.E. Rutkowski, C.A. Heath, Development of a bioartificial nerve graft. II. Nerve regeneration in vitro. Biotechnol. Prog. 18, 373 (2002). doi:10.1021/bp020280h

    Article  PubMed  CAS  Google Scholar 

  37. M.F. Meek, W.F.A. den Dunnen, H. Bartels, P.H. Robinson, J.M. Schakenraad, Peripheral nerve regeneration and functional nerve recovery after reconstruction with thin-walled biodegradable poly (DL-lactide-ε-caprolactone) nerve guides. Cell Mater. 7, 53 (1997)

    CAS  Google Scholar 

  38. M.F. Meek, P.H. Robinson, I. Stokroos, E.H. Blaauw, G. Kors, W.F.A. den Dunnen, Electronmicroscopical evaluation of short-term nerve regeneration through a thin-walled biodegradable poly (DLLA-ε-CL) nerve guide filled with modified denatured muscle tissue. Biomaterials 22, 1177 (2001). doi:10.1016/S0142-9612(00)00340-9

    Article  PubMed  CAS  Google Scholar 

  39. T.B. Ducker, G.J. Hayes, Experimental improvements in the use of silastic cuff for peripheral nerve repair. J. Neurosurg. 28, 582 (1968)

    PubMed  CAS  Google Scholar 

  40. D. Simon, A. Holland, R. Shanks, Poly (caprolactone) thin film preparation, morphology, and surface texture. J. Appl. Polym. Sci. 103, 1287 (2007). doi:10.1002/app.25228

    Article  CAS  Google Scholar 

  41. M.F. Meek, W.F. den Dunnen, J.M. Schakenraad, P.H. Robinson, Long-term evaluation of functional nerve recovery after reconstruction with a thin-walled biodegradable poly (DL-Lactide-ε-caprolactone) nerve guide, using walking track analysis and electrostimulation tests. Microsurgery 19, 247 (1999). doi:10.1002/(SICI)1098-2752(1999)19:5<247::AID-MICR7>3.0.CO;2-E

    Article  PubMed  CAS  Google Scholar 

  42. S. Panseri, C. Cunha, J. Lowery, U.D. Carro, F. Taraballi, S. Amadio, A. Vescovi, F. Gelain, Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections. BMC Biotechnol. 8, 39 (2008). doi:10.1186/1472-6750-8-39

    Article  PubMed  CAS  Google Scholar 

  43. J. Wei, Y. Masao, T. Shinji, H. Masayuki, K. Eiji, B. Liu, O. Yutaka, Adhesion of mouse fibroblasts on hexamethyldisiloxane surfaces with wide range of wettability. J. Biomed. Mater. Res. 81, 66 (2007). doi:10.1002/jbm.b.30638

    Article  CAS  Google Scholar 

  44. A. Thapa, T.J. Webster, K.M. Haberstroh, Polymers with nano-dimensional surface features enhance bladder smooth muscle cell adhesion. J. Biomed. Mater. Res. 67A, 1374 (2003). doi:10.1002/jbm.a.20037

    Article  CAS  Google Scholar 

  45. A. Thapa, T.J. Webster, K.M. Haberstroh, Nano-structured polymers enhance bladder smooth muscle cell function. Biomaterials 24, 2915 (2003). doi:10.1016/S0142-9612(03)00123-6

    Article  PubMed  CAS  Google Scholar 

  46. R.J. Vance, D.C. Miller, A. Thapa, K.M. Haberstroh, T.J. Webster, Decreased fibroblast cell density on chemically degraded poly-lactic-co-glycolic acid, polyurethane, and polycaprolactone. Biomaterials 25, 2095 (2004). doi:10.1016/j.biomaterials.2003.08.064

    Article  PubMed  CAS  Google Scholar 

  47. H. Nishida, Y. Tokiwa, Confirmation of colonization of degrading bacterium strain SC-17 on poly(3-hydroxybutyrate) cast film. J. Environ. Polym. Degrad. 3, 187 (1995). doi:10.1007/BF02068673

    Article  CAS  Google Scholar 

  48. C.L.A.M. Vleggeert-Lankamp, G.C.W. de Ruiter, J.F.C. Wolfs, A.P. Pêgo, R.J. van den Berg, H.K.P. Feirabend, M.J.A. Malessy, E.A.J.F. Lakke, Pores in synthetic nerve conduits are beneficial to regeneration. J. Biomed. Mater. Res. 80A, 965 (2006). doi:10.1002/jbm.a.30941

    Article  CAS  Google Scholar 

  49. F.J. Rodriguez, N. Gomez, G. Perego, X. Navarro, Highly permeable polylactide-caprolactone nerve guides enhance peripheral nerve regeneration through long gaps. Biomaterials 20, 1489 (1999). doi:10.1016/S0142-9612(99)00055-1

    Article  PubMed  CAS  Google Scholar 

  50. A.P. Pêgo, A.A. Poot, D.W. Grijpma, J. Feijen, Copolymers of trimethylene carbonate and ε-caprolactone for porous nerve guides: synthesis and properties. J. Biomater. Sci. Polym. Ed. 12, 35 (2001). doi:10.1163/156856201744434

