ساخت و ارزیابی سازگاری سلولی و زیست‌تخریب ‌پذیری برون‌تن کامپوزیت 3PGS/CaTiO برای کاربرد به عنوان Conduit عصبی

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 دانشجوی کارشناسی ارشد، گروه مهندسی پزشکی- زیست‌مواد، دانشکده‌ی فن‌آوری‌های نوین پزشکی و کمیته‌‌ی تحقیقات دانشجویی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

2 استادیار، گروه بیومتریال، مهندسی بافت و نانوتکنولوژی پزشکی، دانشکده‌ی فن‌آوری‌های نوین پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

چکیده

مقدمه: Poly(glycerol sebacate) (PGS) پلیمری زیستی و نوین برای کاربرد‌های زیست‌پزشکی با سازگاری زیستی بالا و خواص مکانیکی نزدیک به بافت‌های نرم بدن و همچنین قابلیت تنظیم خواص در حین ساخت می‌باشد؛ اما این پلیمر، به تخریب زیستی به نسبت سریعی دچار می‌شود که به طور معمول، از نرخ بازسازی اعصاب محیطی بالاتر است و برای کاربرد به عنوان Conduit عصبی نیاز به بهبود خواص تخریبی دارد.روش‌ها: ابتدا، پیش‌پلیمر PGS سنتز و سپس معادل 5 درصد وزنی آن سرامیک کلسیم تیتانات (3CaTiO) که سازگاری زیستی بالایی دارد، به آن اضافه شد و مخلوط حاصل تحت عملیات پخت قرار گرفت تا استحکام آن افزایش یابد. بیوکامپوزیت حاصل، مورد تصویربرداری میکروسکوپ الکترونی روبشی، طیف‌سنجی تبدیل Fourier فروسرخ (FTIR یا Fourier transform infrared spectroscopy)، آزمون تخریب زیستی برون‌تن و ارزیابی سمیت سلولی با سلول 929L قرار گرفت.یافته‌ها: در نهایت، کامپوزیتی با توزیع ذرات بالا به دست آمد که آزمون تبدیل Fourier فروسرخ از ایجاد پیوندی شمیایی بین دو پیش‌ساز آن حکایت داشت. زمان تخریب زیستی برون‌تن، 23 درصد کاهش در افت وزن دوره‌ی 60 روزه‌ی تخریب کامپوزیت نسبت به پلیمر خالص را نشان داد. نتایج کشت سلول، زیستایی بالای 90 درصد پس از 5 روز کشت برای این کامپوزیت نشان داد.نتیجه‌گیری: با توجه به نرخ تخریب زیستی، وزن مولکولی و سازگاری سلولی، می‌توان این کامپوزیت را برای کاربرد Conduit عصبی مورد ارزیابی‌های بیشتری قرار داد.

کلیدواژه‌ها

عنوان مقاله [English]

Fabrication and Evaluation of Cell-Compatibility and in-Vitro Biodegradation of PGS/CaTiO3 Composite for Nerve Conduit Application

نویسندگان [English]

  • Reza Naser 1
  • Anousheh Zargar-Kharazi 2
1 MSc Student, Department of Biomedical Engineering and Biomaterials, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
2 Assistant Professor, Department of Biomaterials, Tissue Engineering and Medical Nanotechnology, School of Advanced Medical Technology, Isfahan University of Medical Sciences, Isfahan, Iran
چکیده [English]

Background: Poly(glycerol sebacate) (PGS) is a novel biological polymer for biomedical application with high biocompatibility, mechanical properties near to soft tissues of body and a adaptability of properties during synthesis. But, this polymer tends to undergo rather rapid biodegradation which is usually faster than peripheral nerve regeneration and needs optimization of degradability properties for using as a nerve conduit.Methods: First, PGS pre-polymer was synthesized and then, equal to 5% of its weight, calcium titanate ceramic, which is highly biocompatible, was added to it and the acquired mixture was exposed to heat in vacuum oven to increase its strength. The obtained biocomposite came under scanning electron microscopy (SEM) image, Fourier transform infrared (FTIR) spectroscopy, in-vitro biodegradation and cytotoxicity evaluation.Findings: A composite with high particle distribution was obtained which represented a chemical bond between its two precursors. The in-vitro degradation time showed 23% reduction in overall weight loss for the composite in comparison to pure PGS over a period of 60 days degradation. The cell culture showed more than 90% of viability after 5 days of culture for the composite.Conclusion: Regarding to biodegradation rate, molecular mass and high cytocompatibility, this composite is encouraging enough to merit further investigation for nerve conduit application.

