Z Orthop Unfall 2021; 159(03): 304-313
DOI: 10.1055/a-1073-8473
Review

Bone Substitutes in Orthopaedic Surgery: Current Status and Future Perspectives

Knochenersatzmaterialien in der orthopädischen Chirurgie: von der aktuellen Situation zu künftigen Entwicklungen
André Busch
Department of Orthopaedics, Trauma and Reconstructive Surgery, Marienhospital Mülheim an der Ruhr, Chair of Orthopaedics and Trauma Surgery, University of Duisburg-Essen, Germany
,
Alexander Wegner
Department of Orthopaedics, Trauma and Reconstructive Surgery, Marienhospital Mülheim an der Ruhr, Chair of Orthopaedics and Trauma Surgery, University of Duisburg-Essen, Germany
,
Marcel Haversath
Department of Orthopaedics, Trauma and Reconstructive Surgery, Marienhospital Mülheim an der Ruhr, Chair of Orthopaedics and Trauma Surgery, University of Duisburg-Essen, Germany
,
Marcus Jäger
Department of Orthopaedics, Trauma and Reconstructive Surgery, Marienhospital Mülheim an der Ruhr, Chair of Orthopaedics and Trauma Surgery, University of Duisburg-Essen, Germany
› Author Affiliations

Abstract

Bone replacement materials have been successfully supplied for a long time. But there are cases, especially in critical sized bone defects, in which the therapy is not sufficient. Nowadays, there are multiple bone substitutes available. Autologous bone grafts remain the “gold standard” in bone regeneration. Yet, donor-site morbidity and the available amount of sufficient material are limitations for autologous bone grafting. This study aimed to provide information about the current status in research regarding bone substitutes. We report on the advantages and drawbacks of several bone substitutes. At the end, we discuss the current developments of combining ceramic substitutes with osteoinductive substances.

Zusammenfassung

Knochenersatzmaterialien werden seit langem erfolgreich eingesetzt. Jedoch gibt es Fälle, speziell bei Knochendefekten „kritischer“ Größe, bei denen die Therapie nicht erfolgreich ist. Heutzutage steht eine Vielzahl von Knochenersatzmaterialien zur Verfügung. Die autologe Spongiosaplastik stellt immer noch den „Goldstandard“ in der Knochenregeneration dar. Die Morbidität an der Entnahmestelle und die begrenzte Verfügbarkeit an geeignetem Material stellen indes Limitierungen für die Anwendung von autologer Spongiosa dar. Die vorliegende Studie informiert über die aktuelle Situation in der Forschung über Knochenersatzstoffe. Wir berichten über die Vor- und Nachteile von verschiedenen Knochenersatzmaterialien. Zum Schluss diskutieren wir die Möglichkeiten der Kombination von Knochenersatzmaterialien mit osteoinduktiven Substanzen.



