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Published in: European Journal of Trauma and Emergency Surgery 2/2020

Open Access 01-04-2020 | Bone Defect | Original Article

From two stages to one: acceleration of the induced membrane (Masquelet) technique using human acellular dermis for the treatment of non-infectious large bone defects

Authors: René Danilo Verboket, Maximilian Leiblein, Maren Janko, Alexander Schaible, Jan Claas Brune, Katrin Schröder, Myriam Heilani, Charlotte Fremdling, Yannic Busche, Tanja Irrle, Ingo Marzi, Christoph Nau, Dirk Henrich

Published in: European Journal of Trauma and Emergency Surgery | Issue 2/2020

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Abstract

Introduction

The induced membrane technique for the treatment of large bone defects is a two-step procedure. In the first operation, a foreign body membrane is induced around a spacer, then, in the second step, several weeks or months later, the spacer is removed and the Membrane pocket is filled with autologous bone material. Induction of a functional biological membrane might be avoided by initially using a biological membrane. In this study, the effect of a human acellular dermis (hADM, Epiflex, DIZG gGmbH) was evaluated for the treatment of a large (5 mm), plate-stabilised femoral bone defect.

Material and Methods

In an established rat model, hADM was compared to the two-stage induced membrane technique and a bone defect without membrane cover. Syngeneous spongiosa from donor animals was used for defect filling in all groups. The group size in each case was n = 5, the induction time of the membrane was 3–4 weeks and the healing time after filling of the defect was 8 weeks.

Results

The ultimate loads were increased to levels comparable with native bone in both membrane groups (hADM: 63.2% ± 29.6% of the reference bone, p < 0.05 vs. no membrane, induced membrane: 52.1% ± 25.8% of the reference bone, p < 0.05 vs. no membrane) and were significantly higher than the control group without membrane (21.5%). The membrane groups were radiologically and histologically almost completely bridged by new bone formation, in contrast to the control Group where no closed osseous bridging could be observed.

