Comparison between the induced membrane technique and distraction osteogenesis in treating segmental bone defects: An experimental study in a rat model

Autoři: Zhen Shen aff001;  Haixiong Lin aff001;  Guoqian Chen aff003;  Yan Zhang aff001;  Zige Li aff001;  Ding Li aff001;  Lei Xie aff004;  Yue Li aff005;  Feng Huang aff005;  Ziwei Jiang aff005
Působiště autorů: First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China aff001;  Department of Orthopaedics, First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou, Hunan, China aff002;  Fifth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China aff003;  Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China aff004;  Department of Orthopaedics, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226839


Previous studies have suggested that treatment plans for segmental bone defects (SBDs) are affected by the bone defect sizes. If the selected treatment was not the most appropriate, it would not contribute to bone healing, but increase complications. The induced membrane technique (IM) and distraction osteogenesis (DO) have been proved to be effective in treating SBDs. However, the differences between the two in therapeutic effects on SBDs with different sizes are still unclear. Thus, we aimed to observe the effects of IM and DO on different sizes of SBDs and to further determine what method is more appropriate for what defect size. Rat models of 4-, 6-and 8-mm mid-diaphyseal defects using IM and DO techniques were established. X-rays, micro-CT, histological and immunohistochemical examinations were performed to assess bone repair. Faster bone formation rate, shorter treatment duration, higher expressions of OPN and OCN and higher parameters of bone properties including bone mineral density (BMD), bone volume/total tissue volume (BV/TV), mineral apposition rate (MAR) and mineral surface/bone surface (MS/BS) were found in 4-mm SBDs treated with DO than in those with IM treatment. However, the results were reversed and IM outperformed DO in bone repair capacity for 8-mm SBDs, while no significant difference emerges in the case of 6-mm SBDs. This study suggests that the therapeutic effects of IM and DO may be subjected to sizes of bone defects and the best treatment size of defects is different between the two. For small-sized SBDs, DO may be more suitable and efficient than IM, but IM has advantages over DO for over-sized SBDs, while DO and IM show similar bone repair capability in moderate-sized SBDs, which would offer a new insight into how to choose DO and IM for SBDs in clinical practice and provide references for further clinical research.

Klíčová slova:

Bone development – Bone imaging – Histology – Ossification – Surgical and invasive medical procedures – Tissue repair


1. Rustom LE, Poellmann MJ, Wagoner Johnson AJ. Mineralization in micropores of calcium phosphate scaffolds. Acta Biomater. 2019; 83:435–455. 30408560.

2. Desai BM. Osteobiologics. Am J Orthop (Belle Mead NJ). 2007; 36:8–11. 17547352.

3. Tiemann AH, Schmidt HG, Braunschweig R. Strategies for the analysis of osteitic bone defects at the diaphysis of long bones. Strategies Trauma Limb Reconstr. 2009; 4:13–18. 19288056.

4. De Bastiani G, Aldegheri R, Renzi-Brivio L. Limb lengthening by callus distraction (callotasis). J Pediatr Orthop.1987; 7:129–134. doi: 10.1097/01241398-198703000-00002 3558791.

5. Rao N, Ziran BH. Treating osteomyelitis: antibiotics and surgery. Plast Reconstr Surg. 2011; 127 Suppl 1:177S–187S.

6. Verboket R, Leiblein M, Seebach C, Nau C, Janko M, Bellen M, et al. Autologous cell-based therapy for treatment of large bone defects: from bench to bedside. Eur J Trauma Emerg Surg. 2018; 44:649–665. 29352347.

7. El-Gammal TA, Shiha AE, El-Deen MA, El-Sayed A, Kotb MM, Addosooki AI, et al. Management of traumatic tibial defects using free vascularized fibula or Ilizarov bone transport: a comparative study. Microsurgery. 2008; 28:339–346. 18537173.

8. Lasanianos NG, Kanakaris NK, Giannoudis PV. Current management of long bone large segmental defects. Orthop Trauma. 2010; 24(2):149–163.

9. Marais LC. Bone transport through an induced membrane in the management of tibial bone defects resulting from chronic osteomyelitis. Strategies Trauma Limb Reconstr. 2015; 10:27–33. 25840909.

10. Masquelet AC, Fitoussi F, Begue T, Muller GP. Reconstruction of the long bones by the induced membrane and spongy autograft. Ann Chir Plast Esthet.2000; 45:346–53. 10929461.

11. Pelissier P, Martin D, Baudet J, Lepreux S, Masquelet AC. Behaviour of cancellous bone graft placed in induced membranes. Br J Plast Surg. 2002; 55:596–598. doi: 10.1054/bjps.2002.3936 12529009.