Publication History

Article published online:
05 February 2020

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • References

  • 1 Seol YJ, Park JY, Jung JW. et al. Improvement of bone regeneration capability of ceramic scaffolds by accelerated release of their calcium ions. Tissue Eng Part A 2014; 20: 2840-2849 doi:10.1089/ten.TEA.2012.0726
  • 2 Filipowska J, Tomaszewski KA, Niedźwiedzki Ł. et al. The role of vasculature in bone development, regeneration and proper systemic functioning. Angiogenesis 2017; 20: 291-302 doi:10.1007/s10456-017-9541-1
  • 3 Oryan A, Alidadi S, Moshiri A. et al. Bone regenerative medicine: classic options, novel strategies, and future directions. J Orthop Surg Res 2014; 9: 18 doi:10.1186/1749-799X-9-18
  • 4 Simpson AH. The blood supply of the periosteum. J Anat 1985; 140 (Pt. 4): 697-704
  • 5 Florencio-Silva R, Sasso GR, Sasso-Cerri E. et al. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. Biomed Res Int 2015; 2015: 421746 doi:10.1155/2015/421746
  • 6 Herten M, Zilkens C, Thorey F. et al. Biomechanical Stability and Osteogenesis in a Tibial Bone Defect Treated by Autologous Ovine Cord Blood Cells – A Pilot Study. Molecules 2019; 24: pii:E295 doi:10.3390/molecules24020295
  • 7 Li Y, Chen SK, Li L. et al. Bone defect animal models for testing efficacy of bone substitute biomaterials. J Orthop Translat 2015; 3: 95-104
  • 8 Nauth A, McKee MD, Einhorn TA. et al. Managing bone defects. J Orthop Trauma 2011; 25: 462-466
  • 9 Dumic-Cule I, Pecina M, Jelic M. et al. Biological aspects of segmental bone defects management. Int Orthop 2015; 39: 1005-1011
  • 10 Einhorn TA. Enhancement of fracture‐healing. J Bone Joint Surg 1995; 77: 940-956
  • 11 Grgurevic L, Oppermann H, Pecin M. et al. Recombinant Human Bone Morphogenetic Protein 6 Delivered Within Autologous Blood Coagulum Restores Critical Size Segmental Defects of Ulna in Rabbits. JBMR Plus 2018; 3: e10085 doi:10.1002/jbm4.10085
  • 12 Walsh WR, Oliver RA, Christou C. et al. Critical Size Bone Defect Healing Using Collagen-Calcium Phosphate Bone Graft Materials. PLoS One 2017; 12: e0168883 doi:10.1371/journal.pone.0168883
  • 13 Elsalanty ME, Genecov DG. Bone grafts in craniofacial surgery. Craniomaxillofac Trauma Reconstr 2009; 2: 125-134
  • 14 Albrektsson T, Johansson C. Osteoinduction, osteoconduction and osseointegration. Eur Spine J 2001; 10 (Suppl. 02) S96-S101
  • 15 Güven O, Tekin US. Healing of bone defects by an osteopromotion technique using solvent-dehydrated cortical bone plate: a clinical and radiological study. J Craniofac Surg 2006; 17: 1105-1110
  • 16 Jäger M, Jennissen HP, Haversath M. et al. Intrasurgical Protein Layer on Titanium Arthroplasty Explants: From the Big Twelve to the Implant Proteome. Proteomics Clin Appl 2019; 13: e1800168 doi:10.1002/prca.201800168
  • 17 Kraus KH, Kirker-Head C. Mesenchymal stem cells and bone regeneration. Vet Surg 2006; 35: 232-242
  • 18 Baba K, Yamazaki Y, Sone Y. et al. An in vitro long-term study of cryopreserved umbilical cord blood-derived platelet-rich plasma containing growth factors-PDGF-BB, TGF-β, and VEGF. J Craniomaxillofac Surg 2019; 47: 668-675 doi:10.1016/j.jcms.2019.01.020
  • 19 Ong KL, Villarraga ML, Lau E. et al. Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine (Phila Pa 1976) 2010; 35: 1794-1800 doi:10.1097/BRS.0b013e3181ecf6e4
  • 20 Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: an update. Injury 2005; 36 (Suppl. 03) S20-S27
