Enhancing bone healing and regeneration: present and future perspectives in veterinary orthopaedics

G. Vertenten; F. Gasthuys; M. Cornelissen; E. Schacht; L. Vlaminck

doi:10.3415/VCOT-09-03-0038

Veterinary and Comparative Orthopaedics and Traumatology, Table of Contents

Vet Comp Orthop Traumatol 2010; 23(03): 153-162
DOI: 10.3415/VCOT-09-03-0038

Review Article

Schattauer GmbH

Enhancing bone healing and regeneration: present and future perspectives in veterinary orthopaedics

Authors

G. Vertenten

¹Department of Surgery and Anaesthesiology of Domestic Animals, Ghent University, Merelbeke, Belgium
F. Gasthuys

¹Department of Surgery and Anaesthesiology of Domestic Animals, Ghent University, Merelbeke, Belgium
M. Cornelissen

²Department of Basic Medical Science, Ghent University, Ghent, Belgium
E. Schacht

³Department of Organic Chemistry, Ghent University, Ghent, Belgium
L. Vlaminck

¹Department of Surgery and Anaesthesiology of Domestic Animals, Ghent University, Merelbeke, Belgium

Abstract

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Summary

Methods currently used to restore bone defects in human and veterinary orthopaedics are often not satisfactory. This is especially the case in the healing of large, irregular defects which result in the formation of tissues with inferior qualities compared to the original structures. For these reasons, several new approaches are currently being explored to improve bone healing capacities in different situations. This review will examine the different techniques used to enhance bone regeneration, highlighting both experimental and clinically applicable methods with regard to veterinary orthopaedics.

Keywords

Bone healing - bone regeneration - orthopaedics - bone tissue engineering - bone grafts

