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An injectable hydrogel with or without drugs for prevention of epidural scar adhesion after laminectomy in rats

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Abstract

Epidural scarring occurs inevitably in the defect after spinal laminectomy, and thus how to prevent or reduce it becomes a challenging topic. In the present study, an injectable hydrogel and its dexamethasone (DEX)-loaded hydrogel systems were adopted to prevent epidural scarring in a postlaminectomy rat model. The hydrogel system composed of poly(D,L-lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers was a free-flowing sol at room temperature, and spontaneously turned into a semi-solid gel at body temperature. A lumbar 3 total laminectomy was performed on Sprague Dawley (SD) rats, and the efficacy of the injectable hydrogel with or without drugs in preventing epidural scar formation was evaluated via the gross anatomical observation and histological examination at one month post-surgery. The results demonstrate that the use of hydrogel alone reduced epidural scarring significantly, whereas the efficacy of the DEX-loaded hydrogels presented an irregular dose-dependency of drug and even the inappropriate drug doses resulted in the negative results. Therefore, the present study confirms that the PLGA-PEGPLGA hydrogel holds potential as a barrier device to decrease peridural scarring, and reveals that the sustained delivery of the steroid hormone DEX to prevent surgery-related adhesions in the laminectomy defect is complex. Moreover, our in vivo studies also remind the researchers to pay attention to the irregular dose-dependency of the hormone drugs.

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References

  1. Malmivaara, A., Slatis, P., Heliovaara, M., Sainio, P., Kinnunen, H., Kankare, J., Dalin-Hirvonen, N., Seitsalo, S., Herno, A., Kortekangas, P., Niinimaki, T., Ronty, H., Tallroth, K., Turunen, V., Knekt, P., Harkanen, T., Hurri, H. and Finnish Lumbar Spinal Res. Grp., Spine, 2007, 32: 1

    Article  Google Scholar 

  2. Samy, A.M. and Hardy, R.J., Neurol. Res., 1999, 21 Suppl 1: S5

    Google Scholar 

  3. Abitbol, J.J., Lincoln, T.L., Lind, B.I., Amiel, D., Akeson, W.H. and Garfin, S.R., Spine, 1994, 19: 1809

    Article  CAS  Google Scholar 

  4. Rowlingson, J., Anesth. Analg., 1999, 88: 240

    CAS  Google Scholar 

  5. Einhaus, S.L., Robertson, J.T., Dohan, F.C., Wujek, J.R. and Ahmad, S., Spine, 1997, 22: 1440

    Article  CAS  Google Scholar 

  6. Liu, S., Boutrand, J.P. and Tadie, M., J. Neurosurg., 2001, 94: 61

    Article  CAS  Google Scholar 

  7. Topsakal, C., Akpolat, N., Erol, F.S., Ozveren, M.F., Akdemir, I., Kaplan, M., Tiftikci, M. and Kilic, N., J. Neurosurg., 2004, 101: 295

    Article  Google Scholar 

  8. Yan, L., Li, X., Wang, J., Sun, Y., Wang, D., Gu, J., He, J., Hu, H., Chen, G., Wang, Q. and Feng, X., Eur. J. Pharmacol., 2013, 699: 194

    Article  CAS  Google Scholar 

  9. Karatay, M., Erdem, Y., Koktekir, E., Erkoc, Y.S., Caydere, M. and Bayar, M.A., Turk. Neurosurg., 2012, 22: 753

    Google Scholar 

  10. Sandoval, M.A. and Hernandez-Vaquero, D., Eur. Spine J., 2008, 17: 451

    Article  Google Scholar 

  11. Mastronardi, L., Pappagallo, M., Puzzilli, F. and Tatta, C., Neurosurgery, 2002, 50: 518

    Google Scholar 

  12. Kim, K.D., Wang, J.C., Robertson, D.P., Brodke, D.S., Olson, E.M., Duberg, A.C., BenDebba, M., Block, K.M. and diZerega, G.S., Spine, 2003, 28: 1080

    Google Scholar 

  13. Rhyne, A.L., Blumenthal, S.L., Frank, E.H., Hsu, K.Y., Kim, K.D., Youssef, J.A., Wang, J.C., Arnold, P., BenDebba, M., Block, K.M., Juarez, T.G., Chiacchierini, R.P., Ehmsen, R.J., Krelle, J.S., diZerega, G.S. and Oxiplex Clinical Study Grp., Spine, 2012, 37: 631

