Local controlled release of VEGF and PDGF from a combined brushite–chitosan system enhances bone regeneration

The development of non-viral gene-activated matrices for bone regeneration using polyethyleneimine (PEI) and collagen-based scaffolds

“…In order to heal large defects, biomaterial scaffolds for tissue engineering applications have primarily been modified to contain growth factors in the form of recombinant proteins for greater therapeutic potential [1][2][3][4][5]. Recently, due to the limitations associated with protein delivery [6,49], gene therapy has alternatively been applied to provide sustained protein production by transfected cells over an extended time frame to ultimately render an enhanced therapeutic response.…”

“…Scaffolds developed from biomaterials act as templates for tissue formation where the interaction between the scaffold, infiltrating cells and the aforementioned cues is intrinsic to its success. Biomaterial scaffolds for tissue engineering applications have primarily been modified to contain growth factors in the form of recombinant proteins to boost the therapeutic response [1][2][3][4][5]. However, using proteins in this environment is associated with a number of distinct disadvantages such as the large dose required, the need for repeated applications, poor distribution, expense, short half-life and protein instability [6].…”

Development of a gene-activated scaffold platform for tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds

“…While the use of biomaterial scaffolds for the treatment of bone and cartilage defects has shown some promise, the addition of bioactive molecules such as growth factors can significantly enhance healing, particularly in large defects [1,2]. For example, absorbable collagen sponges are used clinically to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in spinal fusion procedures (Medtronic's INFUSE ®) [3].…”

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

“…167 Combined results of Kempen et al 165 and Patel et al 45 suggest that the enhanced effect of VEGF and BMP-2 combination is both time-and location-dependent, which is not surprising due to the complexity of the pathways involved in bone healing. While Kempen et al 165 displayed an extremely high VEGF burst release of around 80%, De la Riva et al 166 reduced this stage to 20% and obtained considerable enhanced bone formation in the dual-release system they proposed (combination of VEGF and PDGF). Shah et al 167 showed that dual release of VEGF and BMP-2 from polyelectrolyte multilayers induced a more complete bone architecture than the single dose of BMP-2, promoting a greater initial concurrent vascularization process and consequent introduction of more cells in the interior on the scaffolds.…”

“…Most of the reports that assessed the in vivo release profiles used radioactivity as a tracing agent to identify the implanted molecules of interest. 160,166,168 Indirect GF delivery…”