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References

References
1 Brinker WO, Piermattei DL, Flo GL. Small Animal Orthopedics & Fracture Treatment. Philadelphia: WB Saunders Company; 1990
2 Gartner LP, Hiatt JL. Color textbook of histology, vol 2. Philadelphia: WB Saunders Company; 2001
3 Younger EM, Chapman MW. Morbidity at bone graft donor sites. J Orthop Trauma 1989; 3: 192-195.
4 Schwartz CE, Martha JF, Kowalski P. et al. Prospective evaluation of chronic pain associated with posterior autologous iliac crest bone graft harvest and its effect on postoperative outcome. Health Qual Life Outcomes 2009; 7: 49
5 Kanczler JM, Oreffo RO. Osteogenesis and angio-genesis: the potential for engineering bone. Eur Cell Mater 2008; 15: 100-114.
6 Millis DL, Martinez SA. Bone Grafts. In: Slatter D. editor Textbook of Small Animal Surgery Philadelphia: WB Saunders Company; 2003: 1875-1891.
7 Tollefson TT, Senders CW, Sykes JM. Changing perspectives in cleft lip and palate: from acrylic to allele. Arch Facial Plast Surg 2008; 10: 395-400.
8 Legendre L. Maxillofacial fracture repairs. Vet Clin N Am-Small 2005; 35: 985-1008.
9 Callan D. Hard tissue grafting for conventional and implant reconstruction. In: Babbush CA. editor. Dental implants: the art and science. Philadelphia: WB Saunders Company; 2001: 107-123.
10 Bettega G, Brun JP, Boutonnat J. et al. Autologous platelet concentrates for bone graft enhancement in sinus lift procedure. Transfusion 2009; 49: 779-785.
11 Bellows J. Oral surgical equipment, materials and techniques. In: Bellows J. editor Small animal dental equipment, materials & techniques A primer. Victoria, Australia: Blackwell Publishing; 2004: 297-328.
12 Legendre L. Extraction of the lower cuspid, with minimal stress. Can Vet J 1997; 38: 449-450.
13 Marretta SM. Surgical extraction of the mandibular first molar tooth in the dog. J Vet Dent 2002; 19: 46-50.
14 Stevens A, Lowe JS. Pathology. Mosby: Elsevier Health Sciences; 1995
15 Olivier V, Faucheux N, Hardouin P. Biomaterial challenges and approaches to stem cell use in bone reconstructive surgery. Drug Discov Today 2004; 9: 803-811.
16 Arnold JS. A simplified model of wound healing III – The critical size defect in three dimensions. Math Comput Model 2001; 34: 385-392.
17 Chase SW, Herndon CH. The fate of autogenous and homogenous bone grafts – a historical review. J Bone Joint Surg Am 1955; 37: 809-841.
18 Hutchinson J. The fate of experimental bone auto-grafts and homografts. Brit J Surg 1952; 39: 552-561.
19 Schena CJ. The procurement of cancellous bone for grafting in small animal orthopedic-surgery – a review of instrumentation, technique, and patho-physiology. J Am Anim Hosp Assoc 1983; 19: 695-704.
20 Mahendra A, Maclean A. Available biological treatments for complex non-unions. Injury 2007; 38: S7-S12.
21 Blokhuis TJ, Lindner T. Allograft and bone morphogenetic proteins: an overview. Injury 2008; 39: S33-S36.
22 Kao ST, Scott DD. A review of bone substitutes. Oral Maxillofac Surg Clin North Am 2007; 19: 513-521.
23 Hoffer MJ, Griffon DJ, Schaeffer DJ. et al. Clinical applications of demineralized bone matrix: A retrospective and case-matched study of seventy-five dogs. Vet Surg 2008; 37: 639-647.
24 Berglundh T, Lindhe J. Healing around implants placed in bone defects treated with BiO-Oss(R) – An experimental study in the dog. Clin Oral Implant Res 1997; 8: 117-124.
25 Kim IY, Seo SJ, Moon HS. et al. Chitosan and its derivatives for tissue engineering applications. Biotechnol Adv 2008; 26: 1-21.
26 Marcacci M, Kon E, Zaffagnini S. et al. Reconstruction of extensive long-bone defects in sheep using porous hydroxyapatite sponges. Calcified Tissue Int 1999; 64: 83-90.
27 Mastrogiacomo M, Corsi A, Francioso E. et al. Reconstruction of extensive long bone defects in sheep using resorbable bioceramics based on silicon stabilized tricalcium phosphate. Tissue Eng 2006; 12: 1261-1273.
