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A pilot study: Alternative biomaterials in critical sized bone defect treatment

Published:November 09, 2017DOI:https://doi.org/10.1016/j.injury.2017.11.007

      Abstract

      Background

      Critical-sized bone defects are a significant challenge with limited effective reconstructive options. The Masquelet Technique (MT) offers a solution to help restore form and function. Although this technique has produced promising results; a clear mechanism has not been determined. Theories include that the induced membrane has osteogenic potential or the membrane acts as a physical barrier to prevent fibrous tissue ingrowth. We hypothesize the induced membrane acts primarily as a physical barrier and that a synthetic non-biological membrane will allow a comparable amount of bone volume in the defect site.

      Methods

      Ten New Zealand rabbit forelimbs (n = 10) were divided into three study groups. A critical sized defect of 3.5 cm in the ulna was created. In the control group, a traditional MT was performed (n = 4). The experimental arm varied by replacement of the PMMA with a non-porous (n = 3) or porous (150um) (n = 3) polytetrafluoroethylene (PTFE) membrane filled with allograft. Micro-CT analysis was done to compare bone volume to tissue volume ratios (BV/TV). Defect sections were examined histologically with alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and von kossa (VK) staining.

      Results

      MicroCT analysis comparing BV/TV between the control and experimental arms showed no difference. BV/TV of the MT was 7.77% ± 2.34 compared to porous 9.12% ± 3.66 and nonporous 9.76% ± 1.57 PTFE membranes (p1 = 0.761, p2 = 0.572, respectively). Histological sections from both samples stained for ALP and TRAP displayed osteoblastic and osteoclastic activity. There was a higher amount of ALP and TRAP positively stained cells near the native bone ends in comparison to the center of the defect, in both sample types.

      Conclusion and significance

      Replacing the induced membrane from the MT with a synthetic PTFE membrane illustrated that the membrane acts primarily as a functional barrier. Compared to the induced membrane, the PTFE membrane was able to display similar osteointegrative properties. These results allow for future optimization of the technique with the potential to further streamline towards a single stage procedure.