  • 21 Perka C, Schultz O, Spitzer RS. et al. Segmental bone repair by tissue-engineered periosteal cell transplants with bioresorbable fleece and fibrin scaffolds in rabbits. Biomaterials 2000; 21: 1145-1153 doi:10.1016/S0142-9612(99)00280-X
  • 22 Ayukawa Y, Suzuki Y, Tsuru K. et al. Histological Comparison in Rats between Carbonate Apatite Fabricated from Gypsum and Sintered Hydroxyapatite on Bone Remodeling. Biomed Res Int 2015; 2015: 579541 doi:10.1155/2015/579541
  • 23 Wong TM, Lau TW, Li X. et al. Masquelet technique for treatment of posttraumatic bone defects. ScientificWorldJournal 2014; 2014: 710302 doi:10.1155/2014/710302
  • 24 Danti S, Serino LP, DʼAlessandro D. et al. Growing bone tissue-engineered niches with graded osteogenicity: an in vitro method for biomimetic construct assembly. Tissue Eng Part C Methods 2013; 19: 911-924
  • 25 Meeder PJ, Eggers C. The history of autogenous bone grafting. Injury 1994; 25 (Suppl. 01) A2-A3
  • 26 Krause F. Unterkiefer-Plastik. Zentralbl Chir 1907; 34: 1045-1046
  • 27 Payr E. Über osteoplastischen Ersatz nach Kieferresektion (Kieferdefekten) durch Rippenstücke mittels gestielter Brustwandlappen oder freier Transplantation. Zentralbl Chir 1908; 35: 1065-1070
  • 28 France JC, Schuster JM, Moran K. et al. Iliac Crest Bone Graft in Lumbar Fusion: The Effectiveness and Safety Compared with Local Bone Graft, and Graft Site Morbidity Comparing a Single-Incision Midline Approach with a Two-Incision Traditional Approach. Global Spine J 2015; 5: 195-206 doi:10.1055/s-0035-1552985
  • 29 Jäger M, Westhoff B, Wild A. et al. [Bone harvesting from the iliac crest]. Orthopade 2005; 34: 976-982 984, 986–990, 992–994
  • 30 Ivory JP, Thomas IH. Audit of a bone bank. J Bone Joint Surg Br 1993; 75: 355-357
  • 31 Sohn HS, Oh JK. Review of bone graft and bone substitutes with an emphasis on fracture surgeries. Biomater Res 2019; 23: 9 doi:10.1186/s40824-019-0157-y
  • 32 Sutherland AG, Raafat A, Yates P. et al. Infection associated with the use of allograft bone from the north east Scotland Bone Bank. J Hosp Infect 1997; 35: 215-222
  • 33 Behrend C, Carmouche J, Millhouse PW. et al. Allogeneic and Autogenous Bone Grafts Are Affected by Historical Donor Environmental Exposure. Clin Orthop Relat Res 2016; 474: 1405-1409 doi:10.1007/s11999-015-4572-7
  • 34 Feng YF, Wang L, Li X. et al. Influence of architecture of β-tricalcium phosphate scaffolds on biological performance in repairing segmental bone defects. PLoS One 2012; 7: e49955 doi:10.1371/journal.pone.0049955
  • 35 Laschke MW, Strohe A, Scheuer C. et al. In vivo biocompatibility and vascularization of biodegradable porous polyurethane scaffolds for tissue engineering. Acta Biomater 2009; 5: 1991-2001
  • 36 Miron RJ, Zhang YF. Osteoinduction: a review of old concepts with new standards. J Dent Res 2012; 91: 736-744
  • 37 Wang L, Hu YY, Wang Z. et al. Flow perfusion culture of human fetal bone cells in large beta-tricalcium phosphate scaffold with controlled architecture. J Biomed Mater Res A 2009; 91: 102-113
  • 38 Epple M. Biomaterialien und Biomineralisation: Eine Einführung für Naturwissenschaftler, Mediziner und Ingenieure. Wiesbaden: Vieweg + Teubner; 2003
  • 39 Kissling S, Seidenstuecker M, Pilz IH. et al. Sustained release of rhBMP-2 from microporous tricalciumphosphate using hydrogels as a carrier. BMC Biotechnol 2016; 16: 44 doi:10.1186/s12896-016-0275-8