28 Meinig RP. Polylactide membranes in the treatment of segmental diaphyseal defects: Animal model experiments in the rabbit radius, sheep tibia, Yucatan minipig radius, and goat tibia. Injury 2002; 33: 58-65.
29 Teixeira CR, Rahal SC, Volpi RS. et al. Tibial segmental bone defect treated with bone plate and cage filled with either xenogeneic composite or auto-logous cortical bone graft. Vet Comp Orthop Traumatol 2007; 20: 269-276.
30 Saadeh PB, Khosla RK, Mehrara BJ. et al. Repair of a critical size defect in the rat mandible using allogenic type I collagen. J Craniofac Surg 2001; 12: 573-579.
31 Wolff D, Goldberg VM, Stevenson S. Histomorpho-metric Analysis of the repair of a segmental diaphy-seal defect with ceramic and titanium fibermetal implants – effects of bone-marrow. J Orthop Res 1994; 12: 439-446.
32 Johnson KD, Frierson KE, Keller TS. et al. Porous ceramics as bone graft substitutes in long bone defects: A biomechanical, histological, and radio-graphic analysis. J Orthop Res 1996; 14: 351-369.
33 Fujibayashi S, Kim HM, Neo M. et al. Repair of seg-mental long bone defect in rabbit femur using bioactive titanium cylindrical mesh cage. Bio-materials 2003; 24: 3445-3451.
34 Wefer J, Wefer A, Schratt HE. et al. Healing of auto-logous cancellous bone grafts and hydroxylapatite ceramics in tibial segment defects. Unfallchirurg 2000; 103: 452-461.
35 Wheeler DL, Eschbach EJ, Hoellrich RG. et al. Assessment of resorbable bioactive material for grafting of critical-size cancellous defects. J Orthop Res 2000; 18: 140-148.
36 Dorea HC, McLaughlin RM, Cantwell HD. et al. Evaluation of healing in feline femoral defects filled with cancellous autograft, cancellous allograft or Bioglass. Vet Comp Orthop Traumatol 2005; 18: 157-168.
37 Tiedeman JJ, Connolly JF, Strates BS. et al. Treatment of nonunion by percutaneous injection of bone-marrow and demineralized bone-matrix – an experimental-study in dogs. Clin Orthop Rel Res 1991; 268: 294-302.
38 Devine MJ, Mierisch CM, Jang E. et al. Transplanted bone marrow cells localize to fracture callus in a mouse model. J Orthop Res 2002; 20: 1232-1239.
39 Bruder SP, Fink DJ, Caplan AI. Mesenchymal stem-cells in bone-development, bone repair, and skeletal regeneration therapy. J Cell Biochem 1994; 56: 283-294.
40 Tshamala M, van Bree H. Osteoinductive properties of the bone marrow – Myth or reality. Vet Comp Orthop Traumatol 2006; 19: 133-141.
41 Einhorn TA. Enhancement of fracture-healing. J Bone Joint Surg Am 1995; 77: 940-956.
42 Kirkerhead CA. Recombinant bone morphogenetic proteins – novel substances for enhancing bone healing. Vet Surg 1995; 24: 408-419.
43 Simpson A, Mills L, Noble B. The role of growth factors and related agents in accelerating fracture healing. J Bone Joint Surg Br 2006; 88: 701-705.
44 Urist MR. Bone – Formation by autoinduction. Science 1965; 150: 893-899.
45 Urist MR, Mikulski A, Lietze A. Solubilized and insolubilized bone morphogenetic protein. Proc Natl Acad Sci USA 1979; 76: 1828-1832.
46 Helm G, Anderson DG, Andersson GBJ. et al. Summary statement: Bone morphogenetic proteins – Basic science. Spine 2002; 27: S9
47 Schmitt JM, Hwang K, Winn SR. et al. Bone morphogenetic proteins: An update on basic biology and clinical relevance. J Orthop Res 1999; 17: 269-278.
48 Cheng HW, Jiang W, Phillips FM. et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 2003; 85: 1544-1552.
49 Nakase T, Nomura S, Yoshikawa H. et al. Transient and localized expression of bone morphogenetic protein-4 messenger-RNA during fracture-healing. J Bone Miner Res 1994; 9: 651-659.
50 Yoshimura Y, Nomura S, Kawasaki S. et al. Colocalization of noggin and bone morphogenetic protein-4 during fracture healing. J Bone Miner Res 2001; 16: 876-884.
51 Yasko AW, Lane JM, Fellinger EJ. et al. The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (Rhbmp-2) – a radiographic, histological, and biomechanical study in rats. J Bone Joint Surg Am 1992; 74: 659-670.
