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While the majority of biomaterials are tested using <jats:italic>in vitro<\/jats:italic> cell monocultures, the importance of synergistic interactions between different cell types on paracrine signalling has recently been highlighted. In this proof-of-concept study, we asked whether the first contact of surfaces with whole human blood could steer the tissue healing response. This hypothesis was tested using alkali-treatment of rough titanium (Ti) surfaces since they have clinically been shown to improve early implant integration and stability, yet blood-free <jats:italic>in vitro<\/jats:italic> cell cultures poorly correlated with <jats:italic>in vivo<\/jats:italic> tissue healing. We show that alkali-treatment, compared to native Ti surfaces, increased blood clot thickness, including platelet adhesion. Strikingly, blood clots with entrapped blood cells in synergistic interactions with fibroblasts, but not fibroblasts alone, upregulated the secretion of major factors associated with fast healing. This includes matrix metalloproteinases (MMPs) to break down extracellular matrix and the growth factor VEGF, known for its angiogenic potential. Consequently, <jats:italic>in vitro<\/jats:italic> test platforms, which consider whole blood-implant interactions, might be superior in predicting wound healing in response to biomaterial properties.<\/jats:p>","DOI":"10.1038\/srep21071","type":"journal-article","created":{"date-parts":[[2016,2,17]],"date-time":"2016-02-17T10:23:20Z","timestamp":1455704600000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Synergistic interactions of blood-borne immune cells, fibroblasts and extracellular matrix drive repair in an in vitro peri-implant wound healing model"],"prefix":"10.1038","volume":"6","author":[{"given":"Melanie A","family":"Burkhardt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Waser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Milleret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Gerber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian Y","family":"Emmert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Foolen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P","family":"Hoerstrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falko","family":"Schlottig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viola","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,17]]},"reference":[{"key":"BFsrep21071_CR1","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/nature07039","volume":"453","author":"GC Gurtner","year":"2008","unstructured":"Gurtner, G. 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