کلیدواژه‌ها [English]

  • Poly(glycerol sebacate)
  • Biocomposite
  • Calcium titanate

مراجع

  1. Mukhatyar V, Karumbaiah L, Yeh J, Bellamkonda RV. Tissue engineering strategies designed to realize the endogenous regenerative potential of peripheral nerves. Adv Mater 2009; 21(46): 4670-9.
  2. Siemionow M, Brzezicki G. Current techniques and concepts in peripheral nerve repair. In: Harris AR, Jenner P. International review of neurobiology. London, UK: Academic Press; 2009. p. 141-72.
  3. Jiang X, Lim SH, Mao HQ, Chew SY. Current applications and future perspectives of artificial nerve conduits. Exp Neurol 2010; 223(1): 86-101.
  4. Siemionow M, Bozkurt M, Zor F. Regeneration and repair of peripheral nerves with different biomaterials: review. Microsurgery 2010; 30(7): 574-88.
  5. Pabari A, Yang SY, Seifalian AM, Mosahebi A. Modern surgical management of peripheral nerve gap. J Plast Reconstr Aesthet Surg 2010; 63(12): 1941-8.
  6. Belkas JS, Shoichet MS, Midha R. Peripheral nerve regeneration through guidance tubes. Neurol Res 2004; 26(2): 151-60.
  7. Johnson EO, Soucacos PN. Nerve repair: experimental and clinical evaluation of biodegradable artificial nerve guides. Injury 2008; 39(Suppl 3): S30-S36.
  8. Chen MB, Zhang F, Lineaweaver WC. Luminal fillers in nerve conduits for peripheral nerve repair. Ann Plast Surg 2006; 57(4): 462-71.
  9. Lee SK, Wolfe SW. Peripheral nerve injury and repair. J Am Acad Orthop Surg 2000; 8(4): 243-52.
  10. Kim YT, Haftel VK, Kumar S, Bellamkonda RV. The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps. Biomaterials 2008; 29(21): 3117-27.
  11. Nichols CM, Brenner MJ, Fox IK, Tung TH, Hunter DA, Rickman SR, et al. Effects of motor versus sensory nerve grafts on peripheral nerve regeneration. Exp Neurol 2004; 190(2): 347-55.
  12. Kiernan J, Rajakumar R. Barr's the human nervous system: An anatomical viewpoint. 10th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2013.
  13. Pollard JD, Fitzpatrick L. An ultrastructural comparison of peripheral nerve allografts and autografts. Acta Neuropathol 1973; 23(2): 152-65.
  14. Moradzadeh A, Borschel GH, Luciano JP, Whitlock EL, Hayashi A, Hunter DA, et al. The impact of motor and sensory nerve architecture on nerve regeneration. Exp Neurol 2008; 212(2): 370-6.
  15. IJpma FF, Van De Graaf RC, Meek MF. The early history of tubulation in nerve repair. J Hand Surg Eur Vol 2008; 33(5): 581-6.
  16. Lundborg G. A 25-year perspective of peripheral nerve surgery: evolving neuroscientific concepts and clinical significance. J Hand Surg Am 2000; 25(3): 391-414.
  17. de Ruiter GC, Malessy MJ, Yaszemski MJ, Windebank AJ, Spinner RJ. Designing ideal conduits for peripheral nerve repair. Neurosurg Focus 2009; 26(2): E5.
  18. Ribeiro-Resende VT, Koenig B, Nichterwitz S, Oberhoffner S, Schlosshauer B. Strategies for inducing the formation of bands of Bungner in peripheral nerve regeneration. Biomaterials 2009; 30(29): 5251-9.
  19. Young RC, Wiberg M, Terenghi G. Poly-3-hydroxybutyrate (PHB): a resorbable conduit for long-gap repair in peripheral nerves. Br J Plast Surg 2002; 55(3): 235-40.
  20. Wang S, Cai Q, Hou J, Bei J, Zhang T, Yang J, et al. Acceleration effect of basic fibroblast growth factor on the regeneration of peripheral nerve through a 15-mm gap. J Biomed Mater Res A 2003; 66(3): 522-31.
  21. Allen RA, Wu W, Yao M, Dutta D, Duan X, Bachman TN, et al. Nerve regeneration and elastin formation within poly(glycerol sebacate)-based synthetic arterial grafts one-year post-implantation in a rat model. Biomaterials 2014; 35(1): 165-73.
  22. Sundback CA, Shyu JY, Wang Y, Faquin WC, Langer RS, Vacanti JP, et al. Biocompatibility analysis of poly(glycerol sebacate) as a nerve guide material. Biomaterials 2005; 26(27): 5454-64.
  23. Wang Y, Ameer GA, Sheppard BJ, Langer R. A tough biodegradable elastomer. Nat Biotechnol 2002; 20(6): 602-6.
  24. Krooka NM, LeBlona C, Jedlicka SS. In vitro examination of poly(glycerol sebacate) degradation kinetics: Effects of porosity and cure temperature. MRS Proceedings 2014; 1621: 87-92.
