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

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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.

SDF-1α-loaded heparin-based microparticles, delivered via intra-muscular injection, may be a promising method to create a more pro-regenerative cellular milieu following severe rotator cuff injury.

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References

  1. Brzoska E, Kowalewska M, Markowska-Zagrajek A, Kowalski K, Archacka K, Zimowska M, et al. Sdf-1 (CXCL12) improves skeletal muscle regeneration via the mobilisation of Cxcr4 and CD34 expressing cells. Biol Cell. 2012;104(12):722–37. https://doi.org/10.1111/boc.201200022.

    Article  Google Scholar 

  2. Bleul CC, Fuhlbrigge RC, Casanovas JM, Aiuti A, Springer TA. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med. 1996;184:1101–9. https://doi.org/10.1084/jem.184.3.1101.

    Article  Google Scholar 

  3. D’Apuzzo M, Rolink A, Loetscher M, Hoxie JA, Clark-Lewis I, Melchers F, et al. The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4. Eur J Immunol. 1997;27:1788–93. https://doi.org/10.1002/eji.1830270729.

    Article  Google Scholar 

  4. Aiuti BA, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos, JC. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med. 1997;185(1):111–20. https://doi.org/10.1084/jem.185.1.111.

    Article  Google Scholar 

  5. Cross DP, Wang C. Stromal-derived factor-1 alpha-loaded PLGA microspheres for stem cell recruitment. Pharm Res. 2011;28(10):2477–89. https://doi.org/10.1007/s11095-011-0474-x.

    Article  Google Scholar 

  6. Otsuru S, Tamai K, Yamazaki T, Yoshikawa H, Kaneda Y. Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cell-derived factor-1 pathway. Stem Cells. 2008;26(1):223–34. https://doi.org/10.1634/stemcells.2007-0515.

    Article  Google Scholar 

  7. Anderson EM, Kwee BJ, Lewin SA, Raimondo T, Manav M, Mooney DJ. Local delivery of VEGF and SDF enhances endothelial progenitor cell recruitment and resultant recovery from ischemia. Tissue Eng Part A. 2015;21(7–8):1217–27. https://doi.org/10.1089/ten.tea.2014.0508.

    Article  Google Scholar 

  8. Kucia M, Jankowski K, Reca R, Wysoczynski M, Bandura L, Allendorf DJ, et al. CXCR4–SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol. 2004;35:233–45.

    Article  Google Scholar 

  9. Zhao W, Jin K, Li J, Qiu X, Li S. Delivery of stromal cell-derived factor 1α for in situ tissue regeneration. J Biol Eng. 2017;11:22. https://doi.org/10.1186/s13036-017-0058-3.

    Article  Google Scholar 

  10. Krieger JR, Ogle ME, McFaline-Figueroa J, Segar CE, Temenoff JS, Botchwey EA. Spatially localized recruitment of anti-inflammatory monocytes by SDF-1α-releasing hydrogels enhances microvascular network remodeling. Biomaterials. 2016;77:280–90. https://doi.org/10.1016/j.biomaterials.2015.10.045.

    Article  Google Scholar 

  11. Ogle ME, Krieger JR, Tellier LE, McFaline-Figueroa J, Temenoff JS, Botchwey EA. Dual affinity heparin-based hydrogels achieve pro-regenerative immunomodulation and microvascularremodeling. ACS Biomater Sci Eng. 2017; https://doi.org/10.1021/acsbiomaterials.6b00706.

  12. Gladstone JN, Bishop JY, Lo IKY, Flatow EL. Fatty infiltration and atrophy of the rotator cuff do not improve after rotator cuff repair and correlate with poor functional outcomes. Am J Sports Med. 2007;35(5):719–28. https://doi.org/10.1177/0363546506297539.

    Article  Google Scholar 

  13. Gerber C, Fuchs B, Hodler J. The results of repair of massive tears of the rotator cuff. J Bone Joint Surg Am. 2000;82(4):505–15.

    Article  Google Scholar 

  14. Gumucio JP, Davis ME, Bradley JR, Stafford PL, Schiffman CJ, Lynch EB, et al. Rotator cuff tear reduces muscle fiber specific force production and induces macrophage accumulation and autophagy. J Orthop Res. 2012;30(12):1963–70. https://doi.org/10.1002/jor.22168.