      Keywords

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      References

        • Schmitz J.P.
        • Hollinger J.O.
        The critical size defect as an experimental model for craniomandibulofacial nonunions.
        Clin Orthop Relat Res. 1986; 205: 299-308
        • Aurégan J.-C.
        • Bégué T.
        Induced membrane for treatment of critical sized bone defect: a review of experimental and clinical experiences.
        Int Orthop (SICOT). 2014; : 1-8https://doi.org/10.1007/s00264-014-2422-y
        • Wiese A.M.D.
        • Hans Pape C.M.D.F.
        Bone defects caused by high-energy injuries, bone loss, infected nonunions, and nonunions.
        Orthop Clin NA. 2010; 41: 1-4https://doi.org/10.1016/j.ocl.2009.07.003
        • Gugala Z.
        • Lindsey R.W.
        • Gogolewski S.
        New approaches in the treatment of critical-Size segmental defects in long bones.
        Macromol Symp. 2007; 253: 147-161https://doi.org/10.1002/masy.200750722
        • Pneumaticos S.G.
        • Triantafyllopoulos G.K.
        • Basdra E.K.
        • Papavassiliou A.G.
        Segmental bone defects: from cellular and molecular pathways to the development of novel biological treatments.
        J Cell Mol Med. 2010; 14: 2561-2569https://doi.org/10.1111/j.1582-4934.2010.01062.x
        • Biau D.J.
        • Pannier S.
        • Masquelet A.C.
        • Glorion C.
        Case report: reconstruction of a 16-cm diaphyseal defect after Ewing's resection in a child.
        Clin Orthop Relat Res. 2009; 467 (Epub 2008 Nov 14): 572-577https://doi.org/10.1007/s11999-008-0605-9
        • Villemagne T.
        • Bonnard C.
        • Accadbled F.
        • L'kaissi M.
        • de Billy B.
        • Sales de Gauzy J.
        Intercalary segmental reconstruction of long bones after malignant bone tumor resection using primary methyl methacrylate cement spacer interposition and secondary bone grafting: the induced membrane technique.
        J Pediatr Orthop. 2011; 31: 570-576https://doi.org/10.1097/BPO.0b013e31821ffa82
        • Chotel F.
        • Nguiabanda L.
        • Braillon P.
        • Kohler R.
        • Berard J.
        • Abelin-Genevois K.
        Induced membrane technique for reconstruction after bone tumor resection in children: a preliminary study.
        Orthop Traumatol Surg Res. 2012; 98: 301-308https://doi.org/10.1016/j.otsr.2011.11.008
        • Gouron R.
        • Deroussen F.
        • Juvet M.
        • Ursu C.
        • Plancq M.C.
        • Collet L.M.
        Early resection of congenital pseudarthrosis of the tibia and successful reconstruction using the Masquelet technique.
        J Bone Joint Surg Br. 2011; 93: 552-554https://doi.org/10.1302/0301-620X.93B4.25826
        • Pannier S.
        • Pejin Z.
        • Dana C.
        • Masquelet A.C.
        • Glorion C.
        Induced membrane technique for the treatment of congenital pseudarthrosis of the tibia: preliminary results of five cases.
        J Child Orthop. 2013; 7: 477-485https://doi.org/10.1007/s11832-013-0535-2
        • Gouron R.
        • Deroussen F.
        • Plancq M.C.
        • Collet L.M.
        Bone defect reconstruction in children using the induced membrane technique: a series of 14 cases.
        Orthop Traumatol Surg Res. 2013; 99 (Epub 2013 Sep 23): 837-843https://doi.org/10.1016/j.otsr.2013.05.005
        • Molina C.S.
        • Stinner D.J.
        • Obremskey W.T.
        Treatment of traumatic segmental long-Bone defects.
        JBJS Rev. 2014; 2 (e1–e1)https://doi.org/10.2106/JBJS.RVW.M.00062
        • Mauffrey C.
        • Barlow B.T.
        • Smith W.
        Management of segmental bone defects.
        J Am Acad Orthop Surg. 2015; 23: 143-153https://doi.org/10.5435/JAAOS-D-14-00018
        • DeCoster T.A.
        • Gehlert R.J.
        • Mikola E.A.
        • Pirela-Cruz M.A.
        Management of posttraumatic segmental bone defects.
        J Am Acad Orthop Surg. 2004; 12: 28-38
        • Aronson J.
        Current concepts review -limb -lengthening, skeletal reconstruction, and bone transport with the ilizarov method*.
        J Bone Joint Surg. 1997; 79: 1243-1258
        • 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: 596-598https://doi.org/10.1054/bjps.2002.3936
        • Myeroff C.
        • Archdeacon M.
        Autogenous bone graft: donor sites and techniques.
        J Bone Joint Surg. 2011; 93https://doi.org/10.2106/JBJS.J.01513
        • Giannoudis P.V.
        • Faour O.
        • Goff T.
        • Kanakaris N.
        • Dimitriou R.