52 Kirkerhead CA, Gerhart TN, Schelling SH. et al. Long-term healing of bone using recombinant human bone morphogenetic protein-2. Clin Orthop Rel Res 1995; 318: 222-230.
53 Zegzula HD, Buck DC, Brekke J. et al. Bone formation with use of rhBMP-2 – (Recombinant human bone morphogenetic protein-2). J Bone Joint Surg Am 1997; 79: 1778-1790.
54 Sciadini MF, Johnson KD. Evaluation of recombinant human bone morphogenetic protein-2 as a bone-graft substitute in a canine segmental defect model. J Orthop Res 2000; 18: 289-302.
55 Niyibizi C, Baltzer A, Lattermann C. et al. Potential role for gene therapy in the enhancement of fracture healing. Clin Orthop Relat Res 1998; 355: S148-153.
56 Southwood LL, Frisbie DD, Kawcak CE. et al. Delivery of growth factors using gene therapy to enhance bone healing. Vet Surg 2004; 33: 565-578.
57 Betz OB, Betz VM, Nazarian A. et al. Direct percutaneous gene delivery to enhance healing of segmental bone defects. J Bone Joint Surg Am 2006; 88: 355-365.
58 Zachos T, Diggs A, Weisbrode S. et al. Mesenchymal stem cell-mediated gene delivery of bone morpho-genetic protein-2 in an articular fracture model. Mol Ther 2007; 15: 1543-1550.
59 Bishop GB, Einhorn TA. Current and future clinical applications of bone morphogenetic proteins in orthopaedic trauma surgery. Int Orthop 2007; 31: 721-727.
60 McKay WF, Peckham SM, Badura JM. A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft). Int Orthop 2007; 31: 729-734.
61 Kirker-Head CA, Boudrieau RJ, Kraus KH. Use of bone morphogenetic proteins for augmentation of bone regeneration. J Am Vet Med Assoc 2007; 231: 1039-1055.
62 Jackson IT, Scheker LR, Vandervord JG. et al. Bone-marrow grafting in the secondary closure of alveolar-palatal defects in children. Br J Plast Surg 1981; 34: 422-425.
63 Lindholm TS, Urist MR. A quantitative analysis of new bone formation by induction in compositive grafts of bone marrow and bone matrix. Clin Orthop Rel Res 1980; 150: 288-300.
64 Green E, Hinton C, Triffitt JT. The effect of decalcified bone matrix on the osteogenic potential of bone marrow. Clin Orthop Rel Res 1986; 205: 292-298.
65 Ohgushi H, Goldberg VM, Caplan AI. Repair of bone defects with marrow-cells and porous ceramic – experiments in rats. Acta Orthop Scand 1989; 60: 334-339.
66 Connolly JF, Guse R, Tiedeman J. et al. Autologous marrow injection as a substitute for operative grafting of tibial nonunions. Clin Orthop Rel Res 1991; 266: 259-270.
67 Salgado AJ, Oliveira JT, Pedro AJ. et al. Adult stem cells in bone and cartilage tissue engineering. Curr Stem Cell Res Ther 2006; 1: 345-364.
68 Kadiyala S, Jaiswal N, Bruder SP. Culture-expanded, bone marrow-derived mesenchymal stem cells can regenerate a critical-sized segmental bone defect. Tissue Eng 1997; 3: 173-185.
69 Krebsbach PH, Mankani MH, Satomura K. et al. Repair of craniotomy defects using bone marrow stromal cells. Transplantation 1998; 66: 1272-1278.
70 Bruder SP, Kraus KH, Goldberg VM. et al. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg Am 1998; Jul 80: 985-996.
71 Kon E, Muraglia A, Corsi A. et al. Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res 2000; 49: 328-337.
72 Barralet J, Gbureck U, Habibovic P. et al. Angiogenesis in calcium phosphate scaffolds by inorganic copper ion release. Tissue Eng Part A 2009
73 Yasuda I. Classic fundamental aspects of fracture treatment. Clin Orthop Rel Res 1977; 124: 5-8.
74 Briggs KK, Martinez SA, Smith LV. et al. Comparison of the osteogenic effects between two surface interferential stimulation devices to enhance surgically based spinal fusion. Vet Comp Orthop Traumatol 2004; 17: 41-47.
75 Nawrocki MA, Martinez SA, Hughes J. et al. Augmentation of intertransverse process lumbar fusion. Vet Comp Orthop Traumatol 2006; 19: 72-80.
76 Ducharme NG, Nixon AJ. Delayed Union, Nonunion, and Malunion. In: Nixon AJ. editor Equine Fracture Repair. Philadelphia: Saunders; 1996: 354-358.
77 Schaden W, Fischer A, Sailler A. Extracorporeal shock wave therapy of nonunion or delayed osseous union. Clin Orthop Rel Res 2001; 387: 90-94.