Conclusion

The use of the human acellular dermis leads to equivalent healing results in comparison to the two-stage induced membrane technique. This could lead to a shortened therapy duration of large bone defects.
Literature
1.
go back to reference Nandi SK, Roy S, Mukherjee P, Kundu B, De DK, Basu D. Orthopaedic applications of bone graft and graft substitutes: a review. Indian Counc Med Res. 2010;132:15–30. Nandi SK, Roy S, Mukherjee P, Kundu B, De DK, Basu D. Orthopaedic applications of bone graft and graft substitutes: a review. Indian Counc Med Res. 2010;132:15–30.
2.
go back to reference Finkemeier CG. Bone-grafting and bone-graft substitutes. J Bone Jt Surg Am Vol. 2002;84:454.CrossRef Finkemeier CG. Bone-grafting and bone-graft substitutes. J Bone Jt Surg Am Vol. 2002;84:454.CrossRef
3.
go back to reference Kakar S, Duymaz A, Steinmann S, Shin AY, Moran SL. Vascularized medial femoral condyle corticoperiosteal flaps for the treatment of recalcitrant humeral nonunions. Microsurgery. 2011;31:85–92.CrossRef Kakar S, Duymaz A, Steinmann S, Shin AY, Moran SL. Vascularized medial femoral condyle corticoperiosteal flaps for the treatment of recalcitrant humeral nonunions. Microsurgery. 2011;31:85–92.CrossRef
4.
go back to reference Vögelin E, Jones NF, Huang JI, Brekke JH, Lieberman JR. Healing of a critical-sized defect in the rat femur with use of a vascularized periosteal flap, a biodegradable matrix, and bone morphogenetic protein. J Bone Jt Surg Am Vol. 2005;87:1323–31. Vögelin E, Jones NF, Huang JI, Brekke JH, Lieberman JR. Healing of a critical-sized defect in the rat femur with use of a vascularized periosteal flap, a biodegradable matrix, and bone morphogenetic protein. J Bone Jt Surg Am Vol. 2005;87:1323–31.
5.
go back to reference Karger C, Kishi T, Schneider L, Fitoussi F, Masquelet A-C. French Society of Orthopaedic Surgery and Traumatology (SoFCOT). Treatment of posttraumatic bone defects by the induced membrane technique. Orthop Traumatol Surg Res. 2012;98:97–102.CrossRef Karger C, Kishi T, Schneider L, Fitoussi F, Masquelet A-C. French Society of Orthopaedic Surgery and Traumatology (SoFCOT). Treatment of posttraumatic bone defects by the induced membrane technique. Orthop Traumatol Surg Res. 2012;98:97–102.CrossRef
6.
go back to reference Masquelet A-C. Muscle reconstruction in reconstructive surgery: soft tissue repair and long bone reconstruction. Langenbeck’s Arch Surg. 2003;388:344–6.CrossRef Masquelet A-C. Muscle reconstruction in reconstructive surgery: soft tissue repair and long bone reconstruction. Langenbeck’s Arch Surg. 2003;388:344–6.CrossRef
7.
go back to reference Iacobellis C, Berizzi A, Aldegheri R. Bone transport using the Ilizarov method: a review of complications in 100 consecutive cases. Strateg Trauma Limb Reconstr. 2010;5:17–22.CrossRef Iacobellis C, Berizzi A, Aldegheri R. Bone transport using the Ilizarov method: a review of complications in 100 consecutive cases. Strateg Trauma Limb Reconstr. 2010;5:17–22.CrossRef
8.
go back to reference Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: an update. Injury. 2005;36(Suppl 3):S20–S2727.CrossRef Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: an update. Injury. 2005;36(Suppl 3):S20–S2727.CrossRef
9.
go back to reference Masquelet A-C, 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.PubMed Masquelet A-C, 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.PubMed
10.
go back to reference Morelli I, Drago L, George DA, Gallazzi E, Scarponi S, Romanò CL. Masquelet technique: myth or reality? A systematic review and meta-analysis. Injury. 2016;47(Suppl 6):S68–S76.CrossRef Morelli I, Drago L, George DA, Gallazzi E, Scarponi S, Romanò CL. Masquelet technique: myth or reality? A systematic review and meta-analysis. Injury. 2016;47(Suppl 6):S68–S76.CrossRef
11.
go back to reference 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;47:325–34.CrossRef 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;47:325–34.CrossRef
12.
go back to reference Pelissier P, Martin D, Baudet J, Lepreux S, Masquelet A-C. Behaviour of cancellous bone graft placed in induced membranes. Br J Plast Surg. 2002;55:596–8.CrossRef Pelissier P, Martin D, Baudet J, Lepreux S, Masquelet A-C. Behaviour of cancellous bone graft placed in induced membranes. Br J Plast Surg. 2002;55:596–8.CrossRef
