Abstract
Critical-sized bone defects are defined as those that will not heal spontaneously within a patient’s lifetime. Current treatment options include vascularized bone grafts, distraction osteogenesis, and the induced membrane technique. The induced membrane technique is an increasingly utilized method with favorable results including high rates of union. Tissue engineering holds promise in the treatment of large bone defects due to advancement of stem cell biology, novel biomaterials, and 3D bioprinting. In this review, we provide an overview of the current operative treatment strategies of critical-sized bone defects as well as the current state of tissue engineering for such defects.
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References
Accadbled F, Mazeau P, Chotel F, Cottalorda J, Sales de Gauzy J, Kohler R (2013) Induced-membrane femur reconstruction after resection of bone malignancies: three cases of massive graft resorption in children. Orthop Traumatol Surg Res OTSR 99:479–483. doi:10.1016/j.otsr.2013.01.008
Ackermann PW, Hart DA (2013) Influence of comorbidities: neuropathy, vasculopathy, and diabetes on healing response quality. Adv Wound Care 2:410–421. doi:10.1089/wound.2012.0437
Aho OM, Lehenkari P, Ristiniemi J, Lehtonen S, Risteli J, Leskela HV (2013) The mechanism of action of induced membranes in bone repair. J Bone Jt Surg Am 95:597–604. doi:10.2106/JBJS.L.00310
Apard T, Bigorre N, Cronier P, Duteille F, Bizot P, Massin P (2010) Two-stage reconstruction of post-traumatic segmental tibia bone loss with nailing. Orthop Traumatol Surg Res OTSR 96:549–553. doi:10.1016/j.otsr.2010.02.010
Aponte-Tinao L, Farfalli GL, Ritacco LE, Ayerza MA, Muscolo DL (2012) Intercalary femur allografts are an acceptable alternative after tumor resection. Clin Orthop Relat Res 470:728–734. doi:10.1007/s11999-011-1952-5
Arai K, Toh S, Tsubo K, Nishikawa S, Narita S, Miura H (2002) Complications of vascularized fibula graft for reconstruction of long bones. Plast Reconstr Surg 109:2301–2306
Ardeshirylajimi A et al (2015) Enhanced osteoconductivity of polyethersulphone nanofibres loaded with bioactive glass nanoparticles in in vitro and in vivo models. Cell Prolif 48:455–464. doi:10.1111/cpr.12198
Ardeshirylajimi A, Hosseinkhani S, Parivar K, Yaghmaie P, Soleimani M (2013) Nanofiber-based polyethersulfone scaffold and efficient differentiation of human induced pluripotent stem cells into osteoblastic lineage. Mol Biol Rep 40:4287–4294. doi:10.1007/s11033-013-2515-5
Aronson J (1997) Limb-lengthening, skeletal reconstruction, and bone transport with the Ilizarov method. J Bone Jt Surg Am 79:1243–1258
Aronson J, Harrison B, Boyd CM, Cannon DJ, Lubansky HJ (1988) Mechanical induction of osteogenesis: the importance of pin rigidity. J Pediatr Orthop 8:396–401
Aronson J, Harrison B, Boyd CM, Cannon DJ, Lubansky HJ, Stewart C (1988) Mechanical induction of osteogenesis. Prelim Stud Ann Clin Lab Sci 18:195–203
Aronson J, Johnson E, Harp JH (1989) Local bone transportation for treatment of intercalary defects by the Ilizarov technique. Biomechanical and clinical considerations. Clin Orthop Relat Res 243:71–79
Bauer TW, Muschler GF (2000) Bone graft materials. An overview of the basic science. Clin Orthop Relat Res 371:10–27
Beris AE, Lykissas MG, Korompilias AV, Vekris MD, Mitsionis GI, Malizos KN, Soucacos PN (2011) Vascularized fibula transfer for lower limb reconstruction. Microsurgery 31:205–211. doi:10.1002/micr.20841
Bilic R et al (2006) Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis. Int Orthop 30:128–134. doi:10.1007/s00264-005-0045-z
