Microparticles for Sustained Growth Factor Delivery in the Regeneration of Critically-Sized Segmental Tibial Bone Defects

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.

Microparticles for controlled growth differentiation factor 6 delivery to direct adipose stem cell‐based nucleus pulposus regeneration

“…Previously, we have developed improved methods for growth factor delivery by decoupling release kinetics from polymer degradation by the inclusion of a more hydrophilic component, such as polyethylene glycol (PEG; White et al, ). The addition of an “in‐house” developed triblock copolymer, PLGA–PEG–PLGA provides additional control over polymer hydration to achieve sustained delivery (G. Kirby et al, ; White et al, )…”

“…Previously, we have developed improved methods for growth factor delivery by decoupling release kinetics from polymer degradation by the inclusion of a more hydrophilic component, such as polyethylene glycol (PEG; White et al, 2013). The addition of an "inhouse" developed triblock copolymer, PLGA-PEG-PLGA provides additional control over polymer hydration to achieve sustained delivery (G. Kirby et al, 2016;White et al, 2013) Therefore, the aim of this study was to encapsulate rhGDF6 in novel PLGA/PLGA-PEG-PLGA MPs to control its release over a defined timescale in vitro. Polymer MP delivery was investigated as this system offers high growth factor entrapment efficiency, the dry MPs have a long storage life, and MPs can be easily incorporated into injectable load-bearing hydrogel systems without significant detriment to mechanical properties [37].…”

Adoption of nanodiamonds as biomedical materials for bone repair

“…Preliminary studies are reporting the use of NDs as multiple protein delivering vehicle [16]. Researchers have shown that the combined delivery of VEGF, PDGF and BMP-2 would lead to more efficient bone regeneration than BMP-2 alone based on the rationale that this would more closely mimic the biological events leading to bone formation [35]. The angiogenic factors would direct the processes for early vasculature, promoting BMP-2 induced osteogenic differentiation and bone formation.…”

Proteína Morfogenética Ósea y su Opción como Tratamiento de la Fisura Alveolar

“…También se ha estudiado la liberación controlada de diferentes factores de crecimiento en una matriz reabsorbible de policaprolactona en defectos óseo de 3 cm en tibia de ovino (Kirby et al, 2016). En su diseño experimental, comparó un grupo de MP de rhBMP-2 con MP de un conjunto de factores de crecimiento; factor de crecimiento vascular endotelial (VRGF), factor de crecimiento derivado de plaquetas (PFGF) y rhBMP-2.…”