Custom-made composite scaffolds for segmental defect repair in long bones

Abstract

Current approaches for segmental bone defect reconstruction are restricted to autografts and allografts which possess osteoconductive, osteoinductive and osteogenic properties, but face significant disadvantages. The objective of this study was to compare the regenerative potential of scaffolds with different material composition but similar mechanical properties to autologous bone graft from the iliac crest in an ovine segmental defect model. After 12 weeks, in vivo specimens were analysed by X-ray imaging, torsion testing, micro-computed tomography and histology to assess amount, strength and structure of the newly formed bone. The highest amounts of bone neoformation with highest torsional moment values were observed in the autograft group and the lowest in the medical grade polycaprolactone and tricalcium phosphate composite group. The study results suggest that scaffolds based on aliphatic polyesters and ceramics, which are considered biologically inactive materials, induce only limited new bone formation but could be an equivalent alternative to autologous bone when combined with a biologically active stimulus such as bone morphogenetic proteins.

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…The bone mineral density and bone strength in sheep is increased relative to human. Moreover, sheep models of critical size defects are extensively applied to evaluate cell-based therapeutic approaches using autologues, allogeneic or xenogeneic MPCs in combination with growth factors and different types of scaffolds to enhance bone regeneration showing significant advantages compared with cell-unloaded (empty) scaffolds [43,53,166,[169][170][171][172][173][174][175][176].…”

Directed migration of human bone marrow mesenchymal stem cells in a physiological direct current electric field

“…osteoblasts and osteoclasts) but also by migration of bone marrow-derived mesenchymal stem cells (BM-MSCs) to sites of injury and subsequent differentiation into mature osteoblasts, thus contributing to bone regeneration (e.g. osteogenesis) (Bianco and Robey, 2001;Granero-Molto et al, 2009;Mauney et al, 2010;Reichert et al, 2010;Reichert et al, 2011). Directional migration of BM-MSCs therefore is an essential process in bone repair.…”

Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

“…We have successfully established this 3 cm critical-sized defect model in sheep tibiae to study the mPCL-TCP scaffold in combination with cells or growth factors including bone morphogenic proteins (BMPs) (211)(212). This model has not only generated a series of highly cited publications (211)(212)(213)(214)(215), but also has attracted large interest in the orthopaedic industry to be used as a preclinical test bed for their bone graft products under development. The model enables control of experimental conditions to allow for direct comparison of products against a library of benchmarks and gold standards we have developed over the last 5 years (we have performed more than 200 operations using this model todate).…”

“…Our research group at the Queensland University of Technology (QUT; Brisbane, Australia) has spent the last 5 years developing a world-leading defect model to study pre-clinically different treatment options for cases of large volume segmental bone loss (159,210). We have successfully established this 3 cm critical-sized defect model in sheep tibiae to study the mPCL-TCP scaffold in combination with cells or growth factors including bone morphogenic proteins (BMPs) (211)(212). This model has not only generated a series of highly cited publications (211)(212)(213)(214)(215), but also has attracted large interest in the orthopaedic industry to be used as a preclinical test bed for their bone graft products under development.…”