    Article  Google Scholar 

  14. Fan, C.J., Liao, L.Q., Zhang, C. and Liu, L.J., J. Mater. Chem. B., 2013, 1: 4251

    Article  CAS  Google Scholar 

  15. Wu, L.Y., Yu, L., Fu, X.H. and Li, Z.B., Chinese J. Polym. Sci., 2015, 33(8): 1140

    Article  CAS  Google Scholar 

  16. Zhao, Z.B., An, S.S., Xie, H.J. and Jiang, Y., Chinese J. Polym. Sci., 2015, 33(1): 173

    Article  CAS  Google Scholar 

  17. Zeng, W., Hu, W.K., Li, H., Jing, Y.H., Kang, H., Jiang, Q. and Zhang, C., Chinese J. Polym. Sci., 2014, 32(11): 1507

    Article  CAS  Google Scholar 

  18. Cigognini, D., Silva, D., Paloppi, S., and Gelain, F., J. Biomed. Nanotechnol., 2014, 10: 309

    Article  CAS  Google Scholar 

  19. Moon, H.J., Ko, D.Y., Park, M.H., Joo, M.K. and Jeong, B., Chem. Soc. Rev., 2012, 41: 4860

    Article  CAS  Google Scholar 

  20. Yu, L. and Ding, J.D., Chem. Soc. Rev., 2008, 37: 1473

    Article  CAS  Google Scholar 

  21. Zhang, Y.B., Ding, J.X., Xu, W.G., Wu, J., Chang, F., Zhuang, X.L., Chen, X.S. and Wang, J.C., Chinese J. Polym. Sci., 2014, 32(12): 1590

    Article  CAS  Google Scholar 

  22. Shen, W.J., Luan, J.B., Cao, L.P., Sun, J., Yu, L. and Ding, J.D., Biomacromolecules, 2015, 16: 105

    Article  CAS  Google Scholar 

  23. Zhang, Y.B., Ding, J.X., Sun, D.K., Sun, H., Zhuang, X.L., Chang, F., Wang, J.C. and Chen, X.S., Mater. Sci. Eng. C-Mater. Biol. Appl., 2015, 49: 262

    Article  CAS  Google Scholar 

  24. Ni, P., Ding, Q.X., Fan, M., Liao, J.F., Qian, Z.Y., Luo, J.C., Li, X.Q., Luo, F., Yang, Z.M. and Wei, Y.Q., Biomaterials, 2014, 35: 236

    Article  CAS  Google Scholar 

  25. Li, Z.B., Zhang, Z.X., Liu, K.L., Ni, X.P. and Li, J., Biomacromolecules, 2012, 13: 3977

    Article  CAS  Google Scholar 

  26. Liu, C.D., Zhang, Z., Liu, K.L., Ni, X. and Li, J., Soft Matter, 2013, 9: 787

    Article  CAS  Google Scholar 

  27. Shim, M.S., Lee, H.T., Shim, W.S., Park, I., Lee, H., Chang, T., Kim, S.W. and Lee, D.S., J. Biomed. Mater. Res., 2002, 61: 188

    Article  CAS  Google Scholar 

  28. Yu, L., Chang, G.T., Zhang, H. and Ding, J.D., J Polym. Sci., Part A: Polym. Chem., 2007, 45: 1122

    Article  CAS  Google Scholar 

  29. Chen, C., Chen, L., Cao, L.P., Shen, W.J., Yu, L. and Ding, J.D., Rsc. Adv., 2014, 4: 8789

    Article  CAS  Google Scholar 

  30. Kwon, J.S., Kim, S.W., Kwon, D.Y., Park, S.H., Son, A.R., Kim, J.H. and Kim, M.S., Biomaterials, 2014, 35: 5337

    Article  CAS  Google Scholar 

  31. Park, M.H., Choi, B.G. and Jeong, B., Adv. Funct. Mater., 2012, 22: 5118

    Article  CAS  Google Scholar 

  32. Park, M.H., Yu, Y., Moon, H.J., Ko, D.Y., Kim, H.S., Lee, H., Ryu, K.H. and Jeong, B., Adv. Healthc. Mater., 2014, 3: 1782

