Mechanical and radiological assessment of the influence of rhTGFβ‐3 on bone regeneration in a segmental defect in the ovine tibia: Pilot study

Abstract

Limitations in the use of autologous bone graft, which is the gold standard therapy in bone defect healing, drive the search for alternative treatments. In this study the influence of rhTGFb-3 on mechanical and radiological parameters of a healing bone defect in the sheep tibia was assessed. In the sheep, an 18-mm long osteoperiosteal defect in the tibia was treated by rhTGFb-3 seeded on a poly(L/DL-lactide) carrier (n ¼ 4). In a second group (n ¼ 4), the defect was treated by the carrier only, in a third group (n ¼ 4) by autologous cancellous bone graft, and in a fourth group (n ¼ 2) the defect remained blank. The healing process of the defect was assessed by weekly in vivo stiffness measurements and radiology as well as by quantitative computed tomographic assessment of bone mineral density (BMD) every 4 weeks. The duration of the experiment was 12 weeks under loading conditions. In the bone graft group, a marginally significant higher increase in stiffness was observed than in the PLA/rhTGFb-3 group ( p ¼ 0.06) and a significantly higher increase than in the PLA-only group ( p ¼ 0.03). The radiographic as well as the computed tomographic evaluation yielded significant differences between the groups ( p ¼ 0.03), indicating the bone graft treatment (bone/per area, 83%; BMD, 0.57 g/cm 3 ) performing better than the PLA/rhTGFb-3 (38%; 0.23 g/cm 3 ) and the PLA-only treatment (2.5%; 0.09 g/cm 3 ), respectively. Regarding the mechanical and radiological parameters assessed in this study, we conclude that rhTGFb-3 has a promoting effect on bone regeneration. However, under the conditions of this study, this effect does not reach the potential of autologous cancellous bone graft transplantation. ß

The efficacy of allogeneic mesenchymal precursor cells for the repair of an ovine tibial segmental defect

“…The segmental defect model, utilising a locking intramedullary nail, performed well with no withdrawals from the study. Numerous studies have documented the use of either canine or ovine tibial or femoral segmental defects to evaluate the functionality of bio-ceramics with or without the addition of osteogenic or osteoinductive factors, or a combination of both (27)(28)(29)(30)(31)(32). The ovine tibial model provides a rigorous environment in which to evaluate new therapies.…”

Preclinical Animal Models for Segmental Bone Defect Research and Tissue Engineering

“…Another study using an ovine segmental defect model investigated the in fl uence of rhTGF b -3 on mechanical and radiological parameters of a healing bone defect (Maissen et al 2006 ) . In 4-5-year-old sheep, an 18 mm long osteoperiosteal defect in the tibia fi xed with a unilateral external fi xator was treated by rhTGF b -3 delivered by a poly(L/DL-lactide) carrier, with the carrier only, with autologous cancellous bone graft, or remained untreated.…”

Strategies and First Advances in the Development of Prevascularized Bone Implants

“…Despite differences in the bone microstructure, the value of sheep and goats is the modeling of human bone turnover and remodeling [104]. They have been used for segmental defect models [105], vertebral bone defect models including studies testing bone substitute materials [106], the effect of growth factors [107], and tissue engineering strategies [73]. …”