Delivery of Platelet-Derived Growth Factor as a Chemotactic Factor for Mesenchymal Stem Cells by Bone-Mimetic Electrospun Scaffolds

Abstract

The recruitment of mesenchymal stem cells (MSCs) is a vital step in the bone healing process, and hence the functionalization of osteogenic biomaterials with chemotactic factors constitutes an important effort in the tissue engineering field. Previously we determined that bone-mimetic electrospun scaffolds composed of polycaprolactone, collagen I and nanohydroxyapatite (PCL/col/HA) supported greater MSC adhesion, proliferation and activation of integrin-related signaling cascades than scaffolds composed of PCL or collagen I alone. In the current study we investigated the capacity of bone-mimetic scaffolds to serve as carriers for delivery of an MSC chemotactic factor. In initial studies, we compared MSC chemotaxis toward a variety of molecules including PDGF-AB, PDGF-BB, BMP2, and a mixture of the chemokines SDF-1α, CXCL16, MIP-1α, MIP-1β, and RANTES. Transwell migration assays indicated that, of these factors, PDGF-BB was the most effective in stimulating MSC migration. We next evaluated the capacity of PCL/col/HA scaffolds, compared with PCL scaffolds, to adsorb and release PDGF-BB. We found that significantly more PDGF- BB was adsorbed to, and subsequently released from, PCL/col/HA scaffolds, with sustained release extending over an 8-week interval. The PDGF-BB released was chemotactically active in transwell migration assays, indicating that bioactivity was not diminished by adsorption to the biomaterial. Complementing these studies, we developed a new type of migration assay in which the PDGF-BB-coated bone-mimetic substrates were placed 1.5 cm away from the cell migration front. These experiments confirmed the ability of PDGF-BB-coated PCL/col/HA scaffolds to induce significant MSC chemotaxis under more stringent conditions than standard types of migration assays. Our collective results substantiate the efficacy of PDGF-BB in stimulating MSC recruitment, and further show that the incorporation of native bone molecules, collagen I and nanoHA, into electrospun scaffolds not only enhances MSC adhesion and proliferation, but also increases the amount of PDGF-BB that can be delivered from scaffolds.

Platelet-rich Concentrates Differentially Release Growth Factors and Induce Cell Migration In Vitro

“…As previously described using the single recombinant protein, TGF-ß1 had no effect on MSC migration [36] and negatively correlated with HUVEC migration [34]. However, the negative correlation uncovered between PDGF-AB and cell migration appears to be at odds with an earlier study [26], in which recombinant human PDGF-AB induced migration of MSC. The discrepancy in the results could be due to a Data are presented as mean ± SD from triplicate measurements of 11 samples.…”

Nano-biphasic calcium phosphate/polyvinyl alcohol composites with enhanced bioactivity for bone repair via low-temperature three-dimensional printing and loading with platelet-rich fibrin

“…VEGF and PDGF mainly promote angiogenesis through recruiting endothelial cells and forming tubules. 59 PDGF also promotes BMSC recruitment, 60 and IGF plays a part in neoangiogenesis. 61 TGF mainly recruits osteoblast precursors.…”

Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?

“…Another growth factor involved in MSC migration is hepatocyte growth factor (HGF), which binds to c-met [63,68,80] . Both PDGF-BB and HGF have been loaded on gels or scaffolds as a means to improve the in vitro migration of MSCs [92,93] .…”