    Article  CAS  Google Scholar 

  33. Il Kim, J., Kim, B., Chun, C., Lee, S.H. and Song, S.C., Biomaterials, 2012, 33: 4836

    Article  Google Scholar 

  34. Cho, J.K., Hong, J.M., Han, T., Yang, H.K. and Song, S.C., J. Drug Target., 2013, 21: 564

    Article  CAS  Google Scholar 

  35. Yu, L., Zhang, Z., Zhang, H. and Ding, J.D., Biomacromolecules, 2009, 10: 1547

    Article  CAS  Google Scholar 

  36. Ci, T.Y., Chen, L., Yu, L. and Ding, J.D., Sci. Rep., 2014, 4: 5473

    Article  CAS  Google Scholar 

  37. Chen, L., Ci, T.Y., Li, T., Yu, L. and Ding, J.D., Macromolecules, 2014, 47: 5895

    Article  CAS  Google Scholar 

  38. Bae, S.J., Joo, M.K., Jeong, Y., Kim, S.W., Lee, W.K., Sohn, Y.S. and Jeong, B., Macromolecules, 2006, 39: 4873

    Article  CAS  Google Scholar 

  39. Petit, A., Müller, B., Meijboom, R., Bruin, P., van de Manakker, F., Versluijs-Helder, M., de Leede, L.G.J., Doornbos, A., Landin, M., Hennink, W.E. and Vermonden, T., Biomacromolecules, 2013, 14: 3172

    Article  CAS  Google Scholar 

  40. Zhang, Z., Ni, J., Chen, L., Yu, L., Xu, J.W. and Ding, J.D., Biomaterials, 2011, 32: 4725

    Article  CAS  Google Scholar 

  41. Yu, L., Zhang, H. and Ding, J.D., Angew. Chem.-Int. Edit., 2006, 45: 2232

    Article  CAS  Google Scholar 

  42. Yu, L., Zhang, Z. and Ding, J.D., Biomacromolecules, 2011, 12: 1290

    Article  CAS  Google Scholar 

  43. Lei, K.W., Shen, W.J., Cao, L.P., Yu, L. and Ding, J.D., Chem. Commun., 2015, 51: 6080

    Article  CAS  Google Scholar 

  44. Chang, G.T., Ci, T.Y., Yu, L. and Ding, J.D., J., Control. Release, 2011, 156: 21

    Article  CAS  Google Scholar 

  45. Li, K., Yu, L., Liu, X.J., Chen, C., Chen, Q.H. and Ding, J.D., Biomaterials, 2013, 34: 2834

    Article  CAS  Google Scholar 

  46. Yu, L., Hu, H.T., Chen, L., Bao, X.G., Li, Y.Z., Chen, L., Xu, G.H., Ye, X.J. and Ding, J.D., Biomater. Sci., 2014, 2: 1100

    Article  CAS  Google Scholar 

  47. Yu, L., Xu, W., Shen, W.J., Cao, L.P., Liu, Y., Li, Z.S. and Ding, J.D., Acta Biomater., 2014, 10: 1251

    Article  CAS  Google Scholar 

  48. Li, X.Q., Chen, L., Lin, H., Cao, L.P., Cheng, J.A., Dong, J., Yu, L. and Ding, J.D., J. Spinal Disord. Technol., 2015, DOI: 10.1097/bsd.0000000000000221

    Google Scholar 

  49. Yang, B., Gong, C.Y., Qian, Z.Y., Zhao, X., Li, Z.Y., Qi, X.R., Zhou, S.T., Zhong, Q.A., Luo, F. and Wei, Y.Q., BMC Biotechnol., 2010, 10: 65

    Article  Google Scholar 

  50. Gong, C.Y., Wu, Q.J., Liao, J.F., Qi, T.T., Yang, B., Wang, Y.J., Guo, G., Luo, F., Zhao, X., Wei, Y.Q. and Qian, Z.Y., J. Biomed. Nanotechnol., 2013, 9: 1984

    Article  CAS  Google Scholar 

  51. Fu, S.Z., Li, Z, Fan, J.M., Meng, X.H., Shi, K., Qu, Y, Yang, L.L., Wu, J.B., Fan, C.J., Luo, F. and Qian, Z.Y., J. Biomed. Nanotechnol., 2014, 9: 427