13.
go back to reference Pelissier P, Masquelet A-C, Bareille R, Pelissier SM, Amedee J. Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration. J Orthop Res. 2004;22:73–9.CrossRef Pelissier P, Masquelet A-C, Bareille R, Pelissier SM, Amedee J. Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration. J Orthop Res. 2004;22:73–9.CrossRef
14.
go back to reference Giannoudis PV, Faour O, Goff T, Kanakaris N, Dimitriou R. Masquelet technique for the treatment of bone defects: tips-tricks and future directions. Injury. 2011;42:591–8.CrossRef Giannoudis PV, Faour O, Goff T, Kanakaris N, Dimitriou R. Masquelet technique for the treatment of bone defects: tips-tricks and future directions. Injury. 2011;42:591–8.CrossRef
15.
go back to reference Pélissier P, Lefevre Y, Delmond S, Villars F, Vilamitjana-Amedee J. Influences of induced membranes on heterotopic bone formation within an osteo-inductive complex. Experimental study in rabbits. Ann Chir Plast Esthet. 2009;54:16–20.CrossRef Pélissier P, Lefevre Y, Delmond S, Villars F, Vilamitjana-Amedee J. Influences of induced membranes on heterotopic bone formation within an osteo-inductive complex. Experimental study in rabbits. Ann Chir Plast Esthet. 2009;54:16–20.CrossRef
16.
go back to reference Janko M, Dietz K, Rachor J, Sahm J, Schröder K, Schaible A, et al. Improvement of bone healing by neutralization of microRNA-335-5p, but not by neutralization of microRNA-92A in bone marrow mononuclear cells transplanted into a large femur defect of the rat. Tissue Eng Part A. 2019;25(1–2):55–68.CrossRef Janko M, Dietz K, Rachor J, Sahm J, Schröder K, Schaible A, et al. Improvement of bone healing by neutralization of microRNA-335-5p, but not by neutralization of microRNA-92A in bone marrow mononuclear cells transplanted into a large femur defect of the rat. Tissue Eng Part A. 2019;25(1–2):55–68.CrossRef
17.
go back to reference Nau C, Simon S, Schaible A, Seebach C, Schröder K, Marzi I, et al. Influence of the induced membrane filled with syngeneic bone and regenerative cells on bone healing in a critical size defect model of the rat’s femur. Injury. 2018;49:1721–31.CrossRef Nau C, Simon S, Schaible A, Seebach C, Schröder K, Marzi I, et al. Influence of the induced membrane filled with syngeneic bone and regenerative cells on bone healing in a critical size defect model of the rat’s femur. Injury. 2018;49:1721–31.CrossRef
18.
go back to reference Viateau V, Guillemin G, Bousson V, Oudina K, Hannouche D, Sedel L, et al. Long-bone critical-size defects treated with tissue-engineered grafts: a study on sheep. J Orthop Res. 2007;25:741–9.CrossRef Viateau V, Guillemin G, Bousson V, Oudina K, Hannouche D, Sedel L, et al. Long-bone critical-size defects treated with tissue-engineered grafts: a study on sheep. J Orthop Res. 2007;25:741–9.CrossRef
19.
go back to reference Gruber HE, Ode G, Hoelscher G, Ingram J, Bethea S, Bosse MJ. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Jt Res. 2016;5:106–15.CrossRef Gruber HE, Ode G, Hoelscher G, Ingram J, Bethea S, Bosse MJ. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Jt Res. 2016;5:106–15.CrossRef
20.
go back to reference Sanz M, Dahlin C, Apatzidou D, Artzi Z, Bozic D, Calciolari E, et al. Biomaterials and regenerative technologies used in bone regeneration in the craniomaxillofacial region: consensus report of group 2 of the 15th European workshop on periodontology on bone regeneration. J Clin Periodontol. 2019;46:82–91.CrossRef Sanz M, Dahlin C, Apatzidou D, Artzi Z, Bozic D, Calciolari E, et al. Biomaterials and regenerative technologies used in bone regeneration in the craniomaxillofacial region: consensus report of group 2 of the 15th European workshop on periodontology on bone regeneration. J Clin Periodontol. 2019;46:82–91.CrossRef
21.
go back to reference Tolstunov L, Hamrick JFE, Broumand V, Shilo D, Rachmiel A. Bone augmentation techniques for horizontal and vertical alveolar ridge deficiency in oral implantology. Oral Maxillofac Surg Clin. 2019;31:163–91.CrossRef Tolstunov L, Hamrick JFE, Broumand V, Shilo D, Rachmiel A. Bone augmentation techniques for horizontal and vertical alveolar ridge deficiency in oral implantology. Oral Maxillofac Surg Clin. 2019;31:163–91.CrossRef