    Article  Google Scholar 

  15. Gumucio J, Flood M, Harning J, Phan A, Roche S, Lynch E, et al. T lymphocytes are not required for the development of fatty degeneration after rotator cuff tear. Bone Joint Res. 2014;3(9):262–72. https://doi.org/10.1302/2046-3758.39.2000294.

    Article  Google Scholar 

  16. Mendias CL, Roche SM, Harning JA, Davis ME, Lynch EB, Enselman ERS, et al. Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears. J Shoulder Elb Surg. 2015;24(1):111–9. https://doi.org/10.1016/j.jse.2014.06.037.

    Article  Google Scholar 

  17. Krieger JR, Tellier LE, Ollukaren MT, Temenoff JS, Botchwey EA. Quantitative analysis of immune cell subset infiltration of supraspinatus muscle after severe rotator cuff injury. Regen Eng Transl Med. 2017;3(2):82–93. https://doi.org/10.1007/s40883-017-0030-2.

    Article  Google Scholar 

  18. Tellier LE, Miller T, McDevitt TC, Temenoff JS. Hydrolysis and sulfation pattern effects on release of bioactive bone morphogenetic protein-2 from heparin-based microparticles. J Mater Chem B. 2015;3(40):8001–9. https://doi.org/10.1039/C5TB00933B.

    Article  Google Scholar 

  19. Peng Y, Tellier LE, Temenoff JS. Heparin-based hydrogels with tunable sulfation & degradation for anti-inflammatory small molecule delivery. Biomater Sci. 2016;4(9):1371–80. https://doi.org/10.1039/C6BM00455E.

    Article  Google Scholar 

  20. Sadir R, Imberty A, Baleux F, Lortat-Jacob H. Heparan sulfate/heparin oligosaccharides protect stromal cell-derived factor-1 (SDF-1)/CXCL12 against proteolysis induced by CD26/dipeptidyl peptidase IV. J Biol Chem. 2004;279(42):43854–60. https://doi.org/10.1074/jbc.M405392200.

    Article  Google Scholar 

  21. Purcell BP, Elser JA, Mu A, Margulies KB, Burdick JA. Synergistic effects of SDF-1alpha chemokine and hyaluronic acid release from degradable hydrogels on directing bone marrow derived cell homing to the myocardium. Biomaterials. 2012;33(31):7849–57. https://doi.org/10.1016/j.biomaterials.2012.07.005.

    Article  Google Scholar 

  22. Roy S, Lai H, Zouaoui R, Duffner J, Zhou H, Jayaraman LP, et al. Bioactivity screening of partially desulfated low-molecular-weight heparins: a structure/activity relationship study. Glycobiology. 2011;21(9):1194–205. https://doi.org/10.1093/glycob/cwr053.

    Article  Google Scholar 

  23. Prokoph S, Chavakis E, Levental KR, Zieris A, Freudenberg U, Dimmeler S, et al. Sustained delivery of SDF-1a from heparin-based hydrogels to attract circulating pro-angiogenic cells. Biomaterials. 2012;33(19):4792–800. https://doi.org/10.1016/j.biomaterials.2012.03.039.

    Article  Google Scholar 

  24. Rinker TE, Philbrick BD, Temenoff JS. Core-shell microparticles for protein sequestration and controlled release of a protein-laden core. Acta Biomater. 2017;56(1):91–101. https://doi.org/10.1016/j.actbio.2016.12.042.

    Article  Google Scholar 

  25. Hettiaratchi MH, Miller T, Temenoff JS, Guldberg RE, McDevitt TC. Heparin microparticles effects on presentation and bioactivity of bone morphogenetic protein-2. Biomaterials. 2014;35(25):7228–38. https://doi.org/10.1016/j.biomaterials.2014.05.011.

    Article  Google Scholar 

  26. Xu X, Jha AK, Duncan RL, Jia X. Heparin-decorated, hyaluronic acid-based hydrogel particles for the controlled release of bone morphogenetic protein 2. Acta Biomater. 2011;7(8):3050–9. https://doi.org/10.1016/j.actbio.2011.04.018.