Blum AL, BongioVanni JC, Morgan SJ, Flierl MA, dos Reis FB (2010) Complications associated with distraction osteogenesis for infected nonunion of the femoral shaft in the presence of a bone defect: a retrospective series. J Bone Jt Surg Br 92:565–570. doi:10.1302/0301-620X.92B4.23475
Bullens PH, Minderhoud NM, de Waal Malefijt MC, Veth RP, Buma P, Schreuder HW (2009) Survival of massive allografts in segmental oncological bone defect reconstructions. Int Orthop 33:757–760. doi:10.1007/s00264-008-0700-2
Ceruso M, Taddei F, Bigazzi P, Manfrini M (2008) Vascularised fibula graft inlaid in a massive bone allograft: considerations on the bio-mechanical behaviour of the combined graft in segmental bone reconstructions after sarcoma resection. Injury 39(Suppl 3):S68–74. doi:10.1016/j.injury.2008.05.014
Cha JK, Lee JS, Kim MS, Choi SH, Cho KS, Jung UW (2014) Sinus augmentation using BMP-2 in a bovine hydroxyapatite/collagen carrier in dogs. J Clin Periodontol 41:86–93. doi:10.1111/jcpe.12174
Chaddha M, Gulati D, Singh AP, Singh AP, Maini L (2010) Management of massive posttraumatic bone defects in the lower limb with the Ilizarov technique. Acta Orthop Belg 76:811–820
Chakkalakal DA (2005) Alcohol-induced bone loss and deficient bone repair. Alcohol Clin Exp Res 29:2077–2090
Chotel F, Nguiabanda L, Braillon P, Kohler R, Berard J, Abelin-Genevois K (2012) Induced membrane technique for reconstruction after bone tumor resection in children: a preliminary study. Orthop Traumatol Surg Res OTSR 98:301–308. doi:10.1016/j.otsr.2011.11.008
Claes L, Recknagel S, Ignatius A (2012) Fracture healing under healthy and inflammatory conditions Nature reviews. Rheumatology 8:133–143. doi:10.1038/nrrheum.2012.1
Conway JD (2010) Autograft and nonunions: morbidity with intramedullary bone graft versus iliac crest bone graft. Orthop Clin N Am 41:75–84. doi:10.1016/j.ocl.2009.07.006 (table of contents)
Cuthbert RJ, Churchman SM, Tan HB, McGonagle D, Jones E, Giannoudis PV (2013) Induced periosteum a complex cellular scaffold for the treatment of large bone defects. Bone 57:484–492. doi:10.1016/j.bone.2013.08.009
Daftari TK, Whitesides TE Jr, Heller JG, Goodrich AC, McCarey BE, Hutton WC (1994) Nicotine on the revascularization of bone graft. Exp Study Rabbits Spine 19:904–911
de Boer HH, Wood MB (1989) Bone changes in the vascularised fibular graft. J Bone Jt Surg Br 71:374–378
de Boer HH, Wood MB, Hermans J (1990) Reconstruction of large skeletal defects by vascularized fibula transfer. Factors that influenced the outcome of union in 62 cases. Int Orthop 14:121–128
Dimitriou R, Mataliotakis GI, Angoules AG, Kanakaris NK, Giannoudis PV (2011) Complications following autologous bone graft harvesting from the iliac crest and using the RIA: a systematic review. Injury 42(Suppl 2):S3–15. doi:10.1016/j.injury.2011.06.015
Dimitriou R, Tsiridis E, Giannoudis PV (2005) Current concepts of molecular aspects of bone healing. Injury 36:1392–1404. doi:10.1016/j.injury.2005.07.019
Emara KM, Ghafar KA, Al Kersh MA (2011) Methods to shorten the duration of an external fixator in the management of tibial infections. World J Orthop 2:85–92. doi:10.5312/wjo.v2.i9.85
Eward WC, Kontogeorgakos V, Levin LS, Brigman BE (2010) Free vascularized fibular graft reconstruction of large skeletal defects after tumor resection. Clin Orthop Relat Res 468:590–598. doi:10.1007/s11999-009-1053-x
Farfalli GL, Aponte-Tinao L, Lopez-Millan L, Ayerza MA, Muscolo DL (2012) Clinical and functional outcomes of tibial intercalary allografts after tumor resection. Orthopedics 35:e391–396. doi:10.3928/01477447-20120222-25
