Extracellular matrix scaffolds are repopulated by bone marrow-derived cells in a mouse model of Achilles tendon reconstruction

The extracellular matrix derived from porcine small intestinal submucosa (SIS-ECM), an FDA-approved material currently used clinically for rotator cuff repair, has been shown to attract bone marrow-derived cells during in vivo remodeling of a subcutaneous implant and produce chemoattractant peptides following chemical degradation in vitro. The purpose of the present study was to determine if bone marrow-derived cells participate in the long-term remodeling of the Achilles tendon in a mouse model when repaired with SIS-ECM. A 2-mm gap was produced in the Achilles tendon of 40 chimeric mice produced to express green fluorescent protein (GFP) in all of their bone marrow-derived cells. Tendons were repaired by replacing the resected section with autologous tendon tissue or with a single layer sheet of lyophilized SIS-ECM. Four animals from each treatment group were sacrificed at 1, 2, 4, 8, and 16 weeks, and sections were harvested for histologic and fluorescence microscopy. Both groups showed accumulation of GFP-expressing marrow-derived cells at the site of tendon remodeling at 1 and 2 weeks that were associated with areas of angiogenesis and inflammation. By 16 weeks, the SIS-ECM-treated group showed GFP expressing cells throughout the remodeled tendon in the absence of any inflammatory response, while the autologous tendon repair group showed no GFP expressing cells within the tendon except for occasional cells in the lumen of blood vessels. An SIS-ECM scaffold used for tendon repair recruits a population of bone marrow-derived cells that participates in the long-term remodeling process. The ability of SIS-ECM to recruit a population of marrow-derived cells to the remodeling site may alter the default mechanism of tendon healing. The involvement of these cells in the remodeling process may explain in part the process of site specific constructive remodeling as opposed to scar tissue formation when the ECM is used as a biologic scaffold for tendon reconstruction.