    Article  Google Scholar 

  27. Hennink WE, van Nostrum CF. Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev. 2012;64:223–36. https://doi.org/10.1016/j.addr.2012.09.009.

    Article  Google Scholar 

  28. Doroski DM, Levenston ME, Temenoff JS. Cyclic tensile culture promotes fibroblastic differentiation of marrow stromal cells encapsulated in poly(ethylene glycol)-based hydrogels. Tissue Eng Part A. 2010;16(11):3457–66. https://doi.org/10.1089/ten.tea.2010.0233.

    Article  Google Scholar 

  29. Qiu Y, Lim JJ, Scott L, Adams RC, Bui HT, Temenoff JS. PEG-based hydrogels with tunable degradation characteristics to control delivery of marrow stromal cells for tendon overuse injuries. Acta Biomater. 2011;7(3):959–66. https://doi.org/10.1016/j.actbio.2010.11.002.

    Article  Google Scholar 

  30. Van De Wetering P, Metters AT, Schoenmakers RG, Hubbell JA. Poly(ethylene glycol) hydrogels formed by conjugate addition with controllable swelling, degradation, and release of pharmaceutically active proteins. J Control Release. 2005;102(3):619–27. https://doi.org/10.1016/j.jconrel.2004.10.029.

    Article  Google Scholar 

  31. Liu X, Manzano G, Kim HT, Feeley BT. A rat model of massive rotator cuff tears. J Orthop Res. 2011;29:588–95. https://doi.org/10.1002/jor.21266.

    Article  Google Scholar 

  32. Gimbel JA, Van Kleunen JP, Mehta S, Perry SM, Williams GR, Soslowsky LJ. Supraspinatus tendon organizational and mechanical properties in a chronic rotator cuff tear animal model. J Biomech. 2004;37:739–49. https://doi.org/10.1016/j.jbiomech.2003.09.019.

    Article  Google Scholar 

  33. Seto SP, Miller T, Temenoff JS. Effect of selective heparin desulfation on preservation of bone morphogenetic protein-2 bioactivity after thermal stress. Bioconjug Chem. 2015;26(2):286–93. https://doi.org/10.1021/bc500565x.

    Article  Google Scholar 

  34. Inoue Y, Nagasawa K. Selective N-desulfation of heparin with dimethyl sulfoxide containing water or methanol. Carbohydr Res. 1976;46:87–95. https://doi.org/10.1016/S0008-6215(00)83533-8.

    Article  Google Scholar 

  35. Nagasawa K, Inoue Y, Kamata T. Solvolytic desulfation of glycosaminoglycuronan sulfates with dimethyl sulfoxide containing water or methanol. Carbohydr Res. 1977;58:47–55. https://doi.org/10.1016/S0008-6215(00)83402-3.

    Article  Google Scholar 

  36. Tellier LE, Trevino EA, Brimeyer AL, Reece DR, Willett NJ, Guldberg RE, et al. Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis. Biomater Sci. 2018. https://doi.org/10.1039/C8BM00010G.

  37. Ogle ME, Segar CE, Sridhar S, Botchwey EA. Monocytes and macrophages in tissue repair: implications for immunoregenerative biomaterial design. Exp Biol Med. 2016;241(10):1084–97. https://doi.org/10.1177/1535370216650293.

    Article  Google Scholar 

  38. Badylak SF, Valentin JE, Ravindra AK, McCabe GP, Stewart-Akers AM. Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng Part A. 2008;14(11):1835–42. https://doi.org/10.1089/ten.tea.2007.0264.

    Article  Google Scholar 

  39. Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells: Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther. 2007;9(1):204. https://doi.org/10.1186/ar2116.

    Article  Google Scholar 

  40. Kreuger J, Phillipson M. Targeting vascular and leukocyte communication in angiogenesis, inflammation and fibrosis. Nat Rev Drug Discov. 2016;15(2):125–42. https://doi.org/10.1038/nrd.2015.2.