Foulk DA, Szabo RM (1995) Diaphyseal humerus fractures: natural history and occurrence of nonunion. Orthopedics 18:333–335
Fourman MS, Borst EW, Bogner E, Rozbruch SR, Fragomen AT (2014) Recombinant human BMP-2 increases the incidence and rate of healing in complex ankle arthrodesis. Clin Orthop Relat Res 472:732–739. doi:10.1007/s11999-013-3261-7
Friedlaender GE et al (2001) Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Jt Surg Am 83-A(Suppl 1):S151–S158
Friedrich JB, Moran SL, Bishop AT, Wood CM, Shin AY (2008) Free vascularized fibular graft salvage of complications of long-bone allograft after tumor reconstruction. J Bone Jt Surg Am 90:93–100. doi:10.2106/JBJS.G.00551
Garrison KR et al (2010) Bone morphogenetic protein (BMP) for fracture healing in adults. Cochrane Database Syst Rev. doi:10.1002/14651858.CD006950.pub2
Gaston MS, Simpson AH (2007) Inhibition of fracture healing. J Bone Jt Surg Br 89:1553–1560. doi:10.1302/0301-620X.89B12.19671
Giannoudis PV, Dinopoulos H, Tsiridis E (2005) Bone substitutes: an update. Injury 36(Suppl 3):S20–27. doi:10.1016/j.injury.2005.07.029
Giannoudis PV, Faour O, Goff T, Kanakaris N, Dimitriou R (2011) Masquelet technique for the treatment of bone defects: tips-tricks and future directions. Injury 42:591–598. doi:10.1016/j.injury.2011.03.036
Goel A, Sangwan SS, Siwach RC, Ali AM (2005) Percutaneous bone marrow grafting for the treatment of tibial non-union. Injury 36:203–206. doi:10.1016/j.injury.2004.01.009
Goulet JA, Senunas LE, DeSilva GL, Greenfield ML (1997) Autogenous iliac crest bone graft. Complications and functional assessment. Clin Orthop Relat Res 339:76–81
Gouron R, Deroussen F, Plancq MC, Collet LM (2013) Bone defect reconstruction in children using the induced membrane technique: a series of 14 cases. Orthop Traumatol Surg Res OTSR 99:837–843. doi:10.1016/j.otsr.2013.05.005
Gouron R, Petit L, Boudot C, Six I, Brazier M, Kamel S, Mentaverri R (2014) Osteoclasts and their precursors are present in the induced-membrane during bone reconstruction using the Masquelet technique. J Tissue Eng Regen Med. doi:10.1002/term.1921
Govender S et al (2002) Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Jt Surg Am 84-A:2123–2134
Green SA (1994) Skeletal defects. A comparison of bone grafting and bone transport for segmental skeletal defects. Clin Orthop Relat Res 301:111–117
Haverstock BD, Mandracchia VJ (1998) Cigarette smoking and bone healing: implications in foot and ankle surgery. J Foot Ankle Surg 37:69–74 (discussion 78)
Heitmann C, Erdmann D, Levin LS (2002) Treatment of segmental defects of the humerus with an osteoseptocutaneous fibular transplant. J Bone Jt Surg Am 84-A:2216–2223
Henrich D et al (2013) Establishment and characterization of the Masquelet induced membrane technique in a rat femur critical-sized defect model. J Tissue Eng Regen Med. doi:10.1002/term.1826
Hernandez RK, Do TP, Critchlow CW, Dent RE, Jick SS (2012) Patient-related risk factors for fracture-healing complications in the United Kingdom general practice research database. Acta Orthop 83:653–660. doi:10.3109/17453674.2012.747054
Hernigou P, Mathieu G, Poignard A, Manicom O, Beaujean F, Rouard H (2006) Percutaneous autologous bone-marrow grafting for nonunions. Surgical technique. J Bone Jt Surg Am 88(Suppl 1 Pt 2):322–327. doi:10.2106/JBJS.F.00203
Higgins TF, Casey V, Bachus K (2007) Cortical heat generation using an irrigating/aspirating single-pass reaming vs conventional stepwise reaming. J Orthop Trauma 21:192–197. doi:10.1097/BOT.0b013e318038d952
