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An in\u00a0vitro model of the supraspinatus and subacromial bursa was created and treated with control, platelet\u2010rich plasma (PRP), autologous activated serum (AAS), or a combination of PRP+AAS. The effect of treatment on macrophage polarization between M1 proinflammatory macrophages or M2 anti\u2010inflammatory macrophages was measured using gene expression, protein expression, flow cytometry, and nitric oxide production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tendon and bursa treated with PRP, AAS, and PRP+AAS significantly decreased the gene expression of M1 markers interleukin (IL)\u201012 and tumor necrosis factor\u2010alpha while significantly increasing the expression of M2 markers arginase, IL\u201010, and transforming growth factor\u2010\u03b2 (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .05) compared with treatment with control. Enzyme\u2010linked immunosorbent assay analysis of protein production demonstrated that, compared with control, coculture treated with PRP, AAS, and PRP+AAS significantly decreased markers of M1\u2010macrophages (IL\u20106, IL\u201012, and tumor necrosis factor\u2010alpha) while significantly increasing the expression of markers of M2\u2010macrophages (arginase, IL\u201010, and transforming growth factor\u2010beta) (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .05). Flow cytometry analysis of surface markers demonstrated that compared with control, tendon and bursa treated with PRP, AAS, and PRP+AAS significantly decreased markers of M1\u2010macrophages (CD80, CD86, CD64, CD16) while significantly increasing the expression of markers of M2\u2010macrophages (CD163 and CD206) (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .05). Treatment of the coculture with PRP, AAS, and PRP+AAS consistently demonstrated a decrease in nitric oxide production (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .05) compared with control. AAS and PRP+AAS demonstrated an increased macrophage shift to M2 compared with PRP alone, whereas there was not as uniform of a shift when comparing PRP+AAS with AAS alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In an in\u00a0vitro model of rotator cuff tears, the treatment of supraspinatus tendon and subacromial bursa with PRP, AAS, and PRP+AAS demonstrated an increase in markers of anti\u2010inflammatory M2\u2010macrophages and a concomitant decrease in markers of proinflammatory M1\u2010macrophages. AAS and PRP+AAS contributed to a large shift to macrophage polarization to the anti\u2010inflammatory M2 compared with PRP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance<\/jats:title>\n                    <jats:p>The mechanism of biologic adjuvant effects on the rotator cuff remains poorly understood. This study suggests that they may contribute to polarization of macrophages for their proinflammatory (M1) state to the anti\u2010inflammatory (M2) state.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.arthro.2024.04.031","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T01:27:20Z","timestamp":1715390840000},"page":"32-41","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"title":["Biologic Adjuvants to Rotator Cuff Repairs Induce Anti\u2010inflammatory Macrophage 2 Polarization and Reduce Inflammatory Macrophage 1 Polarization In\u00a0Vitro"],"prefix":"10.1002","volume":"41","author":[{"given":"Benjamin C.","family":"Hawthorne","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery UConn Health Farmington Connecticut U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery UConn Health Farmington Connecticut U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Beth R.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Cote","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustus D.","family":"Mazzocca","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Coyner","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery UConn Health Farmington Connecticut 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