Context-Dependent Effects of Platelet-Derived Growth Factor on Osteogenesis in 2D and 3D Fibrin Models.

BACKGROUND

Nonunion is a common complication after arthrodesis that often necessitates additional surgery. Augmentation with autograft is the standard of care, but nonunion rates remain high. Recombinant platelet-derived growth factor (rhPDGF-bb) is another adjuvant commonly used for ankle fusion and has shown similar effectiveness to autograft. To our knowledge, no study has investigated the effect of PDGF-bb on a representative cell population of an arthrodesis and in the fibrin-rich fusion environment. This study tested the hypothesis that PDGF-bb, as a standalone treatment, induces osteogenesis of this representative population of cells in 2D and 3D.

METHODS

Mesenchymal stem cells (MSCs) or marrow-derived cells (MDCs) were cultured in 2D monolayer or 3D fibrin cultures, and were evaluated for temporal osteogenesis via mineralization assays, gene expression, micro-CT, and histology.

RESULTS

PDGF-bb enhanced mineralization of both MSCs and MDCs in monolayer culture; however, PDGF-bb downregulated osteogenic gene expression in 2D. Within 3D hMSCs, PDGF-bb increased bone volume but significantly reduced radiopacity, and within 3D hMDCs there was no significant difference from the control.

CONCLUSION

This study demonstrates the context- and cell population-dependent ability of PDGF-bb to induce osteogenic mineralization in 2 distinct in vitro models. The findings suggest that PDGF-bb's mitogenic activity promotes proliferation and matrix deposition in 2D environments, but its effects may be limited in 3D fibrin constructs where we postulate that spatial constraints restrict proliferation. The evaluation of PDGF-bb, and other newly developed adjuvants, in both 2D and 3D in vitro assays is required to determine context-dependent osteogenesis. This understanding provides a basis for future experiments to assist in determining the ideal patients for utilization of PDGF-bb and determine if there are instances when other adjuvants may be considered.