Combined Angiogenic and Osteogenic Factor Delivery Enhances Bone Marrow Stromal Cell-Driven Bone Regeneration

Abstract

Concerted delivery of BMP-4, VEGF, and hBMSCs promoted greater bone formation relative to any single factor or combination of two factors. Materials systems that allows multifactorial presentation more closely mimic natural developmental processes, and these results may have important implications for bone regeneration therapeutics.

Regenerative medicine in orthopaedic surgery

“…18 Immobilization of biologically active macromolecules within polymeric carriers that can meter their release in a predefined profile to control their local concentration and duration of signaling can dramatically improve their effectiveness. A variety of systems have been developed to encapsulate both recombinant growth factors and plasmid DNA encoding these factors in biodegradable polymer platforms useful for tissue engineering, 59,60 and these systems can be designed to enable combinations or sequences of factors to be delivered with well controlled kinetics, 61,62 which more closely mimics the normal developmental and regenerative processes than delivery of single factors. The utility of this approach has recently been demonstrated in the context of bone and muscle regeneration, 54,61,63 and in the formation of new blood vessel networks that can alleviate tissue ischemia and enhance the regenerative potential of cell transplantation strategies.…”

Emerging Ideas: Treatment of Precollapse Osteonecrosis Using Stem Cells and Growth Factors

“…Combined use of VEGF and BMP-2 [19,24,34,35,37,40] and BMP-4 [20,25,36] showed synergistic effects in osteogenesis. It has been shown that combined use of VEGF with one of the most potent BMPs, BMP-6 [23,26], enhances osteogenesis and angiogenesis of mouse bone marrow stem cells in vitro and in vivo [8], however, the effectiveness of this therapy for ON has not been determined.…”

“…Stem cell-mediated bone regeneration augmented with combined use of VEGF and BMPs has been reported but only for BMP-2 [19,24,34,35,37,40] and BMP-4 [20,25,36]. It has been shown that VEGF enhances BMP-6-induced osteogenesis of mouse stem cells in vitro and in vivo, however, the effectiveness of this therapy for ON has not been determined [8].…”

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

“…122 The presentation mode of GFs is a critical step for the generation of a specific tissue response, and several studies have focused on the evaluation of the effect of immobilization technique on cellular response. [123][124][125][126][127][128][129][130][131] For example, it is reported that soluble VEGF induces endothelial cell proliferation, while matrix-bound VEGF promotes vascular sprouting and branching 132 despite other studies revealing opposite responses.…”