  • 40 Campana V, Milano G, Pagano E. et al. Bone substitutes in orthopaedic surgery: from basic science to clinical practice. J Mater Sci Mater Med 2014; 25: 2445-2461 doi:10.1007/s10856-014-5240-2
  • 41 Iaquinta MR, Mazzoni E, Manfrini M. et al. Innovative Biomaterials for Bone Regrowth. Int J Mol Sci 2019; 20: pii:E618 doi:10.3390/ijms20030618
  • 42 Kaur G, Pandey OP, Singh K. et al. A review of bioactive glasses: Their structure, properties, fabrication, and apatite formation. J Biomed Mater Res A 2014; 102: 254-274 doi:10.1002/jbm.a.34690
  • 43 Cannilloa V, Chiellinib F, Fabbri P. et al. Production of Bioglass® 45S5: polycaprolactone composite scaffolds via salt-leaching. Compos Struct 2010; 92: 1823-1832
  • 44 Wu C, Zhang Y, Zhu Y. et al. Structure-property relationships of silk-modified mesoporous bioglass scaffolds. Biomaterials 2010; 31: 3429-3438
  • 45 Xu S, Lin K, Wang Z. et al. Reconstruction of calvarial defect of rabbits using porous calcium silicate bioactive ceramics. Biomaterials 2008; 29: 2588-2596
  • 46 Wu C, Luo Y, Cuniberti G. et al. Three-dimensional printing of hierarchical and tough mesoporous bioactive glass scaffolds with a controllable pore architecture, excellent mechanical strength and mineralization ability. Acta Biomater 2011; 7: 2644-2650
  • 47 Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 2005; 26: 5474-5491
  • 48 Henry JA, Burugapalli K, Neuenschwander P. et al. Structural variants of biodegradable polyesterurethane in vivo evoke a cellular and angiogenic response that is dictated by architecture. Acta Biomater 2009; 5: 29-42 doi:10.1016/j.actbio.2008.08.020
  • 49 Zhang ZY, Teoh SH, Chong MS. et al. Neovascularization and bone formation mediated by fetal mesenchymal stem cell tissue-engineered bone grafts in critical-size femoral defects. Biomaterials 2010; 31: 608-620
  • 50 Mastrogiacomo M1 Scaglione S, Martinetti R. et al. Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics. Biomaterials 2006; 27: 3230-3237
  • 51 Tsuruga E, Takita H, Itoh H. et al. Pore size of porous hydroxyapatite as the cell-substratum controls BMP-induced osteogenesis. J Biochem 1997; 121: 317-324
  • 52 Watanabe S, Takabatake K, Tsujigiwa H. et al. Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area. Int J Med Sci 2016; 13: 466-476 doi:10.7150/ijms.15560
  • 53 Lu JX, Flautre B, Anselme K. et al. Role of interconnections in porous bioceramics on bone recolonization in vitro and in vivo. J Mater Sci Mater Med 1999; 10: 111-120
  • 54 Xiao X, Wang W, Liu D. et al. The promotion of angiogenesis induced by three-dimensional porous beta-tricalcium phosphate scaffold with different interconnection sizes via activation of PI3K/Akt pathways. Sci Rep 2015; 5: 9409 doi:10.1038/srep09409
  • 55 Finkemeier CG. Bone-grafting and bone-graft substitutes. J Bone Joint Surg Am 2002; 84: 454-464
  • 56 Galois L, Mainard D. Bone ingrowth into two porous ceramics with different pore sizes: an experimental study. Acta Orthop Belg 2004; 70: 598-603
  • 57 Galois L, Mainard D, Delagoutte JP. Beta-tricalcium phosphate ceramic as a bone substitute in orthopaedic surgery. Int Orthop 2002; 26: 109-115
  • 58 Koerten HK, van der Meulen J. Degradation of calcium phosphate ceramics. J Biomed Mater Res 1999; 44: 78-86
  • 59 Daculsi G, Passuti N. Effect of the macroporosity for osseous substitution of calcium phosphate ceramics. Biomaterials 1990; 11: 86-87
