Bone Marrow Mobilization and Local Stromal Cell-Derived Factor-1α Delivery Enhances Nascent Supraspinatus Muscle Fiber Growth.

Rotator cuff tear is a significant problem that leads to poor clinical outcomes due to muscle degeneration after injury. The objective of this study was to synergistically increase the number of proregenerative cells recruited to injure rotator cuff muscle through a novel dual treatment system, consisting of a bone marrow mobilizing agent (VPC01091), hypothesized to "push" prohealing cells into the blood, and localized delivery of stromal cell-derived factor-1α (SDF-1α), to "pull" the cells to the injury site. Immediately after rotator cuff tendon injury in rat, the mobilizing agent was delivered systemically, and SDF-1α-loaded heparin-based microparticles were injected into the supraspinatus muscle.

Injection of Micronized Human Amnion/Chorion Membrane Results in Increased Early Supraspinatus Muscle Regeneration in a Chronic Model of Rotator Cuff Tear.

Surgical repair of severe rotator cuff tear often results in retear due to unaddressed muscle degeneration. The objective of this study was to test the regenerative potential of micronized dehydrated Human Amnion/Chorion Membrane (dHACM), in a clinically relevant delayed reattachment model of rotator cuff repair. Micronized dHACM was injected into rat supraspinatus muscle during tendon re-attachment surgery, three weeks after original tendon injury.

Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis.

As a potential treatment for osteoarthritis (OA), we have developed injectable and hydrolytically degradable heparin-based biomaterials with tunable sulfation for the intra-articular delivery of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a protein known to inhibit plasmin which may degrade extracellular matrix within OA joints. We first assessed the effect of heparin sulfation on TSG-6 anti-plasmin activity and found that while fully sulfated (Hep) and heparin desulfated at only the N position (Hep-N) significantly enhanced TSG-6 bioactivity in vitro, fully desulfated heparin (Hep-) had no effect, indicating that heparin sulfation plays a significant role in modulating TSG-6 bioactivity. Next, TSG-6 loaded, degradable 10 wt% Hep-N microparticles (MPs) were delivered via intra-articular injection into the knee at 1, 7, and 15 days following medial meniscal transection (MMT) injury in a rat model.