Houdek MT, Wagner ER, Stans AA, Shin AY, Bishop AT, Sim FH, Moran SL (2016) What is the outcome of allograft and intramedullary free fibula (capanna technique) in pediatric and adolescent patients with bone tumors? Clin Orthop Relat Res 474:660–668. doi:10.1007/s11999-015-4204-2
Huddleston PM, Steckelberg JM, Hanssen AD, Rouse MS, Bolander ME, Patel R (2000) Ciprofloxacin inhibition of experimental fracture healing. J Bone Jt Surg Am 82:161–173
Ja K (1934) The effect of a local calcium depot on osteogenesis and healing of fractures. J Bone Jt Surg Am 16:176–184
Jin HH, Kim DH, Kim TW, Shin KK, Jung JS, Park HC, Yoon SY (2012) In vivo evaluation of porous hydroxyapatite/chitosan-alginate composite scaffolds for bone tissue engineering. Int J Biol Macromol 51:1079–1085. doi:10.1016/j.ijbiomac.2012.08.027
Jun SH, Lee EJ, Jang TS, Kim HE, Jang JH, Koh YH (2013) Bone morphogenic protein-2 (BMP-2) loaded hybrid coating on porous hydroxyapatite scaffolds for bone tissue engineering. J Mater Sci Mater Med 24:773–782. doi:10.1007/s10856-012-4822-0
Kanakaris NK et al (2009) Application of bone morphogenetic proteins to femoral non-unions: a 4-year multicentre experience. Injury 40(Suppl 3):S54–S61. doi:10.1016/S0020-1383(09)70013-0
Kaneda K, Kurakami C, Minami A (1988) Free vascularized fibular strut graft in the treatment of kyphosis. Spine 13:1273–1277
Kang Y, Scully A, Young DA, Kim S, Tsao H, Sen M, Yang Y (2011) Enhanced mechanical performance and biological evaluation of a PLGA coated beta-TCP composite scaffold for load-bearing applications. Eur Polym J 47:1569–1577. doi:10.1016/j.eurpolymj.2011.05.004
Karger C, Kishi T, Schneider L, Fitoussi F, Masquelet AC, French Society of Orthopaedic S, Traumatology (2012) Treatment of posttraumatic bone defects by the induced membrane technique. Orthop Traumatol Surg Res OTSR 98:97–102. doi:10.1016/j.otsr.2011.11.001
Keating JF, Simpson AH, Robinson CM (2005) The management of fractures with bone loss. J Bone Jt Surg Br 87:142–150
Kim DH et al (2009) Prospective study of iliac crest bone graft harvest site pain and morbidity. Spine J 9:886–892. doi:10.1016/j.spinee.2009.05.006
Kline AJ, Gruen GS, Pape HC, Tarkin IS, Irrgang JJ, Wukich DK (2009) Early complications following the operative treatment of pilon fractures with and without diabetes. Foot Ankle Int 30:1042–1047. doi:10.3113/FAI.2009.1042
Kyro A, Usenius JP, Aarnio M, Kunnamo I, Avikainen V (1993) Are smokers a risk group for delayed healing of tibial shaft fractures? Ann Chir Gynaecol 82:254–262
Lee KS, Han SB, Baek JR (2004) Free vascularized osteocutaneous fibular graft to the tibia in 51 consecutive cases. J Reconstr Microsurg 20:277–284. doi:10.1055/s-2004-824884
Li J, Wang Z, Guo Z, Chen GJ, Fu J, Pei GX (2010) The use of allograft shell with intramedullary vascularized fibula graft for intercalary reconstruction after diaphyseal resection for lower extremity bony malignancy. J Surg Oncol 102:368–374. doi:10.1002/jso.21620
Li Z, Ramay HR, Hauch KD, Xiao D, Zhang M (2005) Chitosan-alginate hybrid scaffolds for bone tissue engineering. Biomaterials 26:3919–3928. doi:10.1016/j.biomaterials.2004.09.062
Liang K, Xiang Z, Chen S, Cen S, Zhong G, Yi M, Huang F (2012) Folded free vascularized fibular grafts for the treatment of subtrochanteric fractures complicated with segmental bone defects. J Trauma Acute Care Surg 72:1404–1410. doi:10.1097/TA.0b013e31824473ce
Lin CH, Wei FC, Chen HC, Chuang DC (1999) Outcome comparison in traumatic lower-extremity reconstruction by using various composite vascularized bone transplantation. Plast Reconstr Surg 104:984–992
