BME Colloquium Series: David L. Butler, Ph.D.

Functional Tissue Engineering for Tendon Repair: Scaffolds, Stem Cells, Stimulation and Developmental Cues

Abstract

Achilles and rotator cuff tendon injuries as well as tendon graft reconstructions are persistent and complex musculoskeletal problems. Using a multi-faceted functional tissue engineering approach, our group has been improving repair in a rabbit patellar tendon model using tissue engineered constructs (TECs) formed by suspending autologous mesenchymal stem cells (MSCs) in collagen-based gel and sponge scaffolds. Inserting these TECs into central PT defects significantly improves repair stiffness, particularly in the functional in vivo loading range. Mechanically stimulating these constructs in culture further improves both TEC and repair stiffness. The strong correlation between these measures suggests that certain in vitro mechanical parameters may predict in vivo outcome and that optimizing stiffness in culture will ultimately enhance soft tissue repair.

Recently, we have also been using developmental biology to improve patellar tendon repair across multiple species. By monitoring changes in local murine gene expression during development, we hope to identify developmental cues and signaling pathways controlling tenogenesis. This information could lead to growth factors that might be introduced into cell-based TECs to improve rabbit and then ovine PT repair. As part of this effort, we have developed double transgenic reporter mouse strains in which cells transcribing the Col1 gene express cytoplasmic GFP and cells transcribing the Col2 gene express cytoplasmic ECFP-cyan. We have used these murine models to also develop a Col2 transgenic rabbit. We now seek to create spatial and temporal maps of gene expression within the developing tendon to benchmark healing and repair of adult PT injuries across species. Ultimately, our goal is to determine whether normal tendon development could provide clues into tenogenesis, especially using mesenchymal stem cell therapy.