        Masquelet technique for the treatment of bone defects: tips-tricks and future directions.
        Injury. 2011; 42: 591-598https://doi.org/10.1016/j.injury.2011.03.036
        • Mekhail A.O.
        • Abraham E.
        • Gruber B.
        • Gonzalez M.
        Bone transport in the management of posttraumatic bone defects in the lower extremity.
        J Trauma Acute Care Surg. 2004; 56: 368
        • Lasanianos Nikolaos G.
        • Kanakaris Nikolaos K.
        • Giannoudis Peter V.
        Current management of long bone large segmental defects.
        Orthop Trauma Vol. 2010; 24: 149-163
        • Motsitsi N.S.
        Masquelet’s technique for management of long bone defects: from experiment to clinical application.
        East Central Afr J Surg. 2012; 17: 1-5
        • Masquelet A.C.
        • Bégué T.
        Genou/Rachis-93. Reconstruction Des Os Longs Par Membrane Induite Et Auto-Greffe Spongieuse (Une Serie De 35 Cas).
        de l'Appareil. 2000;
        • Klaue K.
        • Knothe U.
        • Masquelet A.C.
        Effet Biologique Des Membranes À Corps Étranger Induites in Situ Sur La Consolidation Des Greffes D'os Spongieux.
        Rev Chir Orthop Suppl. 1995; https://doi.org/10.1002/jor.21252/full
        • Viateau V.
        • Guillemin G.
        • Calando Y.
        • Logeart D.
        • Oudina K.
        • Sedel L.
        • Hannouche D.
        • Bousson V.
        • Petite H.
        Induction of a barrier membrane to facilitate reconstruction of massive segmental diaphyseal bone defects: an ovine model.
        Vet Surg. 2006; 35: 445-452https://doi.org/10.1111/j.1532-950X.2006.00173.x
        • Precheur H.V.
        Bone graft materials.
        Dent Clin North Am. 2007; 51: 729-746https://doi.org/10.1016/j.cden.2007.03.004
        • Tarchala M.
        • Harvey E.J.
        • Barralet J.
        Biomaterial-Stabilized soft tissue healing for healing of critical-sized bone defects: the masquelet technique. adv healthcare mater.
        Adv Healthcare Mater. 2016; (n/a–n/a)https://doi.org/10.1002/adhm.201500793
        • Gouron R.
        • Petit L.
        • Boudot C.
        • Six I.
        • Brazier M.
        • Kamel S.
        • Mentaverri R.
        Osteoclasts and their precursors are present in the induced-membrane during bone reconstruction using the Masquelet technique.
        J Tissue Eng Regen Med. 2017; 11 (Epub 2014 Jun 12): 382-389https://doi.org/10.1002/term.1921
        • Masquelet A.C.
        Muscle reconstruction in reconstructive surgery: soft tissue repair and long bone reconstruction.
        Langenbeck's Arch Surg. 2003; 388: 344-346https://doi.org/10.1007/s00423-003-0379-1
        • Pelissier P.H.
        • AC M.
        Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration.
        J Orthop Res. 2004; : 1-7https://doi.org/10.1016/S0736-0266(03)00165-7
        • 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. 2013; 10 (Epub 2013 Nov 8): 382-396https://doi.org/10.1002/term.1826
        • Einhorn T.A.
        • Majeska R.J.
        • Rush E.B.
        • Levine P.M.
        • Horowitz M.C.
        The expression of cytokine activity by fracture callus.
        J Bone Miner Res. 1995; 10: 1272-1281https://doi.org/10.1002/jbmr.5650100818
        • Bolander M.E.
        Regulation of fracture repair by growth factors.
        Proc Soc Exp Biol Med. 1992; 200: 165-170
        • Dimitriou R.
        • Mataliotakis G.I.
        • Calori G.M.
        • Giannoudis P.V.
        The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence.
        BMC Med. 2012; 10: 81https://doi.org/10.1186/1741-7015-10-81
        • Retzepi M.
        • Donos N.
        Guided Bone Regeneration: biological principle and therapeutic applications.
        Clin Oral Implants Res. 2010; 21: 567-576https://doi.org/10.1111/j.1600-0501.2010.01922.x
        • Jung R.E.
        • Kokovic V.
        • Jurisic M.
        • Yaman D.
        • Subramani K.
        • Weber F.E.
        Guided bone regeneration with a synthetic biodegradable membrane: a comparative study in dogs.
        Clin Oral Implants Res. 2010; 22: 802-807https://doi.org/10.1111/j.1600-0501.2010.02068.x
        • Gottlow J.
        Guided Tissue Regeneration using bioresorbable and nonresorbable devices.
        J Jap Soc Periodontol. 2010; 35 (1–1)
        • Hurley L.A.
        • Bassett C.A.L.
        • Stinchfield F.E.
        The role of soft tissues in osteogenesis.
        J Bone Joint Surg Am. 1959; 41-A: 1243-1266
        • Ogiso B.
        • Hughes F.J.
        • Melcher A.H.
        • McCulloch C.A.G.
