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Establishment and effects of allograft and synthetic bone graft substitute treatment of a critical size metaphyseal bone defect model in the sheep femur

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Hettwer, Werner ; Horstmann, Peter F ; Bischoff, Sabine ; Güllmar, Daniel ; Reichenbach, Jürgen R ; Poh, Patrina S P ; van Griensven, Martijn ; Gras, Florian ; Diefenbeck, Michael. / Establishment and effects of allograft and synthetic bone graft substitute treatment of a critical size metaphyseal bone defect model in the sheep femur. In: APMIS - Journal of Pathology, Microbiology and Immunology. 2019 ; Vol. 127, No. 2. pp. 53-63.

Bibtex

@article{d7e4bc374e184f139129e45cf1d8da4a,
title = "Establishment and effects of allograft and synthetic bone graft substitute treatment of a critical size metaphyseal bone defect model in the sheep femur",
abstract = "Assessment of bone graft material efficacy is difficult in humans, since invasive methods like staged CT scans or biopsies are ethically unjustifiable. Therefore, we developed a novel large animal model for the verification of a potential transformation of synthetic bone graft substitutes into vital bone. The model combines multiple imaging methods with corresponding histology in standardized critical sized cancellous bone defect. Cylindrical bone voids (10 ml) were created in the medial femoral condyles of both hind legs (first surgery at right hind leg, second surgery 3 months later at left hind leg) in three merino-wool sheep and either (i) left empty, filled with (ii) cancellous allograft bone or (iii) a synthetic, gentamicin eluting bone graft substitute. All samples were analysed with radiographs, MRI, μCT, DEXA and histology after sacrifice at 6 months. Unfilled defects only showed ingrowth of fibrous tissue, whereas good integration of the cancellous graft was seen in the allograft group. The bone graft substitute showed centripetal biodegradation and new trabecular bone formation in the periphery of the void as early as 3 months. μCT gave excellent insight into the structural changes within the defects, particularly progressive allograft incorporation and the bone graft substitute biodegradation process. MRI completed the picture by clearly visualizing soft tissue ingrowth into unfilled bone voids and presence of fluid collections. Histology was essential for verification of trabecular bone and osteoid formation. Conventional radiographs and DEXA could not differentiate details of the ongoing transformation process. This model appears well suited for detailed in vivo and ex vivo evaluation of bone graft substitute behaviour within large bone defects.",
keywords = "Allografts, Animals, Bone Substitutes/therapeutic use, Bone Transplantation/methods, Calcium Sulfate, Cancellous Bone/growth & development, Durapatite, Female, Femur/surgery, Magnetic Resonance Imaging, Models, Animal, Sheep",
author = "Werner Hettwer and Horstmann, {Peter F} and Sabine Bischoff and Daniel G{\"u}llmar and Reichenbach, {J{\"u}rgen R} and Poh, {Patrina S P} and {van Griensven}, Martijn and Florian Gras and Michael Diefenbeck",
note = "{\textcopyright} 2019 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Medical Microbiology and Pathology.",
year = "2019",
month = feb,
doi = "10.1111/apm.12918",
language = "English",
volume = "127",
pages = "53--63",
journal = "APMIS - Journal of Pathology, Microbiology and Immunology",
issn = "0903-4641",
publisher = "Wiley Online",
number = "2",

}

RIS

TY - JOUR

T1 - Establishment and effects of allograft and synthetic bone graft substitute treatment of a critical size metaphyseal bone defect model in the sheep femur

AU - Hettwer, Werner

AU - Horstmann, Peter F

AU - Bischoff, Sabine

AU - Güllmar, Daniel

AU - Reichenbach, Jürgen R

AU - Poh, Patrina S P

AU - van Griensven, Martijn

AU - Gras, Florian

AU - Diefenbeck, Michael

N1 - © 2019 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Medical Microbiology and Pathology.

PY - 2019/2

Y1 - 2019/2

N2 - Assessment of bone graft material efficacy is difficult in humans, since invasive methods like staged CT scans or biopsies are ethically unjustifiable. Therefore, we developed a novel large animal model for the verification of a potential transformation of synthetic bone graft substitutes into vital bone. The model combines multiple imaging methods with corresponding histology in standardized critical sized cancellous bone defect. Cylindrical bone voids (10 ml) were created in the medial femoral condyles of both hind legs (first surgery at right hind leg, second surgery 3 months later at left hind leg) in three merino-wool sheep and either (i) left empty, filled with (ii) cancellous allograft bone or (iii) a synthetic, gentamicin eluting bone graft substitute. All samples were analysed with radiographs, MRI, μCT, DEXA and histology after sacrifice at 6 months. Unfilled defects only showed ingrowth of fibrous tissue, whereas good integration of the cancellous graft was seen in the allograft group. The bone graft substitute showed centripetal biodegradation and new trabecular bone formation in the periphery of the void as early as 3 months. μCT gave excellent insight into the structural changes within the defects, particularly progressive allograft incorporation and the bone graft substitute biodegradation process. MRI completed the picture by clearly visualizing soft tissue ingrowth into unfilled bone voids and presence of fluid collections. Histology was essential for verification of trabecular bone and osteoid formation. Conventional radiographs and DEXA could not differentiate details of the ongoing transformation process. This model appears well suited for detailed in vivo and ex vivo evaluation of bone graft substitute behaviour within large bone defects.

AB - Assessment of bone graft material efficacy is difficult in humans, since invasive methods like staged CT scans or biopsies are ethically unjustifiable. Therefore, we developed a novel large animal model for the verification of a potential transformation of synthetic bone graft substitutes into vital bone. The model combines multiple imaging methods with corresponding histology in standardized critical sized cancellous bone defect. Cylindrical bone voids (10 ml) were created in the medial femoral condyles of both hind legs (first surgery at right hind leg, second surgery 3 months later at left hind leg) in three merino-wool sheep and either (i) left empty, filled with (ii) cancellous allograft bone or (iii) a synthetic, gentamicin eluting bone graft substitute. All samples were analysed with radiographs, MRI, μCT, DEXA and histology after sacrifice at 6 months. Unfilled defects only showed ingrowth of fibrous tissue, whereas good integration of the cancellous graft was seen in the allograft group. The bone graft substitute showed centripetal biodegradation and new trabecular bone formation in the periphery of the void as early as 3 months. μCT gave excellent insight into the structural changes within the defects, particularly progressive allograft incorporation and the bone graft substitute biodegradation process. MRI completed the picture by clearly visualizing soft tissue ingrowth into unfilled bone voids and presence of fluid collections. Histology was essential for verification of trabecular bone and osteoid formation. Conventional radiographs and DEXA could not differentiate details of the ongoing transformation process. This model appears well suited for detailed in vivo and ex vivo evaluation of bone graft substitute behaviour within large bone defects.

KW - Allografts

KW - Animals

KW - Bone Substitutes/therapeutic use

KW - Bone Transplantation/methods

KW - Calcium Sulfate

KW - Cancellous Bone/growth & development

KW - Durapatite

KW - Female

KW - Femur/surgery

KW - Magnetic Resonance Imaging

KW - Models, Animal

KW - Sheep

U2 - 10.1111/apm.12918

DO - 10.1111/apm.12918

M3 - Journal article

C2 - 30698307

VL - 127

SP - 53

EP - 63

JO - APMIS - Journal of Pathology, Microbiology and Immunology

JF - APMIS - Journal of Pathology, Microbiology and Immunology

SN - 0903-4641

IS - 2

ER -

ID: 59373707