Releasable, Immune-Instructive, Bioinspired Multilayer Coating Resists Implant-Induced Fibrosis while Accelerating Tissue Repair

Implantable biomaterials trigger foreign body reactions (FBRs), which reduces the functional life of medical devices and prevents effective tissue regeneration. Although existing therapeutic approaches can circumvent collagen-rich fibrotic encapsulation secondary to FBRs, they disrupt native tissue repair. Herein, a new surface engineering strategy in which an apoptotic-mimetic, immunomodulatory, phosphatidylserine liposome (PSL) is released from an implant coating to induce the formation of a macrophage phenotype that mitigates FBRs and improves tissue healing is described. PSL-multilayers constructed on implant surfaces via the layer-by-layer method release PSLs over a 1-month period. In rat muscles, poly(etheretherketone) (PEEK), a nondegradable polymer implant model, induces FBRs with dense fibrotic scarring under an aberrant cellular profile that recruits high levels of inflammatory infiltrates, foreign body giant cells (FBGCs), scar-forming myofibroblasts, and inflammatory M1-like macrophages but negligible amounts of anti-inflammatory M2-like phenotypes. However, the PSL-multilayer coating markedly diminishes these detrimental signatures by shifting the macrophage phenotype. Unlike other therapeutics, PSL-multilayered coatings also stimulate muscle regeneration. This study demonstrates that PSL-multilayered coatings are effective in eliminating FBRs and promoting regeneration, hence offering potent and broad applications for implantable biomaterials. Implanted materials face encapsulation and eventual rejection in a dense, fibrotic scar because they inevitably trigger foreign body reactions (FBRs) of the immune system. A multilayered coating comprising phosphatidylserine liposomes (PSLs), artificial apoptotic mimetics, mitigates FBRs, chronic inflammation, multinucleated giant cell formation, and eventual fibrotic scarring associated with implanted devices while promoting tissue repair through M1-to-M2 macrophage transition.image

Automated summary

"A new surface engineering strategy is described, which involves the release of phosphatidylserine liposomes (PSLs) from an implant coating to modify macrophage phenotype and mitigate foreign body reactions (FBRs), resulting in improved tissue healing. Unlike other therapeutic approaches, PSL-multilayered coatings also promote muscle regeneration."