    Article  Google Scholar 

  41. Hudalla GA, Eng TS, Murphy WL. An approach to modulate degradation and mesenchymal stem cell behavior in poly(ethylene glycol) networks. Biomacromolecules. 2008;9(3):842–49. https://doi.org/10.1021/bm701179s.

    Article  Google Scholar 

  42. Held KD, Melder DC. Toxicity of the sulfhydryl-containing radioprotector dithiothreitol. Radiat Res Soc. 1987;112(3):544–54. 

    Article  Google Scholar 

  43. Browning MB, Cereceres SN, Luong PT, Cosgriff-Hernandez EM. Determination of the in vivo degradation mechanism of PEGDA hydrogels. J Biomed Res A. 2014;102(12):4244–51. https://doi.org/10.1002/jbm.a.35096.

    Google Scholar 

  44. Christenson EM, Dadsetan M, Wiggins M, Anderson JM, Hiltner A. Poly(carbonate urethane) and poly(ether urethane) biodegradation: in vivo studies. J Biomed Mater Res A. 2004;69A(3):407–16. https://doi.org/10.1002/jbm.a.30002.

    Article  Google Scholar 

  45. Xu H, Deng Y, Chen D, Hong W, Lu Y, Dong X. Esterase-catalyzed dePEGylation of pH-sensitive vesicles modified with cleavable PEG-lipid derivatives. J Control Release. 2008;130(3):238–45. https://doi.org/10.1016/j.jconrel.2008.05.009.

    Article  Google Scholar 

  46. Zamani M, Prabhakaran MP, Thian ES, Ramakrishna S. Controlled delivery of stromal derived factor-1alpha from poly lactic-co-glycolic acid core-shell particles to recruit mesenchymal stem cells for cardiac regeneration. J Colloid Interface Sci. 2015;451:144–52. https://doi.org/10.1016/j.jcis.2015.04.005.

    Article  Google Scholar 

  47. Sakiyama-Elbert SE, Hubbell JA. Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix. J Control Release. 2000;69(1):149–58. https://doi.org/10.1016/S0168-3659(00)00296-0.

    Article  Google Scholar 

  48. Yang J, Zhang L, Yu C, Yang XF, Wang H. Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases. Biomark Res. 2014;2(1):1. https://doi.org/10.1186/2050-7771-2-1.

    Article  Google Scholar 

  49. McCullough KC, Basta S, Knotig S, Gerber H, Schaffner R, Kim YB, et al. Intermediate stages in monocyte–macrophage differentiation modulate phenotype and susceptibility to virus infection. Immunology. 1999;98(2):203–12. https://doi.org/10.1046/j.1365-2567.1999.00867.x.

    Article  Google Scholar 

  50. Olingy CE, San Emeterio CL, Ogle ME, Krieger JR, Bruce AC, Pfau DD, et al. Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury. Sci Rep. 2017;7(1):447. https://doi.org/10.1038/s41598-017-00477-1.

    Article  Google Scholar 

  51. Gupta SK, Pillarisetti K, Lysko PG. Modulation of CXCR4 expression and SDF-1 α functional activity during differentiation of human monocytes and macrophages. J Leukoc Biol. 1999;66:135–43. https://doi.org/10.1002/jlb.66.1.135.

    Article  Google Scholar 

  52. Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol Integr Comp Physiol. 2005;288:345–53. https://doi.org/10.1152/ajpregu.00454.2004.

    Article  Google Scholar 

  53. Chazaud B, Brigitte M, Yacoub-Youssef H, Arnold L, Gherardi R, Sonnet C, et al. Dual and beneficial roles of macrophages during skeletal muscle regeneration. Exerc Sport Sci Rev. 2009;37(1):18–22. https://doi.org/10.1097/JES.0b013e318190ebdb.

    Article  Google Scholar 

  54. Merly F, Lescaudron L, Rouaud T, Crossin F, Gardahaut MF. Macrophages enhnace muscle satellite cell proliferation and delay their differentiation. Muscle Nerve. 1999;22(6):724–32. https://doi.org/10.1002/(SICI)1097-4598(199906)22:6<724::AID-MUS9>3.0.CO;2-O.

