AUTHOR=Einarsson Halldór Bjarki , Mortensen Anders Frisk , Nielsen Morten Schallburg , Chen Menglin , Nielsen Søren Roesgaard , Kraft David Christian Evar , Jensen Jonas , Bjerre Mette , Andersen Morten Nørregaard , Nygaard Jens Vinge , Bünger Cody Eric , Vorup-Jensen Thomas TITLE=Osteoclast-like multinucleated giant cells reinforce polycaprolactone grafts JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1572238 DOI=10.3389/fimmu.2025.1572238 ISSN=1664-3224 ABSTRACT=Successful application of advanced engineered materials in osteoplasty requires a biological understanding of the recipient reaction. The immune system acts like a double-edged sword by maintaining targeted tissue and rejecting grafts. Nevertheless, even for promising graft materials such as polycaprolactone, insights on contact with immune cells have been restricted due to lacking quantitative assays. Here, we show that polycaprolactone graft sites after cranioplasty are dominated by an immature type of multinucleated giant cells, probably derived from transmigrating peripheral monocytes. The cells interact with the polycaprolactone through extensive pseudopodia formation and localized polymer dissolution. Dynamic mechanical analysis revealed osteoclast-like cells, derived in vitro from primary human monocytes, reinforce polycaprolactone by depositing a CD18 integrin-rich attachment matrix. Our findings give a new perspective on immune cells’ beneficial and detrimental functions in graft lesions, guiding therapy with better graft designs.