    Article  PubMed  Google Scholar 

  51. B.G. Uzman, G.M. Villegas, Mouse sciatic nerve regeneration through semipermeable tubes: a quantitative model. J. Neurosci. Res. 9, 325 (1983). doi:10.1002/jnr.490090309

    Article  PubMed  CAS  Google Scholar 

  52. C.-B. Jenq, R.E. Coggeshall, Permeable tubes increase the length of the gap that regenerating axons can span. Brain Res. 408, 239 (1987). doi:10.1016/0006-8993(87)90379-9

    Article  PubMed  CAS  Google Scholar 

  53. P. Aebischer, V. Guénard, S.R. Winn, R.F. Valentini, P.M. Galletti, Blind-ended semipermeable guidance channels support peripheral nerve regeneration in the absence of a distal nerve stump. Brain Res. 454, 179 (1988). doi:10.1016/0006-8993(88)90817-7

    Article  PubMed  CAS  Google Scholar 

  54. B. Knoops, H. Hurtado, P. van den Bosch de Aguilar, Rat sciatic nerve regeneration within an acrylic semipermeable tube and comparison with a silicone impermeable material. J. Neuropathol. Exp. Neurol. 49, 438 (1990)

    Article  PubMed  CAS  Google Scholar 

  55. K.L. Gibson, L. Remson, A. Smith, N. Satterlee, G.M. Strain, J.K. Daniloff, Comparison of nerve regeneration through different types of neural prostheses. Microsurgery 12, 80 (1991). doi:10.1002/micr.1920120205

    Article  PubMed  CAS  Google Scholar 

  56. R.D. Keeley, K.D. Nguyen, M.J. Stephanides, J. Padilla, J.M. Rosen, The artificial nerve graft: a comparison of blended elastomerhydrogel with polyglycolic acid conduits. J. Reconstr. Microsurg. 7, 93 (1991). doi:10.1055/s-2007-1006766

    Article  PubMed  CAS  Google Scholar 

  57. M. Siemionow, A. Sari, A contemporary overview of peripheral nerve research from the Cleveland Clinic Microsurgery Laboratory. Neurol. Res. 26, 218 (2004). doi:10.1179/016164104225013860

    Article  PubMed  Google Scholar 

  58. A.J. Vernadakis, H. Koch, S.E. Machinnon, Management of neuromas. Clin. Plast. Surg. 30, 247 (2003). doi:10.1016/S0094-1298(02)00104-9

    Article  PubMed  Google Scholar 

  59. H.M. Shabana, R.H. Olley, D.C. Bassett, B. Jungnickel, Phase separation induced by crystallization in blends of polycaprolactone and polystyrene: an investigation by etching and electron microscopy. J. Polym. 41, 5513 (2000). doi:10.1016/S0032-3861(99)00713-2

    Article  CAS  Google Scholar 

  60. C.S. Ng, S.H. Teoh, T.S. Chung, D.W. Hutmacher, Simultaneous biaxial drawing of poly (ε-caprolactone) films. Polymer (Guildf) 41, 5855 (2000). doi:10.1016/S0032-3861(99)00760-0

    Article  CAS  Google Scholar 

  61. R.J. Müller, I. Kleegerg, W.D. Decker, Biodegradation of polyesters containing aromatic constituints. J. Biotechnol. 86, 87 (2001). doi:10.1016/S0168-1656(00)00407-7

    Article  PubMed  Google Scholar 

  62. W.Y. Yam, J. Ismail, H.W. Kammer, H. Schmidt, C. KummerlÖwe, Polymer blends of poly (ε-caprolactone) and poly (vinyl methyl ether)-thermal properties and morphology. Polymer (Guildf) 40, 5545 (1999). doi:10.1016/S0032-3861(98)00807-6

    Article  CAS  Google Scholar 

  63. B.D. Ratner, A.S. Hoffman, F.J. Schoen, Biomaterials Science: An introduction to Materials in Medicine, 2nd edn. (Elsevier Inc., Amsterdam, 2004), pp. 67–80

    Google Scholar 

  64. D.L. Mooradian, P. Trescony, K. Keeney, L.T. Furcht, Effect of glow discharge surface modification of plasma TFE vascular graft material on fibronectin and laminin retention and endothelial cell adhesion. J. Surg. Res. 53, 74 (1992). doi:10.1016/0022-4804(92)90016-S

    Article  PubMed  CAS  Google Scholar 

  65. J.G. Steele, C. McFarland, B.A. Dalton, G. Johnson, M.D.M. Evans, C.R. Howlett, P.A. Underwood, Attachment of human-derived bone cells to tissue culture polystyrene and to unmodified polystyrene: the effect of surface chemistry upon initial cell attachment. J. Biomater. Sci. Polym. Ed. 5, 245 (1993). doi:10.1163/156856293X00339

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work is funded by Engineering and Physical Sciences Research Council (EPSRC). The authors would like to thank the technical staff at School of Materials for their kind assistance.

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  1. Materials Science Centre, Department of Engineering and Physical Sciences, The University of Manchester, Grosvenor Street, Manchester, M1 7HS, UK

    Mingzhu Sun & Sandra Downes

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Sun, M., Downes, S. Physicochemical characterisation of novel ultra-thin biodegradable scaffolds for peripheral nerve repair. J Mater Sci: Mater Med 20, 1181–1192 (2009). https://doi.org/10.1007/s10856-008-3671-3

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