A biomimetic growth factor delivery strategy for enhanced regeneration of iliac crest defects

PubMedID: 23782488The importance of provision of growth factors in the engineering of tissues has long been shown to control the behavior of the cells within the construct and several approaches were applied toward this end. In nature, more than one type of growth factor is known to be effective during the healing of tissue defects and their peak concentrations are not always simultaneous. One of the most recent strategies includes the delivery of a combination of growth factors with the dose and timing to mimic the natural regeneration cascade. The sequential delivery of bone morphogenetic proteins BMP-2 and BMP-7 which are early and late appearing factors during bone regeneration, respectively, was shown in vitro to enhance osteoblastic differentiation of bone marrow derived mesenchymal stem cells. In the present study, the aim was to study the effectiveness of this delivery strategy in a rabbit iliac crest model. 3D plotted poly(?-caprolactone) scaffolds were loaded with BMP carrying nanoparticles to achieve: (a) single BMP-2 or BMP-7 delivery, and (b) their combined delivery in a simultaneous or (c) sequential (biomimetic) fashion. After eight weeks of implantation, computed tomography and biomechanical tests showed better mineralized matrix formation and bone-implant union strength at the defect site in the case of sequential delivery compared to single or simultaneous delivery modes. Bone mineral density (BMD) and push-out stress were: 33.65±2.25 g cm-3 and 14.5±2.28 MPa, respectively, and almost 2.5 fold higher in comparison to those without growth factors (BMD: 14.14±1.21 g cm-3; PS: 6.59±0.65 MPa). This study, therefore, supports those obtained in vitro and emphasizes the importance of mimicking the natural timing of bioavailability of osteogenic factors in improving the regeneration of critical-sized bone defects. © 2013 IOP Publishing Ltd

Proliferation and differentiation of mesenchymal stem cells in chitosan scaffolds loaded with nanocapsules containing bone morphogenetic proteins-4, Platelet-derived growth factor and insulin-like growth factor 1

Periodontal regeneration is a complex healing pattern of soft and hard periodontal tissues. Recent approaches in reconstructive biology utilize mechanical, cellular or biologic mediators to facilitate reconstruction/regeneration of a particular tissue. In this study, the concept of tissue engineering was applied by using biodegradable chitosan scaffolds containing nanocapsules having different degradation rates and loaded with various growth factors (GFs). For this purpose, nanocapsules of faster degrading poly(lacticacid-co-glycolic acid) (PLGA) and slower degrading poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) were separately loaded with bone morphogenetic protein 4 (BMP-4), platelet-derived growth factor (PDGF) and Insulin-like growth factor 1 (IGF-I) and nanocapsules were incorporated into chitosan scaffolds. PLGA capsules had a particle size in the range of 190–615 nm with an average diameter of 327 nm where PHBV capsules were found to have particle size in the range of 255–712 nm with a larger mean diameter of 438 nm. The morphology of chitosan scaffolds showed a sponge-like open porous microstructure with pore size around 100-200 µm. Human mesenchymal stem cells were used in in vitro studies. It was observed that simultaneous fast delivery of BMP-4 and PDGF led to highest proliferation rate. All cell seeded scaffolds were positive for mineralization which was determined by von Kossa staining. © 2014 American Scientific Publishers. All rights reserved