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.

Radiographic and Histological Analysis of a Synthetic Bone Graft Substitute Eluting Gentamicin in the Treatment of Chronic Osteomyelitis

“…However, our study findings are similar to a large animal model in sheep that analysed the resorption pattern of CERAMENT ® |G and formation of new bone using radiographs, MRI, µCT, Dexa-scan and histology. The bone repair was noted to commence in the periphery and move towards the centre of the void 44.…”

A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair

“…While donor site morbidity remains an uncommon complication, the harvesting of bone autografts is a procedure that is unsuitable for some patients, especially in the very young or critically injured patients. Consequently, bone allografts persist as a commonly used alternative for promoting bone healing, despite the increasing availability of artificial BG substitutes …”

“…Consequently, bone allografts persist as a commonly used alternative for promoting bone healing, despite the increasing availability of artificial BG substitutes. 5 Bone allografts are sterilized by freeze drying and/or irradiation and these processes ensure that live cells are no longer present in the donor graft, but they also destroy many of the osteogenic proteins that contribute to bone healing. This greatly reduces the osteogenic potential of allografts compared with autografts, such that it chiefly facilitates osteoconduction and a "creeping substitution" of new bone.…”

Decellularized adipose matrix provides an inductive microenvironment for stem cells in tissue regeneration

“…Bone has significant capacity of regeneration, but patients with large-scale bone defects need surgical autogenous bone transplantation, which causes damage and infection of the donor site[ 120 - 122 ]. Artificial composite scaffolds are poorly biocompatible and cannot support vascular regeneration and bone tissue growth[ 122 ], while the source of acellular bone tissue is insufficient to meet clinical needs[ 123 , 124 ]. Mohiuddin et al[ 125 ] used DAM hydrogels to treat C57BL/6 mice for critical size repair of femoral defects.…”