12. Ilizarov GA. The principles of the ilizarov method. Bull Hosp Jt Dis Orthop Inst 1988; 48:1–11. 2840141.

13. Li W, Zhu S, Hu J. Bone regeneration is promoted by orally administered bovine lactoferrin in a rabbit tibial distraction osteogenesis model. Clin Orthop Relat Res. 2015; 473:2383–2393. 25822454.

14. Ilizarov GA. Clinical and experimental data on bloodless lengthening of lower extremities. Eksp Khir Anesteziol.1969; 14(4):27–32. 5376256.

15. Toogood P. Critical-Sized Bone Defects: Sequence and Planning. J Orthop Trauma. 2017; 31 Suppl 5:S23–S26. 28938387.

16. Polyzois VD, Stathopoulos IP, Lampropoulou-Adamidou K, Vasiliadis ES, Vlamis J, Pneumaticos SG. Strategies for managing bone defects of the lower extremity. Clin Podiatr Med Surg. 2014; 31: 577–584. 25281517

17. Leiblein M, Henrich D, Fervers F, Kontradowitz K, Marzi I, Seebach C. Do antiosteoporotic drugs improve bone regeneration in vivo? Eur J Trauma Emerg Surg. 2019; 31028428.

18. Uzel AP, Lemonne F. Tibial segmental bone defect reconstruction by Ilizarov type bone transport in an induced membrane. Orthop Traumatol Surg Res. 2010; 96:194–198. 20417920.

19. Van Niekerk AH, Birkholtz FF, de Lange P, Tetsworth K, Hohmann E. Circular external fixation and cemented PMMA spacers for the treatment of complex tibial fractures and infected nonunions with segmental bone loss. J Orthop Surg (Hong Kong). 2017; 25:2309499017716242. 28639529.

20. Masquelet AC, Kishi T, Benko Pierre E. Very long-term results of post-traumatic bone defect Reconstruction by the induced membrane technique. Ortho Traumatol Surg Res. 2019; 105:159–166. 30639175.

21. Yin P, Ji Q, Li T, Li J, Li Z, Liu J, et al. A systematic review and meta-analysis of Ilizarov methods in the treatment of infected nonunion of tibiaand femur. PLos One. 2015; 10(11): e141973. 26529606.

22. Morelli I, Drago L, George DA, Gallazzi E, Sara Scarponi S, Romanò GL. Masquelet technique: myth or reality? a systematic review and meta-analysis. Injury. 2016; 47(Suppl6):S68–S76. 28040090.

23. Fan SD, Liu ZH, Hu WH, Wu GZ, Tang LH, Zhao LL. Excision of necrotic and infected tissues combined with induced membrane and external fixator technique for the treatment of chronic osteomyelitis in tibia after fracture operation. China J Orthop Trauma. 2017; 30(4):372–376. 29349992.

24. Tong K, Zhong Z, Peng Y, Lin C, Cao S, Yang Y, et al. Masquelet technique versus Ilizarov bone transport for reconstruction of lower extremity bone defects following posttraumatic osteomyelitis. Injury. 2017; 48:1616–1622. 28408083.

25. Akgun U, Canbek U. Masquelet technique versus Ilizarov bone transport for reconstruction of lower extremity bone defects following posttraumatic osteomyelitis. Injury. 2018; 49:738. 29366549.

26. Sun Y, Xu J, Xu L, Zhang J, Chan K, Pan X, et al. MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression. Sci Rep. 2017; 7:409. 28341855.

27. Henrich D, Seebach C, Nau C, Basan S, Relja B, Wilhelm K, et al. Establishment and characterization of the Masquelet induced membrane technique in a rat femur critical-sized defect model. J Tissue Eng Regen Med. 2016; 10:E382–E396. 24668794.

28. Goriainov V, Cook R, Latham JM, Dunlop DG, Oreffo RO. Bone and metal: An orthopaedic perspective on osseointegration of metals. Acta Biomater.2014;10(10):4043–4057. 24932769.

29. McBride-Gagyi S, Toth Z, Kim D, Ip V, Evans E, Watson JT, et al. Altering spacer material affects bone regeneration in the Masquelet technique in a rat femoral defect. J Orthop Res. 2018. 29424019.

30. Lane JM. Current approaches to experimental bone grafting. Orthop Clin North Am. 1987; 18: 213–225. 3550572.

31. Wu G, Liu Y, Iizuka T. The effect of a slow mode of BMP-2 delivery on the inflammatory response provoked by bone-defect-filling polymeric scaffolds. Biomaterials. 2010; 31: 7485–7493. 20638718.