Ling XF, Peng X (2012) What is the price to pay for a free fibula flap? A systematic review of donor-site morbidity following free fibula flap surgery. Plast Reconstr Surg 129:657–674. doi:10.1097/PRS.0b013e3182402d9a
Liu H, Hu G, Shang P, Shen Y, Nie P, Peng L, Xu H (2013) Histological characteristics of induced membranes in subcutaneous, intramuscular sites and bone defect. Orthop Traumatol Surg Res OTSR 99:959–964. doi:10.1016/j.otsr.2013.08.009
Liu Y, Ming L, Luo H, Liu W, Zhang Y, Liu H, Jin Y (2013) Integration of a calcined bovine bone and BMSC-sheet 3D scaffold and the promotion of bone regeneration in large defects. Biomaterials 34:9998–10006. doi:10.1016/j.biomaterials.2013.09.040
Loder RT (1988) The influence of diabetes mellitus on the healing of closed fractures. Clin Orthop Relat Res 232:210–216
Lowe JA, Della Rocca GJ, Murtha Y, Liporace FA, Stover MD, Nork SE, Crist BD (2010) Complications associated with negative pressure reaming for harvesting autologous bone graft: a case series. J Orthop Trauma 24:46–52. doi:10.1097/BOT.0b013e31819c0ccb
Lyons FG, Gleeson JP, Partap S, Coghlan K, O'Brien FJ (2014) Novel microhydroxyapatite particles in a collagen scaffold: a bioactive bone void filler? Clin Orthop Relat Res 472(4):1318–1328
Maeda M, Bryant MH, Yamagata M, Li G, Earle JD, Chao EY (1988) Effects of irradiation on cortical bone and their time-related changes. A biomechanical and histomorphological study. J Bone Jt Surg Am 70:392–399
Malizos KN, Zalavras CG, Soucacos PN, Beris AE, Urbaniak JR (2004) Free vascularized fibular grafts for reconstruction of skeletal defects. J Am Acad Orthop Surg 12:360–369
Marcacci M, Kon E, Moukhachev V, Lavroukov A, Kutepov S, Quarto R, Mastrogiacomo M, Cancedda R (2007) Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study. Tissue Eng 13(5):947–955
Mariner PD, Wudel JM, Miller DE, Genova EE, Streubel SO, Anseth KS (2013) Synthetic hydrogel scaffold is an effective vehicle for delivery of INFUSE (rhBMP2) to critical-sized calvaria bone defects in rats. J Orthop Res 31:401–406. doi:10.1002/jor.22243
Masquelet AC (2003) Muscle reconstruction in reconstructive surgery: soft tissue repair and long bone reconstruction Langenbeck’s archives of surgery / Deutsche Gesellschaft fur. Chirurgie 388:344–346. doi:10.1007/s00423-003-0379-1
Masquelet AC, Begue T (2010) The concept of induced membrane for reconstruction of long bone defects. Orthop Clin N Am 41:27–37. doi:10.1016/j.ocl.2009.07.011 (table of contents)
Masquelet AC, Fitoussi F, Begue T, Muller GP (2000) Reconstruction of the long bones by the induced membrane and spongy autograft. Ann Chir Plast Esthet 45:346–353
McBride JCM, Banks RE, Taylor D, Ryan J (1993) Healing of segmental bone defects in goat tibia. J Invest Surg 6:369
McCullen SD, Chow AG, Stevens MM (2011) In vivo tissue engineering of musculoskeletal tissues. Curr Opin Biotechnol 22:715–720. doi:10.1016/j.copbio.2011.05.001
Mercado-Pagan AE, Kang Y, Ker DF, Park S, Yao J, Bishop J, Yang Y (2013) Synthesis and characterization of novel elastomeric poly(D, L-lactide urethane) maleate composites for bone tissue engineering. Eur Polym J 49:3337–3349. doi:10.1016/j.eurpolymj.2013.07.004
Mercado-Pagan AE, Stahl AM, Shanjani Y, Yang Y (2015) Vascularization in bone tissue engineering constructs. Ann Biomed Eng 43:718–729. doi:10.1007/s10439-015-1253-3
Minami A, Kasashima T, Iwasaki N, Kato H, Kaneda K (2000) Vascularised fibular grafts. An experience of 102 patients. J Bone Jt Surg Br 82:1022–1025
Muramatsu K, Ihara K, Shigetomi M, Kawai S (2004) Femoral reconstruction by single, folded or double free vascularised fibular grafts. Br J Plast Surg 57:550–555. doi:10.1016/j.bjps.2003.08.021