78 Ciampa AR, de Prati AC, Amelio E. et al. Nitric oxide mediates anti-inflammatory action of extra-corporeal shock waves. Febs Lett 2005; 579: 6839-6845.
79 Olds RB. Autogenous cancellous bone grafting in small animals. J Am Anim Hosp Assoc 1973; 9: 430-435.
80 Schwarz N, Schlag G, Thurnher M. et al. Fresh autogeneic, frozen allogeneic, and decalcified allogeneic bone-grafts in dogs. J Bone Joint Surg Br 1991; 73: 787-790.
81 Dowdle SM, Spotswood TC, Lambrechts NE. et al. Aneurysmal bone cyst in the distal radius of a dog: diagnostic imaging and surgical treatment. Vet Comp Orthop Traumatol 2003; 16: 116-121.
82 Duval JM, Chambers JN, Newell SM. Surgical-treatment of an aneurysmal bone-cyst in a dog. Vet Comp Orthop Traumatol 1995; 8: 213-217.
83 Kim CS, Choi SH, Cho KS. et al. Periodontal healing in one-wall intra-bony defects in dogs following implantation of autogenous bone or a coral-derived biomaterial. J Clin Periodontol 2005; 32: 583-589.
84 Voss K, Steffen F, Montavon PM. Use of the ComPact UniLock System for ventral stabilization procedures of the cervical spine – A retrospective study. Vet Comp Orthop Traumatol 2006; 19: 21-28.
85 Ozak A, Besalti O, Pekcan Z. et al. Ventral fixation in atlantoaxial instability with axial fracture in a dog. Vet Comp Orthop Traumatol 2006; 19: 57-59.
86 Shani J, Yeshurun Y, Shahar R. Arthrodesis of the tarsometatarsal joint, using type II ESF with acrylic connecting bars in dour dogs. Vet Comp Orthop Traumatol 2006; 19: 61-63.
87 Johnson KA, Bellenger CR. The effects of auto-logous bone-grafting on bone healing after carpal arthrodesis in the dog. Vet Rec 1980; 107: 126-132.
88 Kerwin SC, Lewis DD, Elkins AD. et al. Deep-frozen allogeneic cancellous bone grafts in 10 dogs: A case series. Vet Surg 1996; 25: 18-28.
89 Heiple KG, Goldberg VM, Powell AE. et al. Biology of cancellous bone-grafts. Orthop Clin North Am 1987; 18: 179-185.
90 Fitch R, Kerwin S, Sinibaldi KR. et al. Bone auto-grafts and allografts in dogs. Compend Contin Educ Pract Vet 1997; 19: 558-578.
91 Liptak JM, Dernell WS, Ehrhart N. et al. Cortical allograft and endoprosthesis for limb-sparing surgery in dogs with distal radial osteosarcoma: A prospective clinical comparison of two different limb-sparing techniques. Vet Surg 2006; 35: 518-533.
92 Sinibaldi KR. Evaluation of full cortical allografts in 25 dogs. J Am Vet Med Assoc 1989; 194: 1570-1577.
93 Boudrieau RJ, Tidwell AS, Ullman SL. et al. Correction of mandibular nonunion and malocculsion by plate fixation and autogenous cortical bone-grafts in 2 dogs. J Am Vet Med Assoc 1994; 204: 744-750.
94 Ishikawa Y, Goris RC, Nagaoka K. Use of a corticocancellous bone-graft in the repair of a cleft-palate in a dog. Vet Surg 1994; 23: 201-205.
95 Hildreth BE, Johnson KA. Ulnocarpal arthrodesis for the treatment of radial agenesis in a dog. Vet Comp Orthop Traumatol 2007; 20: 231-235.
96 Liptak JM, Edwards MR, James SP. et al. Biomechanical characteristics of allogeneic cortical bone pins designed for fracture fixation. Vet Comp Orthop Traumatol 2008; 21: 140-146.
97 Worth AJ, Thompson KG, Owen MC. et al. Combined xeno/auto-grafting of a benign osteolytic lesion in a dog, using a novel bovine cancellous bone biomaterial. N Z Vet J 2007; 55: 143-148.
98 Toombs JP, Wallace LJ. Evaluation of autogeneic and allogeneic cortical chip grafting in a feline tibial nonunion model. Am J Vet Res 1985; 46: 519-528.
99 Frenkel SR, Moskovich R, Spivak J. et al. Demineralized bone matrix. Enhancement of spinal fusion. Spine 1993; 18: 1634-1639.
100 Fuller DA, Stevenson S, Emery SE. The effects of internal fixation on calcium carbonate – Ceramic anterior spinal fusion in dogs. Spine 1996; 21: 2131-2136.
101 Gauthier O, Boix D, Grimandi G. et al. A new injectable calcium phosphate biomaterial for immediate bone filling of extraction sockets: A preliminary study in dogs. J Periodontol 1999; 70: 375-383.