22.
go back to reference Alises EC, Piedra M, Aragón TG, Quevedo M. Applications of tissue engineering in reparation of abdominal wall defects. Actual Med. 2015;100(794):32–6.CrossRef Alises EC, Piedra M, Aragón TG, Quevedo M. Applications of tissue engineering in reparation of abdominal wall defects. Actual Med. 2015;100(794):32–6.CrossRef
23.
go back to reference Debels H, Hamdi M, Abberton K, Morrison W. Dermal matrices and bioengineered skin substitutes: a critical review of current options. Plast Reconstr Surg Glob Open. 2015;3:e284.CrossRef Debels H, Hamdi M, Abberton K, Morrison W. Dermal matrices and bioengineered skin substitutes: a critical review of current options. Plast Reconstr Surg Glob Open. 2015;3:e284.CrossRef
24.
go back to reference Vitacolonna M, Mularczyk M, Herrle F, Schulze TJ, Haupt H, Oechsner M, et al. Effect on the tensile strength of human acellular dermis (Epiflex®) of in-vitro incubation simulating an open abdomen setting. BMC Surg BioMed Cent. 2014;14:7–7.CrossRef Vitacolonna M, Mularczyk M, Herrle F, Schulze TJ, Haupt H, Oechsner M, et al. Effect on the tensile strength of human acellular dermis (Epiflex®) of in-vitro incubation simulating an open abdomen setting. BMC Surg BioMed Cent. 2014;14:7–7.CrossRef
25.
go back to reference 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;44:649–65.CrossRef 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;44:649–65.CrossRef
26.
go back to reference Rössner E, Smith MD, Petschke B, Schmidt K, Vitacolonna M, Syring C, et al. Epiflex® a new decellularised human skin tissue transplant: manufacture and properties. Cell Tissue Bank. 2010;12:209–17.CrossRef Rössner E, Smith MD, Petschke B, Schmidt K, Vitacolonna M, Syring C, et al. Epiflex® a new decellularised human skin tissue transplant: manufacture and properties. Cell Tissue Bank. 2010;12:209–17.CrossRef
27.
go back to reference Seebach C, Henrich D, Schaible A, Relja B, Jugold M, Bonig H, et al. Cell-based therapy by implanted human bone marrow-derived mononuclear cells improved bone healing of large bone defects in rats. Tissue Eng Part A. 2015;21:1565–78.CrossRef Seebach C, Henrich D, Schaible A, Relja B, Jugold M, Bonig H, et al. Cell-based therapy by implanted human bone marrow-derived mononuclear cells improved bone healing of large bone defects in rats. Tissue Eng Part A. 2015;21:1565–78.CrossRef
28.
go back to reference Seebach C, Henrich D, Kahling C, Wilhelm K, Tami AE, Alini M, et al. Endothelial progenitor cells and mesenchymal stem cells seeded onto beta-TCP granules enhance early vascularization and bone healing in a critical-sized bone defect in rats. Tissue Eng Part A. 2010;16:1961–70.CrossRef Seebach C, Henrich D, Kahling C, Wilhelm K, Tami AE, Alini M, et al. Endothelial progenitor cells and mesenchymal stem cells seeded onto beta-TCP granules enhance early vascularization and bone healing in a critical-sized bone defect in rats. Tissue Eng Part A. 2010;16:1961–70.CrossRef
29.
go back to reference Henrich D, Seebach C, Nau C, Basan S, Relja B, Wilhelm K, Schaible A, Frank J, Barker J, Marzi I. Establishment and characterization of the Masquelet induced membrane technique in a rat femur critical-sized defect model. J Tissue Eng Regen Med. 2016;10(10):E382–E396396. https://doi.org/10.1002/term.1826[Epub 2013 Nov 8 PubMed PMID: 24668794].CrossRefPubMed Henrich D, Seebach C, Nau C, Basan S, Relja B, Wilhelm K, Schaible A, Frank J, Barker J, Marzi I. Establishment and characterization of the Masquelet induced membrane technique in a rat femur critical-sized defect model. J Tissue Eng Regen Med. 2016;10(10):E382–E396396. https://​doi.​org/​10.​1002/​term.​1826[Epub 2013 Nov 8 PubMed PMID: 24668794].CrossRefPubMed
30.
