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Although this has been successful in animal models of therapeutic angiogenesis this success has not, to date, been able to be translated to the clinic. Recent studies have shown that the combination of angiogenic and osteogenic factors can stimulate bone healing and regeneration. Therefore, the Balsalazide ability to deliver a combined delivery system of growth factors at different rate kinetics locally from biodegradable scaffolds could enhance the reparative mechanism of critical sized bone defects; thus, Nobiletin mimicking the in vivo bone repair conditions.This comb inationof PDGF BB and VEGF init ia ted formation and maturation of a significant number of blood vessels.A multiple release of growth factors such as VEGF and BMP may in fact be able to mimic the conditions in bone fracture repair.Hence, a scaffold able to release an active angiogenic factor will promote early vascularisation and attract osteogenic precursor cells.Figure demonstrates the significant effect of the release of angiogenic factors from a biodegradable scaffold seeded with human bone marrow stromal cells on the regeneration of bone in a critical sized mouse femur defect.Hence, the comb inedeffectofhuman bone marrowst romalorenriched mesenchymal stem cells seeded onto these new generation of growth factor encapsulated scaffolds could result in the codevelopment of vessels and bone in situ, providing a reciprocal approach to the fast development of vascularised engineered bone constructs.PLGA scaffolds containing a combination of plasmids encoding DNA for BMP, VEGF and human bone marrow stromal cells promoted greater bone formation when implanted into the subcutaneous tissue of SCID mice relative to a single factor or a combination of two factors. These generated scaffolds have the abilitytorele ase activeBM P andpr omoteosteoprogenitor differentiation and bone formation in vitro and in vivo. Development of complex biomimetic scaffolds has resulted in the ability kinetically to release VEGF quickly followed by slow release of BMP mimicking the sequences these growth factors are released in fracture repair process.The addition of seeded human bone marrow cells or progenitor cells onto these dual release scaffolds will produce some of the key components to enhance the repair of delayed or nonunion delayed fractures.With the progression of new research tools osteogenic and angiogenic molecules involved in the signalling pathway cascade in the development of bone are slowly being elucidated.Understanding the paracrine relationship between bone cells and endothelial cells and the signalling molecules therein will undoubtedly unveil key mechanisms involved in bone morphogenesis, and offer insights into the development and of new strategies for the delivery of targeted therapies to bone related diseases particularly individuals at risk for delayed repair or nonunions.Increasing our understanding will ultimately help in devising new approaches in vascularised engineered tissue constructs.Optimising drug delivery to angiogenic and antiangiogenic molecules that effect vessel growth in the bone environment may prove beneficial for targeting either bone destruction or inducing bone growth.Slow release growth factorscaffold formulations, gene therapy and stem cells are all currently being used to enhance bone fracture repair and regeneration.Groups have now developed intelligent scaffolds that can now release growth factors with appropriate release kinetics to induce angiogenesis and bone morphogenes is.

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