Muscolo DL (2012) Accurate 3-dimensional preoperative planning and resection in orthopedic oncology. Orthopedics 35:7–8. doi:10.3928/01477447-20111122-01
Muscolo DL, Ayerza MA, Aponte-Tinao LA (2006) Massive allograft use in orthopedic oncology. Orthop Clin N Am 37:65–74. doi:10.1016/j.ocl.2005.08.003
Ng VY (2012) Risk of disease transmission with bone allograft. Orthopedics 35:679–681. doi:10.3928/01477447-20120725-04
Noaman HH (2013) Management of upper limb bone defects using free vascularized osteoseptocutaneous fibular bone graft. Ann Plast Surg 71:503–509. doi:10.1097/SAP.0b013e3182a1aff0
Nusbickel FR, Dell PC, McAndrew MP, Moore MM (1989) Vascularized autografts for reconstruction of skeletal defects following lower extremity trauma. Rev Clin Orthop Relat Res 243:65–70
Ozaksar K, Sugun TS, Toros T, Gurbuz Y, Kayalar M, Ozerkan F (2012) Free vascularized fibular grafts in type 3 open tibia fractures. Acta orthopaedica et traumatologica turcica 46:430–437
Palatnik Y, Rozbruch SR (2011) Femoral reconstruction using external fixation. Adv Orthop 2011:967186. doi:10.4061/2011/967186
Paley D (1990) Problems, obstacles, and complications of limb lengthening by the Ilizarov technique. Clin Orthop Relat Res 250:81–104
Paley D, Catagni M, Argnani F, Prevot J, Bell D, Armstrong P (1992) Treatment of congenital pseudoarthrosis of the tibia using the Ilizarov technique. Clin Orthop Relat Res 250:81–93
Paley D, Herzenberg JE, Paremain G, Bhave A (1997) Femoral lengthening over an intramedullary nail. A matched-case comparison with Ilizarov femoral lengthening. J Bone Jt Surg Am 79:1464–1480
Paley D, Maar DC (2000) Ilizarov bone transport treatment for tibial defects. J Orthop Trauma 14:76–85
Papakostidis C, Bhandari M, Giannoudis PV (2013) Distraction osteogenesis in the treatment of long bone defects of the lower limbs: effectiveness, complications and clinical results; a systematic review and meta-analysis. Bone Jt J 95-B:1673–1680. doi:10.1302/0301-620X.95B12.32385
Pape HC, Zelle BA, Hildebrand F, Giannoudis PV, Krettek C, van Griensven M (2005) Reamed femoral nailing in sheep: does irrigation and aspiration of intramedullary contents alter the systemic response? J Bone Jt Surg Am 87:2515–2522. doi:10.2106/JBJS.D.02024
Patel RA, Wilson RF, Patel PA, Palmer RM (2013) The effect of smoking on bone healing: A systematic review. Bone Jt Res 2:102–111. doi:10.1302/2046-3758.26.2000142
Pelissier P, Bollecker V, Martin D, Baudet J (2002) Foot reconstruction with the “bi-Masquelet” procedure. Ann Chir Plast Esthet 47:304–307
Pelissier P, Masquelet AC, Bareille R, Pelissier SM, Amedee J (2004) Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration. J Orthop Res 22:73–79. doi:10.1016/S0736-0266(03)00165-7
Porter SE, Hanley EN Jr (2001) The musculoskeletal effects of smoking. J Ame Acad Orthop Surg 9:9–17
Qi Y, Sun HT, Fan YG, Li FM, Lin ZS (2016) Do stress fractures induce hypertrophy of the grafted fibula? A report of three cases received free vascularized fibular graft treatment for tibial defects. Chin J Traumatol = Zhonghua chuang shang za zhi / Chin Med Assoc 19:179–181
Quinlan E, Thompson EM, Matsiko A, O'Brien FJ, Lopez-Noriega A (2015) Long-term controlled delivery of rhBMP-2 from collagen-hydroxyapatite scaffolds for superior bone tissue regeneration. J Control Release 207:112–119
Qvick LM, Ritter CA, Mutty CE, Rohrbacher BJ, Buyea CM, Anders MJ (2013) Donor site morbidity with reamer-irrigator-aspirator (RIA) use for autogenous bone graft harvesting in a single centre 204 case series. Injury 44:1263–1269. doi:10.1016/j.injury.2013.06.008
