The goal of this project is to use a combination of mesenchymal cells and nanotechnology methods to modulate tendon healing in a rodent model. Growth factors play a major role in tendon and ligament maintenance and repair. Understanding the role of growth factors is necessary to enhance existing surgical techniques with biologically-based therapeutic applications. Mice with a growth factor deficiency demonstrated impaired tendon healing manifested by altered structural and mechanical properties. Tendon repair at the molecular, structural and biomechanical level will be analyzed. Studies both in vitro and in vivo will elucidate the impact of growth factors on tendon regeneration. To achieve the main objective, growth factor cDNA will be delivered to the site of a tendon defect using a novel resorbable polymeric nanofiber based tubular scaffold in a rodent model, and tendon regeneration will be analyzed at the molecular, structural and biomechanical level. The three main aims will be addressed as follows.
In Aim 1 we will investigate the effect of growth factor cDNA therapy on mesenchymal stem cells in vitro. The biochemical and molecular response of mesenchymal stem cells will be analyzed.
In Aim 2, a novel resorbable polymeric tubular nanofiber scaffold will be developed and characterized for local delivery of transduced mesenchymal stem cells to enhance and accelerate tendon regeneration.
In Aim 3, transduced mesenchymal stem cells will be delivered to tendon defects with the nanofiber scaffolds, temporal expression will be determined in vivo, and tendon repair will be examined histologically, at the molecular level for matrix proteins, expression of their genes and by testing the repaired tendon biomechanically.
| Keller, Thomas C; Hogan, MaCalus V; Kesturu, Girish et al. (2011) Growth/differentiation factor-5 modulates the synthesis and expression of extracellular matrix and cell-adhesion-related molecules of rat Achilles tendon fibroblasts. Connect Tissue Res 52:353-64 |
| Hogan, Macalus; Girish, Kesturu; James, Roshan et al. (2011) Growth differentiation factor-5 regulation of extracellular matrix gene expression in murine tendon fibroblasts. J Tissue Eng Regen Med 5:191-200 |
| James, R; Kumbar, S G; Laurencin, C T et al. (2011) Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems. Biomed Mater 6:025011 |
| James, Roshan; Kesturu, Girish; Balian, Gary et al. (2008) Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. J Hand Surg Am 33:102-12 |
