{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T11:50:39Z","timestamp":1791719439535,"version":"4.3.4"},"reference-count":165,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Paracelsus Medical Private University","award":["FMS_B_116.23-KNMS"],"award-info":[{"award-number":["FMS_B_116.23-KNMS"]}]},{"name":"Good Fibration - Targeting Fibrosis to Enhance Regeneration","award":["#20102\/F2400948-FPR"],"award-info":[{"award-number":["#20102\/F2400948-FPR"]}]},{"name":"Good Fibration - Targeting Fibrosis to Enhance Regeneration","award":["Land Salzburg\/WISS2025"],"award-info":[{"award-number":["Land Salzburg\/WISS2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Macrophages and other phagocytic cells are central regulators of tendon immunobiology, orchestrating inflammation, tissue repair, and extracellular matrix (ECM) remodeling in the tendons. They derive from circulating monocytes and resident tendon-specific populations, including tenophages. Macrophage polarization along the M1\/M2 axis exerts a decisive influence on tendon healing trajectories. Activated M1 macrophages promote the early healing phase for debris clearance initiating the reparative cascade. However, their sustained activity leads to inflammation, ECM degradation, impaired healing, tendinopathy, and heterotopic ossification (HO). Conversely, a timed shift toward activated M2 macrophages promotes resolution of inflammation, angiogenesis, ECM deposition, and fibrocartilage formation, whereas excessive or prolonged M2 activity facilitates adhesion formation, fibrosis, scarring and HO. Recent single-cell and spatial profiling studies showed macrophage heterogeneity across tendon compartments, thereby extending the classical M1\/M2 paradigm and underscoring the relevance of macrophages\/resident tendon cell\u2019s interaction in tendon-specific local niches. Mechanobiological stimuli (depending on magnitude, frequency and duration) further modulate macrophage phenotypes and tendon healing. Emerging coculture models and human tendon-on-chip systems provide high-resolution platforms for dissecting these spatiotemporal interactions. Promising therapeutic approaches comprise the application of extracellular vesicles, controlled mechanoloading regimens, and immunomodulatory biomaterials demonstrating potential to induce regenerative macrophage signatures for improved healing outcomes. Notably, platelet-rich plasma (PRP) formulations shape macrophage responses: leukocyte-rich PRP preferentially promotes M1 activity whereas leukocyte-poor PRP supports M2 polarization. Thus, mechano- and immunomodulatory strategies can offer precise control over macrophage dynamics. Regarding the Achilles tendon pathologies, such approaches are helpful by directing macrophage-mediated inflammation towards effective tendon healing outcomes.<\/jats:p>","DOI":"10.3390\/ijms27052130","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:35:17Z","timestamp":1772022917000},"page":"2130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Role of Phagocytic Cells in the Achilles Tendon"],"prefix":"10.3390","volume":"27","author":[{"given":"Yasir","family":"Majeed","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University, Prof.-Ernst-Nathan Stra\u00dfe 1, 90419 Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kokozidou","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University, Prof.-Ernst-Nathan Stra\u00dfe 1, 90419 Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7086-9743","authenticated-orcid":false,"given":"Clemens","family":"G\u00f6gele","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University, Prof.-Ernst-Nathan Stra\u00dfe 1, 90419 Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0220-4766","authenticated-orcid":false,"given":"Andreas","family":"Traweger","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury & Tissue Regeneration Center Salzburg, Institute of Tendon and Bone Regeneration, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Lehner","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury & Tissue Regeneration Center Salzburg, Institute of Tendon and Bone Regeneration, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Tempfer","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury & Tissue Regeneration Center Salzburg, Institute of Tendon and Bone Regeneration, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9807-9532","authenticated-orcid":false,"given":"Gundula Gesine","family":"Schulze-Tanzil","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University, Prof.-Ernst-Nathan Stra\u00dfe 1, 90419 Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e23629","DOI":"10.1096\/fj.202300601RRR","article-title":"Single nucleus and spatial transcriptomic profiling of healthy human hamstring tendon","volume":"38","author":"Mimpen","year":"2024","journal-title":"FASEB J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1136\/annrheumdis-2020-219335","article-title":"Novel self-amplificatory loop between T cells and tenocytes as a driver of chronicity in tendon disease","volume":"80","author":"Cafaro","year":"2021","journal-title":"Ann. 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