102 Damron TA. Use of 3D beta-tricalcium phosphate (Vitoss (R)) scaffolds in repairing bone defects. Nanomedicine 2007; 2: 763-775.
103 Gauthier O, Izembart A, Goyenvalle E. et al. The use of a synthetic bone substitute in the surgical treatment of a dental tumour in a dog. Prat Med Chir Anim 2000; 35: 123-130.
104 Hauschild G, Bader A, Uhr G. et al. Clinical use of tricalciumphosphate – experience with a matrix-based approach to osseous regeneration. Tieraerztl Prax 2007; 35: 5-13.
105 Dorea FA, Padilha JG, Santos LA. et al. The use of hydroxyapatite for arthrodesis in dogs and cats: a clinical study. Arq Bras Med Vet Zoo 2007; 59: 932-938.
106 Franch J, Diaz-Bertrana C, Lafuente P. et al. Beta-tricalcium phosphate as a synthetic cancellous bone graft in veterinary orthopaedics – A retrospective study of 13 clinical cases. Vet Comp Orthop Traumatol 2006; 19: 196-204.
107 Oktar FN, Ozsoy S, Altintas S. A practical method for clinical veterinary use: Use of dentine hydroxyapatite (DHA) as a graft material. Key Eng Mat 2006; 309 (311) 1387-1390.
108 Legendre L. Extraction of the upper cuspid, without stress. Can Vet J 1996; 37: 692-694.
109 Grundel RE, Chapman MW, Yee T. et al. Autogeneic bone-marrow and porous biphasic calcium-phosphate ceramic for segmental bone defects in the canine ulna. Clin Orthop Rel Res 1991; 266: 244-258.
110 Malard O, Guicheux J, Bouler JM. et al. Calcium phosphate scaffold and bone marrow for bone reconstruction in irradiated area: a dog study. Bone 2005; 36: 323-330.
111 Zamprogno H, Lopez PCM, Oliveira ALA. et al. The use of bone marrow stromal cells to treat bone defects in dogs. 14^th ESVOT Congress: 10-14 September 2008. Munich; Germany:
112 Itoh T, Mochizuki M, Fuda K. et al. Femoral nonunion fracture treated with recombinant human bone morphogenetic protein-2 in a dog. J Vet Med Sci 1998; 60: 535-538.
113 Schmokel HG, Weber FE, Seiler G. et al. Treatment of nonunions with nonglycosylated recombinant human bone morphogenetic protein-2 delivered from a fibrin matrix. Vet Surg 2004; 33: 112-118.
114 Milovancev M, Muir P, Manley PA. et al. Clinical application of recombinant human bone morpho-genetic protein-2 in 4 dogs. Vet Surg 2007; 36: 132-140.
115 Bernard F, Furneaux R, Da Silva CA. et al. Treatment with rhBMP-2 of extreme radial bone atrophy secondary to fracture management in an Italian Greyhound. Vet Comp Orthop Traumatol 2008; 21: 64-68.
116 Boudrieau RJ, Mitchell SL, Seeherman H. Mandibular reconstruction of a partial hemimandibulectomy in a dog with severe malocclusion. Vet Surg 2004; 33: 119-130.
117 Lewis JR, Boudrieau RJ, Reiter AM. et al. Mandibular reconstruction after gunshot trauma in a dog by use of recombinant human bone morphogenetic protein-2. J Am Vet Med Assoc 2008; 233: 1598-1604.
118 Spector DI, Keating JH, Boudrieau RJ. Immediate mandibular reconstruction of a 5 cm defect using rhBMP-2 after partial mandibulectomy in a dog. Vet Surg 2007; 36: 752-759.
119 Kraus KH, Kirker-Head C. Mesenchymal stem cells and bone regeneration. Vet Surg 2006; 35: 232-242.
120 Clark DM. The use of electrical-current in the treatment of nonunions. Vet Clin N Am-Small 1987; 17: 793-798.
121 Danova NA, Muir P. Extracorporeal shock wave therapy for supraspinatus calcifying tendinopathy in two dogs. Vet Rec 2003; 152: 208-209.
122 Pearce AI, Richards RG, Milz S. et al. Animal models for implant biomaterial research in bone: A review. Eur Cell Mater 2007; 13: 1-10.
123 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.
124 Vlaminck L, Gorski T, Huys L. et al. Immediate postextraction implant placement in sheep's mandibles: A pilot study. Implant Dent 2008; 17: 439-450.
125 Chim H, Gosain AK. Biomaterials in craniofacial surgery: experimental studies and clinical application. J Craniofac Surg 2009; 20: 29-33.
126 Nolff MC, Gellrich NC, Hauschild G. et al. Comparison of two beta-tricalcium phosphate composite grafts used for reconstruction of mandibular critical size bone defects. Vet Comp Orthop Traumatol 2009; 22: 96-102.