    Article  Google Scholar 

  55. Peng H, Huard J. Muscle-derived stem cells for musculoskeletal tissue regeneration and repair. Transpl Immunol. 2004;12(3–4):311–9. https://doi.org/10.1016/j.trim.2003.12.009.

    Article  Google Scholar 

  56. Dezawa M, Ishikawa H, Itokazu Y, Yoshihara T, Hoshino M, Takeda S, et al. Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science. 2005;309(5732):314–7. https://doi.org/10.1126/science.1110364.

    Article  Google Scholar 

  57. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 2004;109(12):1543-9. https://doi.org/10.1161/01.CIR.0000124062.31102.57.

    Article  Google Scholar 

  58. Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol. 2012;12(5):383–96. https://doi.org/10.1038/nri3209.

    Article  Google Scholar 

  59. Winkler IG, Sims NA, Pettit AR, Barbier V, Nowlan B, Helwani F, Poulton IJ, et al. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood 2010;116(23):4815–28. https://doi.org/10.1182/blood-2009-11-253534.

  60. Petit I, Jin D, Rafii S. The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. Trends Immunol. 2007;28(7):299–307. https://doi.org/10.1016/j.it.2007.05.007.

    Article  Google Scholar 

  61. Schirmer SH, van Nooijen FC, Piek JJ, van Royen N. Stimulation of collateral artery growth: travelling further down the road to clinical application. Heart. 2009;95(3):191–7. https://doi.org/10.1136/hrt.2007.136119.

    Article  Google Scholar 

  62. Van Royen N, Voskuil M, Hoefer I, Jost M, De Graaf S, Hedwig F, et al. CD44 regulates arteriogenesiss in mice and is differentially expressed in patients with poor and good collateralization. Circulation. 2004;109(13):1647–52. https://doi.org/10.1161/01.CIR.0000124066.35200.18.

    Article  Google Scholar 

  63. Tobe T, Okamoto N, Vinores MA, Derevjanik NL, Vinores SA, Zack DJ, et al. Evolution of neovascularization in mice with overexpression of vascular endothelial growth factor in photoreceptors. Invest Ophthalmol Vis Sci. 1998;39(1):180–8.

    Google Scholar 

  64. Jung S, Kleinheinz J. Angiogenesis—the key to regeneration. Regen Med Tissue Eng - Chapter 19. 2013:453–473. https://doi.org/10.5772/46192.

  65. Borselli C, Storrie H, Benesch-Lee F, Shvartsman D, Cezar C, Lichtman JW, et al. Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors. Proc Natl Acad Sci U S A. 2010;107(8):3287–92. https://doi.org/10.1073/pnas.0903875106.

    Article  Google Scholar 

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Acknowledgements

We would like to acknowledge the Petit Institute Core Facilities (Histology, Confocal Microscopy, and Flow Cytometry) for their services and shared resources that enabled us to produce this publication.

Funding

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 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). This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This research was also supported by a Georgia Tech/Emory University Immunoengineering Center Seed Grant and an Emory Department of Orthopaedics Seed Grant.

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Authors and Affiliations

  1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA

    L. E. Tellier, J. R. Krieger, A. L. Brimeyer, A. C. Coogan, A. A. Falis, T. E. Rinker, S. N. Thomas, N. J. Willett, E. A. Botchwey & J. S. Temenoff

  2. School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    A. Schudel

  3. Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA

    A. Schudel, S. N. Thomas, N. J. Willett, E. A. Botchwey & J. S. Temenoff

  4. George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    S. N. Thomas

  5. Winship Cancer Institute, Emory University, Decatur, GA, USA

    S. N. Thomas

  6. Wilmington Health Orthopedic Medical Center, Wilmington, NC, USA

    C. D. Jarrett

  7. Department of Orthopedics, Emory University, Decatur, GA, USA

    C. D. Jarrett & N. J. Willett

  8. Atlanta Veteran’s Affairs Medical Center, Decatur, GA, USA

    N. J. Willett

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  1. L. E. Tellier
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Correspondence to J. S. Temenoff.

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Tellier, L.E., Krieger, J.R., Brimeyer, A.L. et al. Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury. Regen. Eng. Transl. Med. 4, 92–103 (2018). https://doi.org/10.1007/s40883-018-0052-4

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