Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury

To examine how the chemotactic agent stromal cell-derived factor-1alpha (SDF-1 alpha) modulates the unique cellular milieu within rotator cuff muscle following tendon injury, we developed an injectable, heparin-based microparticle platform to locally present SDF-1 alpha within the supraspinatus muscle following severe rotator cuff injury. SDF-1 alpha-loaded, degradable, N-desulfated heparin-based microparticles were fabricated, injected into a rat model of severe rotator cuff injury, and retained for up to 7 days at the site. The resultant inflammatory cell and mesenchymal stem cell populations were analyzed compared to uninjured contralateral controls, and after 7 days, the fold change in anti-inflammatory, M2-like macrophages (CD11b+CD68+CD163+, 4.3x fold change) and mesenchymal stem cells (CD29+CD44+CD90+, 3.0x) was significantly greater in muscles treated with SDF-1 alpha-loaded microparticles than unloaded microparticles or injury alone. Our results indicate that SDF-1 alpha-loaded microparticles may be a novel approach to shift the cellular composition within the supraspinatus muscle and create a more pro-regenerative milieu, which may provide a platform to improve muscle repair following rotator cuff injury in the future.