Rabitsch K, Maurer-Ertl W, Pirker-Fruhauf U, Wibmer C, Leithner A (2013) Intercalary reconstructions with vascularised fibula and allograft after tumour resection in the lower limb. Sarcoma 2013:160295. doi:10.1155/2013/160295
Reichert JC et al (2012) A tissue engineering solution for segmental defect regeneration in load-bearing long bones. Sci Transl Med 4:141ra193. doi:10.1126/scitranslmed.3003720
Repo JP, Sommarhem A, Roine RP, Sintonen H, Halonen T, Tukiainen E (2016) Free vascularized fibular graft is reliable in upper extremity long-bone reconstruction with good long-term outcomes. J Reconstr Microsurg. doi:10.1055/s-0036-1581075
Retzepi M, Donos N (2010) The effect of diabetes mellitus on osseous healing. Clin Oral Implant Res 21:673–681. doi:10.1111/j.1600-0501.2010.01923.x
Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR (2006) Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 27:3413–3431. doi:10.1016/j.biomaterials.2006.01.039
Riebel GD, Boden SD, Whitesides TE, Hutton WC (1995) The effect of nicotine on incorporation of cancellous bone graft in an animal model. Spine 20:2198–2202
Ronga M, Ferraro S, Fagetti A, Cherubino M, Valdatta L, Cherubino P (2014) Masquelet technique for the treatment of a severe acute tibial bone loss. Injury 45(Suppl 6):S111–115. doi:10.1016/j.injury.2014.10.033
Roohani-Esfahani SI, Nouri-Khorasani S, Lu Z, Appleyard R, Zreiqat H (2010) The influence hydroxyapatite nanoparticle shape and size on the properties of biphasic calcium phosphate scaffolds coated with hydroxyapatite-PCL composites. Biomaterials 31:5498–5509. doi:10.1016/j.biomaterials.2010.03.058
Sales de Gauzy J et al (2012) Traumatic diaphyseal bone defects in children. Orthop Traumatol Surg Res OTSR 98:220–226. doi:10.1016/j.otsr.2012.01.001
Schmidmaier G, Herrmann S, Green J, Weber T, Scharfenberger A, Haas NP, Wildemann B (2006) Quantitative assessment of growth factors in reaming aspirate, iliac crest, and platelet preparation. Bone 39:1156–1163. doi:10.1016/j.bone.2006.05.023
Schmitz JP, Hollinger JO (1986) The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res 205:299–308
Scholz AO, Gehrmann S, Glombitza M, Kaufmann RA, Bostelmann R, Flohe S, Windolf J (2015) Reconstruction of septic diaphyseal bone defects with the induced membrane technique. Injury 46(Suppl 4):S121–124. doi:10.1016/S0020-1383(15)30030-9
Seebach C, Henrich D, Kahling C, Wilhelm K, Tami AE, Alini M, Marzi I (2010) 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 16:1961–1970. doi:10.1089/ten.TEA.2009.0715
Shekaran A, Garcia JR, Clark AY, Kavanaugh TE, Lin AS, Guldberg RE, Garcia AJ (2014) Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle. Biomaterials 35:5453–5461. doi:10.1016/j.biomaterials.2014.03.055
Shi Y et al (2016) Evaluation of a novel HA/ZrO2-based porous bioceramic artificial vertebral body combined with a rhBMP-2/chitosan slow-release hydrogel. PLoS ONE 11:e0157698. doi:10.1371/journal.pone.0157698
Song HR, Kale A, Park HB, Koo KH, Chae DJ, Oh CW, Chung DW (2003) Comparison of internal bone transport and vascularized fibular grafting for femoral bone defects. J Orthop Trauma 17:203–211
Soucacos PN, Kokkalis ZT, Piagkou M, Johnson EO (2013) Vascularized bone grafts for the management of skeletal defects in orthopaedic trauma and reconstructive surgery. Injury 44(Suppl 1):S70–75. doi:10.1016/S0020-1383(13)70016-0
Soucacos PN, Korompilias AV, Vekris MD, Zoubos A, Beris AE (2011) The free vascularized fibular graft for bridging large skeletal defects of the upper extremity. Microsurgery 31:190–197. doi:10.1002/micr.20862
