Abstract
This study trialled the controlled delivery of growth factors within a biodegradable scaffold in a large segmental bone defect model. We hypothesised that co-delivery of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) followed by bone morphogenetic protein-2 (BMP-2) could be more effective in stimulating bone repair than the delivery of BMP-2 alone. Poly(lactic-co-glycolic acid) (PLGA ) based microparticles were used as a delivery system to achieve a controlled release of growth factors within a medical-grade Polycaprolactone (PCL) scaffold. The scaffolds were assessed in a well-established preclinical ovine tibial segmental defect measuring 3 cm. After six months, mechanical properties and bone tissue regeneration were assessed. Mineralised bone bridging of the defect was enhanced in growth factor treated groups. The inclusion of VEGF and PDGF (with BMP-2) had no significant effect on the amount of bone regeneration at the six-month time point in comparison to BMP-2 alone. However, regions treated with VEGF and PDGF showed increased vascularity. This study demonstrates an effective method for the controlled delivery of therapeutic growth factors in vivo, using microparticles.
Highlights
Most bone fractures do not require intervention and heal spontaneously, stimulated by a choreographed combination of biological signals [1]
Recent research supports the synergistic relationship between vascular endothelial growth factor (VEGF) and Platelet derived growth factor (PDGF) in the generation of stable vasculature [32]. In this investigation in a well-characterised and validated large preclinical animal model, we studied an implant consisting of two elements: a biodegradable structurally supportive, yet highly porous scaffold made from polycaprolactone (PCL) which was combined with Poly(lactic-co-glycolic acid) (PLGA)-based microparticles delivering therapeutic Growth factors (GFs) immobilised in place with platelet rich plasma
Microparticles containing bone morphogenetic protein-2 (BMP-2) exhibited an initial burst release followed a sustained delivery of BMP-2 for 35 consecutive days (Figure 1B)
Summary
Most bone fractures do not require intervention and heal spontaneously, stimulated by a choreographed combination of biological signals [1]. Large bone defects often require intervention and are difficult and costly to treat, causing pain and disability. Worst case scenarios may lead to non-union fractures, a chronic and debilitating issue. The clinical gold standard for the treatment of severe bone defects is autologous bone grafting, but limitations to this approach include donor site morbidity, pain, and lack of graft material [2]. The most common site for severe bone loss in humans, resulting in segmental bone defects, is the tibial diaphysis [3]. Autologous bone grafts contain a mixture of cells, mineralised matrix, and signalling molecules
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