32. O’Malley NT. Advances on the Masquelet technique using a cage and nail construct. Arch Orthop Trauma Surg. 2012; 132: 245–248. 22072192.

33. Giannoudis PV. Treatment of bone defects: Bone transport or the induced membrane technique? Injury. 2016; 47:291–292. 26879699

34. Yasui N, Sato M, Ochi T, Kimura T, Kawahata H, Kitamura Y, et al. Three modes of ossification during distraction osteogenesis in the rat. J Bone Joint Surg Br. 1997; 79: 824–830. 9331045

35. Ornitz DM. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev, 2002, 16(12):1446–1465. 12080084.

36. Aho OM, Lehenkari P, Ristiniemi J, Lehtonen S, Risteli J, Leskelä HV. The mechanism of action of induced membranes in bone repair. J Bone Joint Surg Am. 2013; 95:597–604. 23553294.

37. Nau C, Seebach C, Trumm A, Schaible A, Kontradowitz K, Meier S, et al. Alteration of Masquelet’s induced membrane characteristics by different kinds of antibiotic enriched bone cement in a critical size defect model in the rat’s femur. Injury. 2016; 47:325–334. 26652225.

38. Jin ZC, Cai QB, Zeng ZK, Li D, Li Y, Huang PZ, et al. Research progress on induced membrane technique for the treatment of segmental bone defect. China J Orthop Trauma. 2018; 31(5): 488–492. 29890813.

39. Ohyama M, Miyasaka Y, Sakurai M, Yokobori AT, Sasaki S. The mechanical behavior and morphological structure of callus in experimental callotasis. Biomed Mater Eng. 1994; 4:273–281. 7950875.

40. Forriol F, Denaro L, Longo UG, Taira H, Maffulli N, Denaro V. Bone lengthening osteogenesis, a combination of intramembranous and endochondral ossification: an experimental study in sheep. Strategies Trauma Limb Reconstr. 2010; 5:71–78. 21811902.

41. Labitzke R, Henze G. Biomechanics of the external fixation clamps. Unfallheilkunde. 1978; 81: 546–552. 684957.

42. Kummer FJ. Biomechanics of the Ilizarov external fixator. Bull Hosp Jt Dis Orthop Inst. 1989;49: 140–147. 2557936.

43. Osawa Y, Matsushita M, Hasegawa S, Esaki R, Fujio M, Ohkawara B, et al. Activated FGFR3 promotes bone formation via accelerating endochondral ossification in mouse model of distraction osteogenesis. Bone. 2017; 105:42–49. 28802681

44. Kojimoto H, Yasui N, Goto T, Matsuda S, Shimomura Y. Bone lengthening in rabbits by callus distraction. The role of periosteum and endosteum. J Bone Joint Surg Br. 1988; 70:543–549. 3403595.

45. Fujio M, Osawa Y, Matsushita M, Ogisu K, Tsuchiya S, Kitoh H, et al. A Mouse Distraction Osteogenesis Model. J Vis Exp. 2018; 30507900.

46. Chao EY, Aro HT, Lewallen DG, Kelly PJ. The effect of rigidity on fracture healing in external fixation. Clin Orthop. 1989; 241:24–35. 2647334.

47. Miller DL, Goswami T. A review of locking compression plate biomechanics and their advantages as internal fixators in fracture healing. Clin Biomech (Bristol, Avon). 2007; 22:1049–1062. 17904257.

48. Wu JJ, Shyr HS, Chao EY, Kelly PJ. Comparison of osteotomy healing under external fixation devices with different stiffness characteristics. J Bone Joint Surg. 1984; 66A:1258–64. 6490701.

49. Paino F, La Noce M, Giuliani A, De Rosa A, Mazzoni S, Laino L, et al. Human DPSCs fabricate vascularized woven bone tissue: a new tool in bone tissue engineering. Clin Sci (Lond). 2017; 131:699–713. 28209631.

50. Abou-Khalil R, Colnot C. Cellular and molecular bases of skeletal regeneration: what can we learn from genetic mouse models? Bone. 2014; 64:211–221. 24709685.

51. Flurkey KM, Currer J, Harrison DE. Chapter 20—Mouse Models in Aging Research. The Mouse in Biomedical Research (Second Edition). Edited by: James GF, Muriel TD, Fred WQ, Stephen WB, Christian EN, Abigail SL. 2007, Burlington: Academic Press, 637–672.

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2019 Číslo 12