go back to reference Henrich D, Seebach C, Verboket R, Schaible A, Marzi I, Bönig H. The osteo-inductive activity of bone-marrow-derived mononuclear cells resides within the CD14+ population and is independent of the CD34+ population. Eur Cell Mater. 2018;35:165–77.CrossRef Henrich D, Seebach C, Verboket R, Schaible A, Marzi I, Bönig H. The osteo-inductive activity of bone-marrow-derived mononuclear cells resides within the CD14+ population and is independent of the CD34+ population. Eur Cell Mater. 2018;35:165–77.CrossRef
31.
go back to reference Garvey W, Fathi A, Bigelow F, Carpenter B, Jimenez C. Improved movat pentachrome stain. Stain Technol. 1986;61:60–2.CrossRef Garvey W, Fathi A, Bigelow F, Carpenter B, Jimenez C. Improved movat pentachrome stain. Stain Technol. 1986;61:60–2.CrossRef
32.
go back to reference Seebach C, Henrich D, Schaible A, Relja B, Jugold M, Bonig H, et al. Cell-based therapy by implanted human bone marrow-derived mononuclear cells improved bone healing of large bone defects in rats. Tissue Eng Part A. 2015;21:1565–78.CrossRef Seebach C, Henrich D, Schaible A, Relja B, Jugold M, Bonig H, et al. Cell-based therapy by implanted human bone marrow-derived mononuclear cells improved bone healing of large bone defects in rats. Tissue Eng Part A. 2015;21:1565–78.CrossRef
33.
go back to reference Raven TF, Moghaddam A, Ermisch C, Westhauser F, Heller R, Bruckner T, et al. Use of Masquelet technique in treatment of septic and atrophic fracture nonunion. Injury. 2019;50(Suppl 3):40–54.CrossRef Raven TF, Moghaddam A, Ermisch C, Westhauser F, Heller R, Bruckner T, et al. Use of Masquelet technique in treatment of septic and atrophic fracture nonunion. Injury. 2019;50(Suppl 3):40–54.CrossRef
34.
go back to reference Mathieu L, Bilichtin E, Durand M, de l'Escalopier N, Murison JC, Collombet J-M, et al. Masquelet technique for open tibia fractures in a military setting. Eur J Trauma Emerg Surg. 2019;45:346–7. Mathieu L, Bilichtin E, Durand M, de l'Escalopier N, Murison JC, Collombet J-M, et al. Masquelet technique for open tibia fractures in a military setting. Eur J Trauma Emerg Surg. 2019;45:346–7.
35.
go back to reference Gagyi SM, 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;36:2228–38.CrossRef Gagyi SM, 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;36:2228–38.CrossRef
36.
go back to reference Liu K, Wang Y, Sun Y, Qi X, Tian L, Zhao Y, et al. Masquelet technique combined with artificial dermis for the treatment of bone and soft tissue defects in rabbits. Zhongguo Xiu Fu Chong Jian Wai Zhi. 2019;33:578–85. Liu K, Wang Y, Sun Y, Qi X, Tian L, Zhao Y, et al. Masquelet technique combined with artificial dermis for the treatment of bone and soft tissue defects in rabbits. Zhongguo Xiu Fu Chong Jian Wai Zhi. 2019;33:578–85.
37.
go back to reference Vitacolonna M, Belharazem D, Hohenberger P, Roessner ED. In-vivo quantification of the revascularization of a human acellular dermis seeded with EPCs and MSCs in co-culture with fibroblasts and pericytes in the dorsal chamber model in pre-irradiated tissue. Cell Tissue Bank. 2016;18:27–43.CrossRef Vitacolonna M, Belharazem D, Hohenberger P, Roessner ED. In-vivo quantification of the revascularization of a human acellular dermis seeded with EPCs and MSCs in co-culture with fibroblasts and pericytes in the dorsal chamber model in pre-irradiated tissue. Cell Tissue Bank. 2016;18:27–43.CrossRef
38.
go back to reference Aaboe M, Pinholt EM, Hjorting-Hansen E. Healing of experimentally created defects: a review. Br J Oral Maxillofac Surg. 1995;33:312–8.CrossRef Aaboe M, Pinholt EM, Hjorting-Hansen E. Healing of experimentally created defects: a review. Br J Oral Maxillofac Surg. 1995;33:312–8.CrossRef
Metadata
Title
From two stages to one: acceleration of the induced membrane (Masquelet) technique using human acellular dermis for the treatment of non-infectious large bone defects
Authors
René Danilo Verboket
Maximilian Leiblein
Maren Janko
Alexander Schaible
Jan Claas Brune
Katrin Schröder
Myriam Heilani
Charlotte Fremdling
Yannic Busche
Tanja Irrle
Ingo Marzi
Christoph Nau
Dirk Henrich
Publication date
01-04-2020
Publisher
Springer Berlin Heidelberg
Keyword
Bone Defect
Published in
European Journal of Trauma and Emergency Surgery / Issue 2/2020
Print ISSN: 1863-9933
Electronic ISSN: 1863-9941
DOI
https://doi.org/10.1007/s00068-019-01296-x

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