Stevenson S (1998) Enhancement of fracture healing with autogenous and allogeneic bone grafts. Clin Orthop Relat Res 355:S239–246
Strong DM et al (1996) Immunologic responses in human recipients of osseous and osteochondral allografts. Clin Orthop Relat Res 326:107–114
Tatara AM, Wong ME, Mikos AG (2014) In vivo bioreactors for mandibular reconstruction. J Dent Res 93:1196–1202. doi:10.1177/0022034514547763
Tierney CM, Haugh MG, Liedl J, Mulcahy F, Hayes B, O’Brien FJ (2009) The effects of collagen concentration and crosslink density on the biological, structural and mechanical properties of collagen-GAG scaffolds for bone tissue engineering. J Mech Behav Biomed Mater 2:202–209. doi:10.1016/j.jmbbm.2008.08.007
Vail TP, Urbaniak JR (1996) Donor-site morbidity with use of vascularized autogenous fibular grafts. J Bone Jt Surg Am 78:204–211
Villa MM, Wang L, Huang J, Rowe DW, Wei M (2015) Bone tissue engineering with a collagen-hydroxyapatite scaffold and culture expanded bone marrow stromal cells. J Biomed Mater Res B Appl Biomater 103(2):243–253
Villemagne T, Bonnard C, Accadbled F, L’Kaissi M, de Billy B, de Gauzy SJ (2011) 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 31:570–576. doi:10.1097/BPO.0b013e31821ffa82
Wong TM, Lau TW, Li X, Fang C, Yeung K, Leung F (2014) Masquelet technique for treatment of posttraumatic bone defects. TheScientificWorldJournal 2014:710302. doi:10.1155/2014/710302
Wood MB, Bishop AT (2007) Massive bone defects of the upper limb: reconstruction by vascularized bone transfer. Hand Clin 23:49–56. doi:10.1016/j.hcl.2007.01.002
Woon CY, Chong KW, Wong MK (2010) Induced membranes—a staged technique of bone-grafting for segmental bone loss: a report of two cases and a literature review. J Bone Jt Surg Am 92:196–201. doi:10.2106/JBJS.I.00273
Yajima H, Tamai S, Mizumoto S, Ono H (1993) Vascularised fibular grafts for reconstruction of the femur. J Bone Jt Surg Br 75:123–128
Zappaterra T et al (2011) Induced membrane technique for the reconstruction of bone defects in upper limb. A prospective single center study of nine cases. Chir Main 30:255–263. doi:10.1016/j.main.2011.06.005
Zhen P, Hu YY, Luo ZJ, Liu XY, Lu H, Li XS (2010) One-stage treatment and reconstruction of Gustilo Type III open tibial shaft fractures with a vascularized fibular osteoseptocutaneous flap graft. J Orthop Trauma 24:745–751. doi:10.1097/BOT.0b013e3181d88a07
Zigdon-Giladi H, Bick T, Lewinson D, Machtei EE (2015) Co-transplantation of endothelial progenitor cells and mesenchymal stem cells promote neovascularization and bone regeneration. Clin Implant Dent Relat Res 17:353–359. doi:10.1111/cid.12104
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Generous support from Kent Thiry and Denise O’Leary, Boswell Foundation, NIH R01AR057837 (NIAMS), and NIH 1U01AR069395 (NIAMS).
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Drs. Roddy, DeBaun, Daoud, and Yang have no conflicts of interest to declare. Dr. Gardner reports personal fees from DePuy-Synthes, personal fees from KCI, personal fees from Miami Medical, personal fees from Biocomposites, personal fees from Pacira, outside the submitted work.
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Roddy, E., DeBaun, M.R., Daoud-Gray, A. et al. Treatment of critical-sized bone defects: clinical and tissue engineering perspectives. Eur J Orthop Surg Traumatol 28, 351–362 (2018). https://doi.org/10.1007/s00590-017-2063-0
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DOI: https://doi.org/10.1007/s00590-017-2063-0