    Article  Google Scholar 

  52. Rhen, T. and Cidlowski, J.A., N. Engl. J. Med., 2005, 353: 1711

    Article  CAS  Google Scholar 

  53. Yu, L., Zhang, Z. and Ding, J.D., Macromol. Res., 2012, 20: 234

    Article  CAS  Google Scholar 

  54. Cao, L. P., Cao, B., Lu, C.J., Wang, G.W., Yu, L. and Ding, J.D., J. Mater. Chem. B., 2015, 3: 1268

    Article  CAS  Google Scholar 

  55. He, Y., Revel, M. and Loty, B., Spine, 1995, 20: 557

    Article  CAS  Google Scholar 

  56. Yu, L., Zhang, Z., Zhang, H. and Ding, J.D., Biomacromolecules, 2010, 11: 2169

    Article  CAS  Google Scholar 

  57. Benoist, M., Ficat, C., Baraf, P. and Cauchoix, J., Spine, 1980, 5: 432

    Article  CAS  Google Scholar 

  58. Fandino, J., Botana, C., Viladrich, A. and Gomezbueno, J., Acta Neurochir., 1993, 122: 102

    Article  CAS  Google Scholar 

  59. Kiviluoto, O., Acta Orthop. Scand., 1976, 164: 3

    Article  Google Scholar 

  60. Topsakal, C., Akpolat, N., Erol, F.S., Ozveren, M.F., Akdemir, I., Kaplan, M., Tiftikci, M. and Kilic, N., J. Neurosurg., 2004, 101: 295

    Article  Google Scholar 

  61. Klopp, L.S., Welch, W.C., Tai, J.W., Toth, J.M., Cornwall, G.B. and Turner, A.S., Neurosurg. Focus, 2004, 16: E2

    Article  Google Scholar 

  62. Ivanic, G.M., Pink, P.T., Schneider, F., Stuecker, M., Homann, N.C. and Preidler, K.W., Eur. Spine J., 2006, 15: 1360

    Article  Google Scholar 

  63. Broughton, G., Janis, J.E. and Attinger, C.E., Plast. Reconstr. Surg., 2006, 117: 12S

    Article  CAS  Google Scholar 

  64. Ozdemir, O., Calisaneller, T., Sonmez, E., Kiyici, H., Caner, H. and Altinors, N., Neurol. Res., 2010, 32: 1117

    Article  CAS  Google Scholar 

  65. Cekinmez, M., Sen, O., Atalay, B., Erdogan, B., Bavbek, M., Caner, H., Ozen, O. and Altinors, N., Neurol. Res., 2010, 32: 700

    Article  CAS  Google Scholar 

  66. Lee, H.W., Lee, H., Chung, H., Park, J.C., Shin, S.K., Lee, S.K., Lee, Y.C., Hong, J.H. and Kim, D.W., Surg. Endosc., 2014, 28: 2334

    Article  Google Scholar 

  67. Foulkes, G.D. and Robinson, J.J., Clin. Orthop. Rel. Res., 1990, 224

    Google Scholar 

  68. Debi, R., Halperin, N. and Mirovsky, Y., J. Spinal Disord. Tech., 2002, 15: 273

    Article  Google Scholar 

  69. Zentner, G.M., Rathi, R., Shih, C., McRea, J.C., Seo, M.H., Oh, H., Rhee, B.G., Mestecky, J., Moldoveanu, Z., Morgan, M. and Weitman, S., J. Control. Release, 2001, 72: 203

    Article  CAS  Google Scholar 

  70. Dilova, V., Zlatarova, V., Spirova, N., Filcheva, K., Pavlova, A. and Grigorova, P., Boll. Chim. Farm., 2004, 143: 20

    CAS  Google Scholar 

  71. Cekinmez, M., Erdogan, B., Tufan, K., Sarica, F.B., Ozen, O. and Caner, H., Neurol. Res., 2009, 31: 322

    Article  Google Scholar 

  72. Czarnetzki, C., Elia, N., Lysakowski, C., Dumont, L., Landis, B.N., Giger, R., Dulguerov, P., Desmeules, J. and Tramer, M.R., Jama-J. Am. Med. Assoc., 2008, 300: 2621

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. State Key Laboratory of Molecular Engineering of Polymers & Department of Macromolecular Science, Fudan University, Shanghai, 200433, China

    Lin Chen, Lu-ping Cao, Xi-lei Li, Lin Yu  (俞麟) & Jian-dong Ding

  2. Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Xiang-qian Li, Xi-lei Li, Jun-rong Meng & Jian Dong  (董健)

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  1. Lin Chen
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  2. Xiang-qian Li
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  3. Lu-ping Cao
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  4. Xi-lei Li
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  6. Jian Dong  (董健)
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Correspondence to Jian Dong  (董健) or Lin Yu  (俞麟).

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These two authors contributed equally to this work.

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Chen, L., Li, Xq., Cao, Lp. et al. An injectable hydrogel with or without drugs for prevention of epidural scar adhesion after laminectomy in rats. Chin J Polym Sci 34, 147–163 (2016). https://doi.org/10.1007/s10118-016-1740-5

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  • DOI: https://doi.org/10.1007/s10118-016-1740-5

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