A novel murine segmental femoral graft model

Abstract

To further understand the cellular and molecular mechanisms underlying cortical bone graft healing, we have developed a novel mouse femur model that permits quantitative and molecular analysis of structural bone graft healing. A 4 mm mid-diaphyseal femoral segment was removed and replaced by either immediate implantation of a fresh autograft, a frozen, genetically identical isograft or a frozen allograft from a different strain of mouse, which was secured with a 22-gauge metal intramedullary pin. Healing was evaluated by radiology, histomorphometry, and in situ hybridization. Autograft repair occurred by endochondral bone formation at the host-graft junction and by intramembranous bone formation along the length of the graft bed at 2 weeks, with maturation and remodeling apparent by 4 weeks. Bone repair in allografts and isografts completely relied on endochondral bone formation at the host-graft cortical junction, with absence of periosteal bone formation along the length of the graft, suggesting that live periosteal cells from the donor tissue are necessary for this response. This small animal model of structural bone grafting can be used to evaluate tissue-engineered allografts and novel bone graft substitutes using quantitative and molecularly defined outcome measures.

Impact of MHC mismatch and freezing on bone graft incorporation: An experimental study in rats

“…27 At 8 weeks, the dead bone was still not replaced by creeping substitution of new living bone in any of the groups with bone of low osteocyte density. Our results agree with those presented by Tiyapatanaputi et al 28 In a murine segmental femoral graft model, they found that fresh autograft repair occurred by enchondral bone formation at the host-graft junction and by intramembranous bone formation along the length of the graft. Repair of deep frozen grafts (iso-or allograft), however, relied on enchondral bone formation from the host bed, suggesting that live periosteal cells from the host are necessary for repair.…”

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

“…The absence of periosteum also resulted in 75% reduction of osteoclast numbers on bone graft, which correlated with the poor remodeling activity of the devitalized bone allograft or isograft. In contrast, removing cells from the bone marrow had minimal effects on the periosteal bone formation on the donor bone graft [91].…”

“…To gain an understanding of the cellular and molecular mechanisms that define the superior healing of live bone autograft over allograft, we recently developed a murine segmental bone graft model that permits quantitative analyses of structural bone graft healing, remodeling, and graft-host interactions [91]. This model involves the transplantation of a 4-mm mid-diaphyseal femoral bone segment to a host with the same size defect in the femur.…”

Regenerative medicine in orthopaedic surgery

“…[40][41][42] Radiological and biomechanical outcome measures in a murine femur model have also been developed and have demonstrated the efficacy of these tissue engineered allografts. 43 …”

“…43 Rosa26 transgenic mice were also incorporated into this model so that live isografts that express bgalactosidase could be transplanted into nontransgenic littermates, and the donor cells could be tracked via X-gal stained histology. 44 These studies clearly demonstrated that superior healing observed in the autografts is attributed to the live periosteal cells that actively participate in the early angiogenic, osteogenic, and osteoclastogenic response.…”