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

• Type of Material: Article
• Authors: L. E. Tellier, Georgia Institute of Technology; J. R. Krieger, Georgia Institute of Technology; A. L. Brimeyer, Georgia Institute of Technology; A. C. Coogan, Georgia Institute of Technology; A. A. Falis, Georgia Institute of Technology; T. E. Rinker, Georgia Institute of Technology; A. Schudel, Georgia Institute of Technology; S. N. Thomas, Georgia Institute of Technology; C. D. Jarrett, Wilmington Health Orthopedic Medical Center; Nick Willett, Emory University; Edward Botchwey, Emory University; Johnna Sue Temenoff, Emory University
• Language: English
• Date: 2018-06-01
• Publisher: Emory University Libraries
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018, The Regenerative Engineering Society.
• Final Published Version (URL): http://dx.doi.org/10.1007/s40883-018-0052-4
• Title of Journal or Parent Work: Regenerative Engineering and Translational Medicine
• Volume: 4
• Issue: 2
• Start Page: 92
• End Page: 103
• Grant/Funding Information: This research was supported in part by the NIH-funded Research Resource for Integrated Glycotechnology (NIH P41GM103390) to the Complex Carbohydrate Research Center at the University of Georgia.; This research was also supported by a Georgia Tech/Emory University Immunoengineering Center Seed Grant and an Emory Department of Orthopaedics Seed Grant.; This research was funded by NSF Stem Cell Biomanufacturing IGERT (DGE 0965945); by the NIH (1R01AR071026); and by National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH (R01AR063692).
• Keywords: macrophages; microparticles; mesenchymal stem cells; stromal cell-derived factor-1α; heparin
• Research Categories: Engineering, Biomedical; Health Sciences, Medicine and Surgery

Abstract

To examine how the chemotactic agent stromal cell-derived factor-1alpha (SDF-1α) modulates the unique cellular milieu within rotator cuff muscle following tendon injury, we developed an injectable, heparin-based microparticle platform to locally present SDF-1α within the supraspinatus muscle following severe rotator cuff injury. SDF-1α-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+, 4.3× fold change) and mesenchymal stem cells (CD29+CD44+CD90+, 3.0×) was significantly greater in muscles treated with SDF-1α-loaded microparticles than unloaded microparticles or injury alone. Our results indicate that SDF-1α-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. Lay Summary: Following rotator cuff injury, significant muscle degeneration is common and can increase the likelihood of re-tear following surgical treatment. Therefore, we aimed to establish a more pro-healing microenvironment within the muscle following rotator cuff injury by developing an injectable, degradable biomaterial system to deliver stromal cell-derived factor-1alpha (SDF-1α), a protein known to attract pro-healing cell populations. After 7 days, a 4.3× increase in anti-inflammatory, M2-like macrophages (CD11b+CD68+CD163+) and a 3.0× increase in mesenchymal stem cells (CD29+CD44+CD90+) were observed in muscles treated with our SDF-1α-loaded biomaterial, suggesting that our biomaterial system may be a method to shift the cellular composition and create a more pro-regenerative microenvironment within muscle after rotator cuff injury. Future Work Statement: Future work will investigate the ability for SDF-1α-loaded microparticles, which were shown in this work to recruit anti-inflammatory, M2-like macrophages and mesenchymal stem cells to the supraspinatus muscle following rotator cuff injury, to reduce muscle degeneration and improve muscle function after tendon tear. [Figure not available: see fulltext.].