127 Kobayashi H, Fujishiro T, Belkoff SM. et al. Long-term evaluation of a calcium phosphate bone cement with carboxymethyl cellulose in a vertebral defect model. J Biomed Mater Res Part A 2009; 88: 880-888.
128 Takahata M, Kotani Y, Abumi K. et al. An investigational study on the healing process of anterior spinal arthrodesis using a bioactive ceramic spacer and the change in load-sharing of spinal instrumentation. Spine 2005; 30: E195-E203.
129 Kasari TR, Taylor TS, Baird AN. et al. Use of autogenous cancellous bone-graft for treatment of osteolytic defects in the phalanges of 3 cattle. J Am Vet Med Assoc 1992; 201: 1053-1057.
130 Barneveld A. Cancellous bone grafting in the treatment of bovine septic physitis. Vet Q 1994; 16 (Suppl. 02) S104-S107.
131 Henninger RW, Bramlage LR, Schneider RK. et al. Lag screw and cancellous bone-graft fixation of transverse proximal sesamoid bone-fractures in horses – 25 cases (1983–1989). J Am Vet Med Assoc 1991; 199: 606-612.
132 Kold SE, Hickman J. Use of an autogenous cancellous bone-graft in the treatment of subchondral bone-cysts in the medial femoral condyle of the horse. Equine Vet J 1983; 15: 312-316.
133 Honnas CM, Crabill MR, Mackie JT. et al. Use of autogenous cancellous bone-grafting in the treatment of septic navicular bursitis and distal sesamoid osteomyelitis in horses. J Am Vet Med Assoc 1995; 206: 1191-1194.
134 Lescun TB, Morisset SM, Fugaro MN. et al. Facilitated ankylosis of the distal interphalangeal joint in a foal. Aust Vet J 2004; 82: 282-285.
135 Archer RM, Schneider RK, Lindsay WA. et al. Arthrodesis of the equine distal tarsal joints by perforated stainless steel cylinders. Equine Vet J Suppl 1988; 6: 125-130.
136 Richardson DW, Nunamaker DM, Sigafoos RD. Use of an external skeletal fixation device and bone graft for arthrodesis of the metacarpophalangeal joint in horses. J Am Vet Med Assoc 1987; 191: 316-321.
137 Zubrod CJ, Schneider RK. Arthrodesis techniques in horses. Vet Clin N Am-Equine 2005; 21: 691-711.
138 Bertone AL, Schneiter HL, Turner AS. et al. Pancarpal arthrodesis for treatment of carpal collapse in the adult horse – a report of 2 cases. Vet Surg 1989; 18: 353-359.
139 Jackson WA, Stick JA, Arnoczky SP. et al. The effect of compacted cancellous bone grafting on the healing of subchondral bone defects of the medial femoral condyle in horses. Vet Surg 2000; 29: 8-16.
140 DeBowes RM, Grant BD, Bagby GW. et al. Cervical vertebral interbody fusion in the horse: a comparative study of bovine xenografts and autografts supported by stainless steel baskets. Am J Vet Res 1984; 45: 191-199.
141 Kirkerhead CA. Novel Biological Agents to Enhance Fracture Healing. In: Nixon AJ. editor Equine Fracture Repair Philadelphia: Saunders; 1996: 93-103.
142 Schumacher J, Brink P, Easley J. et al. Surgical correction of wry nose in four horses. Vet Surg 2008; 37: 142-148.
143 Jackman BR, Baxter GM. Treatment of a mandibular bone-cyst by use of a corticocancellous bone-graft in a horse. J Am Vet Med Assoc 1992; 201: 892-894.
144 Markel MD. Bone Grafts and Bone Substitutes. In: Nixon AJ. editor. Equine Fracture Repair. Philadelphia: Saunders; 1996: 87-92.
145 Cassotis NJ, Stick JA, Arnoczky SP. Use of full cortical allograft to repair a metatarsal fracture in a foal. J Am Vet Med Assoc 1997; 211: 1155-1157.
146 Rose PL, Auer JA, Hulse D. et al. Effect of beta-tricalcium phosphate in surgically created subchondral bone defects in male horses. Am J Vet Res 1988; 49: 417-424.
147 Vidal MA, Kilroy GE, Johnson JR. et al. Cell growth characteristics and differentiation frequency of adherent equine bone marrow-derived mesenchymal stromal cells: Adipogenic and osteogenic capacity. Vet Surg 2006; 35: 601-610.
148 Vidal MA, Kilroy GE, Lopez MJ. et al. Characterization of equine adipose tissue-derived stromal cells: Adipogenic and osteogenic capacity and comparison with bone marrow-derived mesenchymal stromal cells. Vet Surg 2007; 36: 613-622.