  • 60 Malhotra A, Habibovic P. Calcium Phosphates and Angiogenesis: Implications and Advances for Bone Regeneration. Trends Biotechnol 2016; 34: 983-992
  • 61 Daculsi G, LeGeros RZ, Heughebaert M. et al. Formation of carbonate-apatite crystals after implantation of calcium-phosphate ceramics. Calcif Tissue Int 1990; 46: 20-27
  • 62 Chazono M, Tanaka T, Komaki H. et al. Bone formation and bioresorption after implantation of injectable beta-tricalcium phosphate granules – hyaluronate complex in rabbit bone defects. J Biomed Mater Res A 2004; 70: 542-549
  • 63 Ishikawa K, Miyamoto Y, Tsuchiya A. et al. Physical and Histological Comparison of Hydroxyapatite, Carbonate Apatite, and β-Tricalcium Phosphate Bone Substitutes. Materials (Basel) 2018; 11: pii:E1993 doi:10.3390/ma11101993
  • 64 Zwingenberger S, Nich C, Valladares RD. et al. Recommendations and considerations for the use of biologics in orthopedic surgery. BioDrugs 2012; 26: 245-256 doi:10.1007/BF03261883
  • 65 Lerner T, Bullmann V, Schulte TL. et al. A level-1 pilot study to evaluate of ultraporous beta-tricalcium phosphate as a graft extender in the posterior correction of adolescent idiopathic scoliosis. Eur Spine J 2009; 18: 170-179
  • 66 Blaha JD. Calcium sulfate bone-void filler. Orthopedics 1998; 21: 1017-1019
  • 67 Beuerlein MJ, McKee MD. Calcium sulfates: what is the evidence?. J Orthop Trauma 2010; 24 (Suppl. 01) 46-51
  • 68 Liodaki E, Kraemer R, Mailaender P. et al. The use of bone graft substitute in hand surgery: a prospective observational study. Medicine (Baltimore) 2016; 95: e3631
  • 69 Urban RM, Turner TM, Hall DJ. et al. Increased bone formation using calcium sulfate-calcium phosphate composite graft. Clin Orthop Relat Res 2007; 459: 110-117
  • 70 Hak DJ. The use of osteoconductive bone graft substitutes in orthopaedic trauma. J Am Acad Orthop Surg 2007; 15: 525-536
  • 71 Kelly CM, Wilkins RM, Gitelis S. et al. The use of a surgical grade calcium sulfate as a bone graft substitute: results of a multicenter trial. Clin Orthop Relat Res 2001; (382) 42-50
  • 72 Bensaïd W, Oudina K, Viateau V. et al. De novo reconstruction of functional bone by tissue engineering in the metatarsal sheep model. Tissue Eng 2005; 11: 814-824 doi:10.1089/ten.2005.11.814
  • 73 Rocha JH, Lemos AF, Agathopoulos S. et al. Scaffolds for bone restoration from cuttlefish. Bone 2005; 37: 850-857 doi:10.1016/j.bone.2005.06.018
  • 74 Chróścicka A, Jaegermann Z, Wychowański P. et al. Synthetic Calcite as a Scaffold for Osteoinductive Bone Substitutes. Ann Biomed Eng 2016; 44: 2145-2157 doi:10.1007/s10439-015-1520-3
  • 75 Yang Y, Yao QQ, Pu XM. et al. Biphasic calcium phosphate macroporous scaffolds derived from oyster shells for bone tissue engineering. Chem Eng J 2011; 173: 837-845 doi:10.1016/j.cej.2011.07.029
  • 76 Dupoirieux L, Pourquier D, Picot MC. et al. Comparative study of three different membranes for guided bone regeneration of rat cranial defects. Int J Oral Maxillofac Surg 2001; 30: 58-62
  • 77 Durmuş E, Celik I, Ozturk A. et al. Evaluation of the potential beneficial effects of ostrich eggshell combined with eggshell membranes in healing of cranial defects in rabbits. J Int Med Res 2003; 31: 223-230
  • 78 Vaid C, Murugavel S. Alkali oxide containing mesoporous bioactive glasses: synthesis, characterization and in vitro bioactivity. Mater Sci Eng C Mater Biol Appl 2013; 33: 959-968
  • 79 Lu JX, Wei J, Gan Q. et al. Preparation, bioactivity, degradability and primary cell responses to an ordered mesoporous magnesium–calcium silicate. Microporous Mesoporous Mater 2012; 163: 221-228 doi:10.1016/j.micromeso.2012.06.037
  • 80 Thrivikraman G, Athirasala A, Twohig C. et al. Biomaterials for Craniofacial Bone Regeneration. Dent Clin North Am 2017; 61: 835-856 doi:10.1016/j.cden.2017.06.003
  • 81 Gerhardt LC, Boccaccini AR. Bioactive Glass and Glass-Ceramic Scaffolds for Bone Tissue Engineering. Materials (Basel) 2010; 3: 3867-3910
  • 82 Shadanbaz S, Dias GJ. Calcium phosphate coatings on magnesium alloys for biomedical applications: a review. Acta Biomater 2012; 8: 20-30
  • 83 Liu C, Ren Z, Xu YD. et al. Biodegradable Magnesium Alloys Developed as Bone Repair Materials: A Review. Scanning 2018; 2018: 9216314 doi:10.1155/2018/9216314
  • 84 Yoshizawa S, Brown A, Barchowsky A. et al. Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation. Acta Biomater 2014; 10: 2834-2842
  • 85 Tamimi F, Le Nihouannen D, Bassett DC. et al. Biocompatibility of magnesium phosphate minerals and their stability under physiological conditions. Acta Biomater 2011; 7: 2678-2685
  • 86 Waizy H, Seitz JM, Reifenrath J. et al. Biodegradable magnesium implants for orthopedic applications. J Mater Sci 2013; 48: 39-50 doi:10.1007/s10853-012-6572-2
  • 87 Brar HS, Wong J, Manuel MV. Investigation of the mechanical and degradation properties of Mg-Sr and Mg-Zn-Sr alloys for use as potential biodegradable implant materials. J Mech Behav Biomed Mater 2012; 7: 87-95
  • 88 Kim YK, Lee KB, Kim SY. et al. Gas formation and biological effects of biodegradable magnesium in a preclinical and clinical observation. Sci Technol Adv Mater 2018; 19: 324-335 doi:10.1080/14686996.2018.1451717
  • 89 Sezer N, Evis Z, Said MK. et al. Review of magnesium-based biomaterials and their applications. J Magnes Alloy 2018; 6: 23-43
  • 90 Witte F, Hort N, Vogt C. et al. Degradable biomaterials based on magnesium corrosion. Curr Opin Solid State Mater Sci 2008; 12: 63-72 doi:10.1016/j.cossms.2009.04.001
  • 91 Friedman CD, Costantino PD, Takagi S. et al. BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction. J Biomed Mater Res 1998; 43: 428-432
  • 92 Siddiqui HA, Pickering KL, Mucalo MR. A Review on the Use of Hydroxyapatite-Carbonaceous Structure Composites in Bone Replacement Materials for Strengthening Purposes. Materials (Basel) 2018; 11: pii:E1813 doi:10.3390/ma11101813
  • 93 Wong DA, Kumar A, Jatana S. et al. Neurologic impairment from ectopic bone in the lumbar canal: a potential complication of off-label PLIF/TLIF use of bone morphogenetic protein-2 (BMP-2). Spine J 2008; 8: 1011-1018
  • 94 Smucker JD, Rhee JM, Singh K. et al. Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine. Spine (Phila Pa 1976) 2006; 31: 2813-2819
  • 95 Kempen DH, Lu L, Heijink A. et al. Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials 2009; 30: 2816-2825
  • 96 Lee DD, Kim JY. A comparison of radiographic and clinical outcomes of anterior lumbar interbody fusion performed with either a cellular bone allograft containing multipotent adult progenitor cells or recombinant human bone morphogenetic protein-2. J Orthop Surg Res 2017; 12: 126 doi:10.1186/s13018-017-0618-8
  • 97 Burkus JK, Dryer RF, Arnold PM. et al. Clinical and Radiographic Outcomes in Patients Undergoing Single-level Anterior Cervical Arthrodesis: A Prospective Trial Comparing Allograft to a Reduced Dose of rhBMP-2. Clin Spine Surg 2017; 30: E1321-E1332 doi:10.1097/BSD.0000000000000409
  • 98 Dou X, Wang Y, He J. et al. R.T.R® promotes bone marrow mesenchymal stem cells osteogenic differentiation by upregulating BMPs/SMAD induced cbfa1 expression. Dent Mater J 2019; 38: 764-770 doi:10.4012/dmj.2018-306
  • 99 Lehman LFC, de Noronha MS, Diniz IMA. et al. Bioactive glass containing 90 % SiO2 in hard tissue engineering: An in vitro and in vivo characterization study. J Tissue Eng Regen Med 2019; 13: 1651-1663 doi:10.1002/term.2919
  • 100 Othman Z, Fernandes H, Groot AJ. et al. The role of ENPP1/PC-1 in osteoinduction by calcium phosphate ceramics. Biomaterials 2019; 210: 12-24 doi:10.1016/j.biomaterials.2019.04.021
  • 101 Ono N, Kronenberg HM. Bone repair and stem cells. Curr Opin Genet Dev 2016; 40: 103-107 doi:10.1016/j.gde.2016.06.012
  • 102 Asahara T, Masuda H, Takahashi T. et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85: 221-228 doi:10.1161/01.RES.85.3.221
  • 103 Supakul S, Yao K, Ochi H. et al. Pericytes as a Source of Osteogenic Cells in Bone Fracture Healing. Int J Mol Sci 2019; 20: pii:E1079 doi:10.3390/ijms20051079
  • 104 Jackson WM, Aragon AB, Djouad F. et al. Mesenchymal progenitor cells derived from traumatized human muscle. J Tissue Eng Regen Med 2009; 3: 129-138
  • 105 Hadjiargyrou M, OʼKeefe RJ. The convergence of fracture repair and stem cells: interplay of genes, aging, environmental factors and disease. J Bone Miner Res 2014; 29: 2307-2322
  • 106 Deschaseaux F, Sensébé L, Heymann D. Mechanisms of bone repair and regeneration. Trends Mol Med 2009; 15: 417-429
  • 107 Freitas J, Santos SG, Gonçalves RM. et al. Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects. Int J Mol Sci 2019; 20: pii:E3430 doi:10.3390/ijms20143430
  • 108 Dominici M, Le Blanc K, Mueller I. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-317
  • 109 Hendrich C, Franz E, Waertel G. et al. Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients. Orthop Rev (Pavia) 2009; 1: e32 doi:10.4081/or.2009.e32
  • 110 Jäger M, Wild A, Lensing-Höhn S. et al. Influence of different culture solutions on osteoblastic differentiation in cord blood and bone marrow derived progenitor cells. Biomed Tech (Berl) 2003; 48: 241-244
  • 111 Wild A, Jäger M, Lensing-Hoehn S. et al. [Growth behaviour of human mononuclear cells derived from bone marrow and cord blood on a collagen carrier for osteogenic regeneration] [Article in German]. Biomed Tech (Berl) 2004; 49: 227-232
  • 112 Jäger M, Jelinek EM, Wess KM. et al. Bone marrow concentrate: a novel strategy for bone defect treatment. Curr Stem Cell Res Ther 2009; 4: 34-43
  • 113 Jaiswal N, Haynesworth SE, Caplan AI. et al. Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 1997; 64: 295-312
  • 114 Masquelet A, Kanakaris NK, Obert L. et al. Bone Repair Using the Masquelet Technique. J Bone Joint Surg Am 2019; 101: 1024-1036 doi:10.2106/JBJS.18.00842
  • 115 Ziegler CG, Van Sloun R, Gonzalez S. et al. Characterization of Growth Factors, Cytokines, and Chemokines in Bone Marrow Concentrate and Platelet-Rich Plasma: A Prospective Analysis. Am J Sports Med 2019; 47: 2174-2187 doi:10.1177/0363546519832003
  • 116 Seebach C, Henrich D, Kähling C. 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: 1961-1970 doi:10.1089/ten.tea.2009.0715