  25. Borschel GH, Kia KF, Kuzon WM, Jr., Dennis RG. Mechanical properties of acellular peripheral nerve. J Surg Res 2003; 114(2): 133-9.
  26. Galego N, Rozsa C, Sanchez R, Fung J, Analia V, Santo Tomas J. Characterization and application of poly(β-hydroxyalkanoates) family as composite biomaterials. Polymer Testing 2000; 19(5): 485-92.
  27. Mathew AP, Oksman K, Sain M. Mechanical properties of biodegradable composites from poly lactic acid (PLA) and microcrystalline cellulose (MCC). Applied Polymer 2005; 97(5): 2014-25.
  28. Wang Y, Kim YM, Langer R. In vivo degradation characteristics of poly(glycerol sebacate). J Biomed Mater Res 2003; 66A(1): 192-7.
  29. Gao J, Ensley AE, Nerem RM, Wang Y. Poly(glycerol sebacate) supports the proliferation and phenotypic protein expression of primary baboon vascular cells. J Biomed Mater Res A 2007; 83(4): 1070-5.
  30. Redenti S, Neeley WL, Rompani S, Saigal S, Yang J, Klassen H, et al. Engineering retinal progenitor cell and scrollable poly(glycerol-sebacate) composites for expansion and subretinal transplantation. Biomaterials 2009; 30(20): 3405-14.
  31. Liu Q, Tian M, Shi R, Zhang L, Chen D, Tian W. Structure and properties of thermoplastic poly(glycerol sebacate) elastomers originating from prepolymers with different molecular weights. Appl Polym 2007; 104(2): 1131-7.
  32. Puli VS, Pradhan DK, Riggs BC, Chrisey DB, Katiyar RS. Investigations on structure, ferroelectric, piezoelectric and energy storage properties of barium calcium titanate (BCT) ceramics. J Alloy Compd 2014; 584: 369-73.
  33. Aebischer P, Valentini RF, Dario P, Domenici C, Galletti PM. Piezoelectric guidance channels enhance regeneration in the mouse sciatic nerve after axotomy. Brain Res 1987; 436(1): 165-8.
  34. Chierzi S, Ratto GM, Verma P, Fawcett JW. The ability of axons to regenerate their growth cones depends on axonal type and age, and is regulated by calcium, cAMP and ERK. Eur J Neurosci 2005; 21(8): 2051-62.
  35. Zhang XF, Kehoe S, Adhi SK, Ajithkumar TG, Moane S, O'Shea H, et al. Composition–structure–property (Zn2+ and Ca2+ ion release) evaluation of Si–Na–Ca–Zn–Ce glasses: Potential components for nerve guidance conduits. Mater Sci Eng: C 2011; 31(3): 669-76.
  36. Guo XL, Lu XL, Dong DL, Sun ZJ. Characterization and optimization of glycerol/sebacate ratio in poly(glycerol-sebacate) elastomer for cell culture application. J Biomed Mater Res A 2014; 102(11): 3903-7.
  37. Li Y, Cook WD, Moorhoff C, Huang WC, Chen QZ. Synthesis, characterization and properties of biocompatible poly(glycerol sebacate) pre-polymer and gel. Polym Int 2013; 62(4): 534-47.
  38. Liang SL, Cook WD, Thouas GA, Chen QZ. The mechanical characteristics and in vitro biocompatibility of poly(glycerol sebacate)-bioglass elastomeric composites. Biomaterials 2010; 31(33): 8516-29.
  39. Robinson BW, Nickel EH. A useful new technique for mineralogy; the backscattered-electron/low vacuum mode of SEM operation. American Mineralogist 1979; 64(11-12): 1322-8.
  40. Evans GR, Brandt K, Katz S, Chauvin P, Otto L, Bogle M, et al. Bioactive poly(L-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration. Biomaterials 2002; 23(3): 841-8.
  41. Yang J, Webb AR, Ameer GA. Novel citric acid-based biodegradable elastomers for tissue engineering. ‎Adv Mater 2004; 16(6): 511-6.
  42. Bunge RP, Bunge MB. Interrelationship between Schwann cell function and extracellular matrix production. Trends Neurosci 1983; 6: 499-505.
  43. Liang SL, Yang XY, Fang XY, Cook WD, Thouas GA, Chen QZ. In vitro enzymatic degradation of poly (glycerol sebacate)-based materials. Biomaterials 2011; 32(33): 8486-96.
  44. Dubey AK, Tripathi G, Basu B. Characterization of hydroxyapatite-perovskite (CaTiO3) composites: phase evaluation and cellular response. J Biomed Mater Res B Appl Biomater 2010; 95(2): 320-9.
مجله دانشکده پزشکی اصفهان
دوره 33، شماره 361 - شماره پیاپی 361
بهمن و اسفند 1394
صفحه 2084-2091

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سابقه مقاله

  • تاریخ دریافت: 15 مرداد 1394
  • تاریخ بازنگری: 11 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

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