149 Koch TG, Berg LC, Betts DH. Concepts for the clinical use of stem cells in equine medicine. Can Vet J-Rev Vet Can 2008; 49: 1009-1017.
150 Perrier M, Lu Y, Nemke B. et al. Acceleration of second and fourth metatarsal fracture healing with recombinant human bone morphogenetic protein-2/calcium phosphate cement in horses. Vet Surg 2008; 37: 648-655.
151 Ishihara A, Shields KM, Litsky AS. et al. Osteogenic gene regulation and relative acceleration of healing by adenoviral/mediated transfer of human BMP-2 or-6 in equine osteotomy and ostectomy models. J Orthop Res 2008; 26: 764-771.
152 Ishihara A, Zachos TA, Bartlett JS. et al. Evaluation of permissiveness and cytotoxic effects in equine chondrocytes, synovial cells, and stem cells in response to infection with adenovirus 5 vectors for gene delivery. Am J Vet Res 2006; 67: 1145-1155.
153 Lippold BS, Schmoekel HG, Weber FE. et al. The use of nonglycosylated recombinant human bone morphogenic protein 2 (rhBMP-2) released from a fibrin matrix to promote arthrodesis in an equine pastern joint. Pferdeheilkunde 2004; 20: 442-446.
154 Bramlage LR, Weisbrode SM, Spurlock GE. The effect of a pulsating electromagnetic-field on cortical bone healing and bone remodeling of the equine metacarpus. Vet Surg 1985; 14: 49
155 Collier MA, Kallfelz FA, Rendano VT. et al. Capacitively coupled electrical-stimulation of bone healing in the horse – invivo study with a Salter type-IV osteotomy model with stainless-steel surface electrodes. Am J Vet Res 1985; 46: 623-631.
156 Collier MA, Brighton CT, Norrdin R. et al. Direct-current stimulation of bone production in the horse – preliminary-study with a gap healing model. Am J Vet Res 1985; 46: 610-621.
157 McClure SA, Merritt DK. Extracorporeal shock-wave therapy for equine musculoskeletal disorders. Compend Contin Educ Pract Vet 2003; 25: 68-75.
158 Bruder SP, Kurth AA, Shea M. et al. Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells. J Orthop Res 1998; 16: 155-62.
159 Arinzeh TL, Peter SJ, Archambault MP. et al. Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am 2003; 85: 1927-1935.
160 Cinotti G, Patti AM, Vulcano A. et al. Experimental posterolateral spinal fusion with porous ceramics and mesenchymal stem cells. J Bone Joint Surg Br 2004; 86: 135-142.
161 Vanhelleputte PA, Nijs K, Delforge M. et al. Pain during bone marrow aspiration: Prevalence and prevention. J Pain Symptom Manag 2003; 26: 860-866.
162 van Griensven M. Alternative sources for osteochondral tisssue engineering in vivo. Bone-tec 2008: 7-9. November 2008. Hannover; Germany:
163 Jang BJ, Byeon YE, Lim JH. et al. Implantation of canine umbilical cord blood-derived mesenchymal stem cells mixed with beta-tricalcium phosphate enhances osteogenesis in bone defect model dogs. J Vet Sci 2008; 9: 387-393.
164 Kimelman N, Pelled G, Helm GA. et al. Review:Gene- and stem cell-based therapeutics for bone regeneration and repair. Tissue Eng 2007; 13: 1135-1150.
165 Calvert JW, Weiss LE, Sundine MJ. New frontiers in bone tissue engineering. Clin Plast Surg 2003; 30: 641-648.
166 Hutmacher DW, Schantz T, Zein I. et al. Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. J Biomed Mater Res 2001; 55: 203-216.
167 Thomson RC, Wake MC, Yaszemski MJ. et al. Biodegradable polymer scaffolds to regenerate organs. Biopolymers 1995; 122: 245-274.
168 Hou QP, De Bank PA, Shakesheff KM. Injectable scaffolds for tissue regeneration. J Mater Chem 2004; 14: 1915-1923.
169 Hench LL, Polak JM. Third-generation biomedical materials. Science 2002; 295: 1014-1017.
170 Stylios G, Wan TY, Giannoudis P. Present status and future potential of enhancing bone healing using nanotechnology. Injury 2007; 38: S63-S74.
171 Hoffmann A, Ritz U, Alini M. et al. Human osteob-lasts induce proliferation and neo-vessel formation of human umbilical vein endothelial cells in a 3D-coculture. Bone-tec 2008: 7-9. November 2008. Hannover; Germany: