Treatment of a diaphyseal long-bone defect with autologous bone grafts and platelet-rich plasma in a rabbit model

J. Schneppendahl; P. Jungbluth; T. T. Lögters; M. Sager; M. Wild; M. Hakimi; J. Windolf; J. P. Grassmann

doi:10.3415/VCOT-14-05-0079

Veterinary and Comparative Orthopaedics and Traumatology, Inhaltsverzeichnis

Vet Comp Orthop Traumatol 2015; 28(03): 164-171
DOI: 10.3415/VCOT-14-05-0079

Original Research

Schattauer GmbH

Treatment of a diaphyseal long-bone defect with autologous bone grafts and platelet-rich plasma in a rabbit model

J. Schneppendahl

¹Heinrich Heine University Hospital Düsseldorf, Department of Trauma and Hand Surgery, Düsseldorf, Germany

,

P. Jungbluth

¹Heinrich Heine University Hospital Düsseldorf, Department of Trauma and Hand Surgery, Düsseldorf, Germany

,

T. T. Lögters

¹Heinrich Heine University Hospital Düsseldorf, Department of Trauma and Hand Surgery, Düsseldorf, Germany

,

M. Sager

²Heinrich Heine University Hospital Düsseldorf, Animal Research Institute, Düsseldorf, Germany

,

M. Wild

¹Heinrich Heine University Hospital Düsseldorf, Department of Trauma and Hand Surgery, Düsseldorf, Germany

,

M. Hakimi

¹Heinrich Heine University Hospital Düsseldorf, Department of Trauma and Hand Surgery, Düsseldorf, Germany

,

J. Windolf

¹Heinrich Heine University Hospital Düsseldorf, Department of Trauma and Hand Surgery, Düsseldorf, Germany

,

J. P. Grassmann

¹Heinrich Heine University Hospital Düsseldorf, Department of Trauma and Hand Surgery, Düsseldorf, Germany

› Institutsangaben

Abstract

Summary

Introduction: Large bone defects are a therapeutic challenge to surgeons and are often associated with a high morbidity. The use of autologous cancellous bone graft represents an essential therapeutic option and is considered the gold standard. However, the use of platelet-rich plasma (PRP) for improving bone defect healing has been discussed controversially. The aim of this study was to evaluate the treatment of a diaphyseal long-bone defect in a rabbit model with a combination of PRP and autologous cancellous bone.

Material and methods: A monocortical long-bone defect in the radial diaphysis of 24 New Zealand white rabbits was filled either with autologous cancellous graft as a control group or with autologous cancellous graft combined with autologous PRP. Histomorphometrical and radiological analysis as well as quantification of platelets and growth factors were performed. The animals were euthanatized after three and six weeks according to the study arms.

Results: A significant improvement in bone healing was observed histomorphometrically in the PRP group in the central area of the defect zone (p <0.01) as well as the cortical defect zone (p <0.01). The radiological findings were in accordance with the histomorphometrical results. Comparing native blood and PRP, an enrichment of growth factors and platelets was detectable in the PRP.

Conclusion: Within this animal study, the combination of PRP and autologous cancellous bone grafts improved bone healing significantly compared to the sole application of autologous bone. Therefore, further efforts should be initiated to establish the composite of PRP and autologous bone for bone healing disorders in clinical use.

Keywords

Platelet-rich plasma - diaphysis - bone healing - autologous cancellous bone graft