        Fibroblasts inhibit mineralised bone nodule formation by rat bone marrow stromal cells In vitro.
        J Cell Physiol. 1991; 146: 442-450
        • Giannoudis P.V.
        • Einhorn T.A.
        • Marsh D.
        Fracture healing: the diamond concept.
        Injury. 2007; 38: S3-S6https://doi.org/10.1016/S0020-1383(08)70003-2
        • Zhou J.
        • Dong J.
        Lin Yunfeng Vascularization in the Bone Repair, Osteogenesis. InTech, 2012https://doi.org/10.5772/36325 (Available from: https://www.intechopen.com/books/osteogenesis/vascularization-in-the-bone-repair)
        • Pineda L.M.
        • Busing M.
        • Meinig R.P.
        • Gogolewski S.
        Bone regeneration with resorbable polymeric membranes. III. Effect of poly(L-lactide) membrane pore size on the bone healing process in large defects.
        J Biomed Mater Res. 1996; 31: 385-394https://doi.org/10.1002/(SICI)1097-4636(199607)31:3<385:AID-JBM13>3.0.CO;2-I
        • El Backly Rania M.
        • Chiapale Danilo
        • Muraglia Anita
        • Tromba Giuliana
        • Ottonello Chiara
        • Santolini Federico
        • Cancedda Ranieri
        • Mastrogiacomo Maddalena
        A modified rabbit ulna defect model for evaluating periosteal substitutes in bone engineering: a pilot study.
        Front Bioeng Biotechnol. 2015; https://doi.org/10.3389/fbioe.2014.00080/abstract
        • Horner E.A.
        • Kirkham J.
        • Wood D.
        • Curran S.
        • Smith M.
        • Thomson B.
        • Yang X.B.
        Long bone defect models for tissue engineering applications: criteria for choice.
        Tissue Eng Part B Rev. 2010; 16: 263-271https://doi.org/10.1089/ten.TEB.2009.0224
        • Shand J.M.
        • Heggie A.A.C.
        • Holmes A.D.
        • Holmes W.
        Allogeneic bone grafting of calvarial defects: an experimental study in the rabbit.
        Int J Oral Maxillofac Surg. 2002; 31: 525-531https://doi.org/10.1054/ijom.2002.0281
        • Aho O.-M.
        • Lehenkari P.
        • Ristiniemi J.
        • Lehtonen S.
        • Risteli J.
        • Leskelä H.-V.
        The mechanism of action of induced membranes in bone repair.
        J Bone Joint Surg Am. 2013; 95: 597-604https://doi.org/10.2106/JBJS.L.00310
        • Wong T.M.
        • Lau T.W.
        • Li X.
        • Fang C.
        • Yeung K.
        • Leung F.
        Masquelet technique for treatment of posttraumatic bone defects.
        Sci World J. 2014; 2014: 710302-710305https://doi.org/10.1155/2014/710302
        • Masquelet A.C.
        • Fitoussi F.
        • Bégué T.
        • Muller G.P.
        Reconstruction of the long bones by the induced membrane and spongy autograft.
        Ann Chir Plast Esthet. 2000; 45: 346-353
        • Saran U.
        • Gemini Piperni S.
        • Chatterjee S.
        Role of angiogenesis in bone repair.
        Arch Biochem Biophys. 2014; 561: 109-117https://doi.org/10.1016/j.abb.2014.07.006
        • Hing K.A.
        Bone repair in the twenty-first century: biology, chemistry or engineering?.
        Philos Trans A Math Phys Eng Sci. 1825; 2004: 2821-2850https://doi.org/10.1098/rsta.2004.1466
        • Breitbart A.S.
        • Ablaza V.J.
        Implant materials.
        in: Thorne C.H. Grabb and Smiths Plastic Surgery. 6th ed. 2006: 1-8
        • de Monès E.
        • Schlaubitz S.
        • Oliveira H.
        • d'Elbée J.M.
        • Bareille R.
        • Bourget C.
        • Couraud L.
        • Fricain J.C.
        Comparative study of membranes induced by PMMA or silicone in rats, and influence of external radiotherapy.
        Acta Biomater. 2015; 19: 119-127https://doi.org/10.1016/j.actbio.2015.03.005
        • Madison R.D.
        • da Silva C.
        • Dikkes P.
        • Sidman Chiu R.L.T.H.
        Peripheral nerve regeneration with entubulation repair: comparison of biodegradeable nerve guides versus polyethylene tubes and the effects of a laminin-containing gelm.
        Exp Neurolm. 1987; 95: 378-390
        • Najafpour A.
        • Mohammadi R.
        • Faraji D.
        • Amini K.
        Local administration of prostaglandin E1 combined with silicone chamber improves peripheral nerve regeneration.
        Int J Surg. 2013; 11: 1010-1015https://doi.org/10.1016/j.ijsu.2013.05.034
        • Chiu Y.C.
        • Cheng M.H.
        • Engel H.
        • Kao S.W.
        • Larson J.C.
        • Gupta S.
        • Brey E.M.
        The role of pore size on vascularization and tissue remodeling in PEG hydrogels.
        Biomaterials. 2011; 32: 6045-6051https://doi.org/10.1016/j.biomaterials.2011.04.066