Volltext

Referenzen

References
1 Audige L, Griffin D, Bhandari M. et al. Path analysis of factors for delayed healing and nonunion in 416 operatively treated tibial shaft fractures. Clin Orthop Relat Res 2005; 438: 221-232.
2 Zimmermann G, Moghaddam A, Wagner C. et al. Klinische Erfahrungen mit Bone Morphogenetic Protein 7 (BMP 7) bei Pseudarthrosen langer Röhrenknochen [Clinical experience with bone morphogenetic protein 7 (BMP 7) in nonunions of long bones]. Unfallchirurg 2006; 109: 528-537.
3 Kanthan SR, Kavitha G, Addi S. et al. Platelet-rich plasma (PRP) enhances bone healing in non-united critical-sized defects: a preliminary study involving rabbit models. Injury 2011; 42: 782-789.
4 Arrington ED, Smith WJ, Chambers HG. et al. Complications of iliac crest bone graft harvesting. Clin Orthop Relat Res 1996; 329: 300-309.
5 Charles M, Barr T, Clokie CM. et al. Fat embolism following posterior iliac graft harvest for jaw reconstruction: managing the complications of major surgery. J Can Dent Assoc 2007; 73: 67-70.
6 Mahendra A, Maclean AD. Available biological treatments for complex non-unions. Injury 2007; 38 Suppl (Suppl. 04) S7-12.
7 Lohmann CH, Andreacchio D, Koster G. et al. Tissue response and osteoinduction of human bone grafts in vivo. Arch Orthop Trauma Surg 2001; 121: 583-590.
8 Pokorny JJ, Davids H, Moneim MS. Vascularized bone graft for scaphoid nonunion. Tech Hand Up Extrem Surg 2003; 7: 32-36.
9 Shafiei Z, Bigham AS, Dehghani SN. et al. Fresh cortical autograft versus fresh cortical allograft effects on experimental bone healing in rabbits: radiological, histopathological and biomechanical evaluation. Cell Tissue Bank 2009; 10: 19-26.
10 Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: an update. Injury 2005; 36 Suppl (Suppl. 03) S20-27.
11 Marx RE, Carlson ER, Eichstaedt RM. et al. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998; 85: 638-646.
12 Bostrom MP, Saleh KJ, Einhorn TA. Osteoinductive growth factors in preclinical fracture and long bone defects models. Orthop Clin North Am 1999; 30: 647-658.
13 Weibrich G, Kleis WK, Hafner G. et al. Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count. J Craniomaxillofac Surg 2002; 30: 97-102.
14 Camargo PM, Lekovic V, Weinlaender M. et al. Platelet-rich plasma and bovine porous bone mineral combined with guided tissue regeneration in the treatment of intrabony defects in humans. J Periodontal Res 2002; 37: 300-306.
15 Dallari D, Savarino L, Stagni C. et al. Enhanced tibial osteotomy healing with use of bone grafts supplemented with platelet gel or platelet gel and bone marrow stromal cells. J Bone Joint Surg Am 2007; 89: 2413-2420.
16 Garg AK. The use of platelet-rich plasma to enhance the success of bone grafts around dental implants. Dent Implantol Update 2000; 11: 17-21.
17 Anitua E, Sanchez M, Orive G. et al. Shedding light in the controversial terminology for platelet rich products. J Biomed Mater Res A 2009; 90: 1262-1263.
18 Malhotra A, Pelletier MH, Yu Y. et al. Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes. Arch Orthop Trauma Surg 2013; 133: 153-165.
19 Kasten P, Vogel J, Geiger F. et al. The effect of platelet-rich plasma on healing in critical-size long-bone defects. Biomaterials 2008; 29: 3983-3992.
20 Grass M, Koppe R, Klotz E. et al. Three-dimensional reconstruction of high contrast objects using C-arm image intensifier projection data. Comput Med Imaging Graph 1999; 23: 311-321.
21 Kropil P, Hakimi AR, Jungbluth P. et al. Cone beam CT in assessment of tibial bone defect healing: an animal study. Acad Radiol 2012; 19: 320-325.
22 Jensen TB, Rahbek O, Overgaard S. et al. Platelet rich plasma and fresh frozen bone allograft as enhancement of implant fixation. An experimental study in dogs. J Orthop Res 2004; 22: 653-658.
23 Roldan JC, Jepsen S, Miller J. et al. Bone formation in the presence of platelet-rich plasma vs. bone morphogenetic protein-7. Bone 2004; 34: 80-90.
24 Aghaloo TL, Moy PK, Freymiller EG. Investigation of platelet-rich plasma in rabbit cranial defects: A pilot study. J Oral Maxillofac Surg 2002; 60: 1176-1181.
25 Weibrich G, Gnoth SH, Otto M. et al. [Growth stimulation of human osteoblast-like cells by thrombocyte concentrates in vitro]. Mund-, Kiefer- und Gesichtschirurgie 2002; 6: 168-174.
26 Lenza M, Ferraz Sde B, Viola DC. et al. Platelet-rich plasma for long bone healing. Einstein (Sao Paulo) 2013; 11: 122-127.
27 Zhang N, Wu YP, Qian SJ. et al. Research progress in the mechanism of effect of PRP in bone deficiency healing. The Scientific World Journal 2013; 134582 http://dx.doi.org/10.1155/2013/134582
28 Schilephake H. Bone growth factors in maxillofacial skeletal reconstruction. Int J Oral Maxillofac Surg 2002; 31: 469-484.
29 Beck LS, DeGuzman L, Lee WP. et al. One systemic administration of transforming growth factor-beta 1 reverses age- or glucocorticoid-impaired wound healing. J Clin Invest 1993; 92: 2841-2849.
30 Galliera E, Corsi MM, Banfi G. Platelet rich plasma therapy: inflammatory molecules involved in tissue healing. J Biol Regul Homeost Agents 2012; 26 2 Suppl (Suppl. 01) 35S-42S.
31 Hakimi M, Jungbluth P, Sager M. et al. Combined use of platelet-rich plasma and autologous bone grafts in the treatment of long bone defects in mini-pigs. Injury 2010; 41: 717-723.
32 Kitoh H, Kitakoji T, Tsuchiya H. et al. Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis--a preliminary result of three cases. Bone 2004; 35: 892-898.
33 Behr B, Tang C, Germann G. et al. Locally applied vascular endothelial growth factor A increases the osteogenic healing capacity of human adipose-derived stem cells by promoting osteogenic and endothelial differentiation. Stem Cells 2011; 29: 286-296.
34 Garrick JG, Riggins RS, Requa RK. et al. Fracture of the mid-shaft of the tibia and fibula. A survey of treatment. Clin Orthop Relat Res 1972; 88: 131-137.
35 Kanakaris NK, Paliobeis C, Nlanidakis N. et al. Biological enhancement of tibial diaphyseal aseptic non-unions: the efficacy of autologous bone grafting, BMPs and reaming by-products. Injury 2007; 38 Suppl (Suppl. 02) S65-75.
36 Triffitt PD, Cieslak CA, Gregg PJ. A quantitative study of the routes of blood flow to the tibial diaphysis after an osteotomy. J Orthop Res 1993; 11: 49-57.
37 Cancedda R, Giannoni P, Mastrogiacomo M. A tissue engineering approach to bone repair in large animal models and in clinical practice. Biomaterials 2007; 28: 4240-4250.