Reduction of fibrous encapsulation by polyethylene glycol-grafted liposomes containing phosphatidylserine

Abstract

Biomedical implants tend to induce fibrous encapsulation which can cause malfunction of devices and local discomfort of patients. The purpose of this study was to reduce foreign body-induced fibrous capsule formation by immunomodulation of macrophages. Polyethylene-glycol-grafted liposomes containing phosphatidylserine (PEG-PSLs) were used to modulate macrophages. Mixed cellulose ester (MCE) membranes coated with a PEG-PSLs-entrapped alginate-gelatin matrix were subcutaneously implanted into rats, and the thickness of the fibrous capsule around each MCE membrane was analyzed after four weeks. PEG-PSLs significantly reduced fibrous capsule thickness, while liposomes containing phosphatidylserine (PSLs) did not affect fibrosis. In in vitro assays, PEG-PSLs suppressed TGF-β1 secretion and multinucleated giant cell (MGC) formation in IL-4-treated RAW 264.7, a murine macrophage cell line. Although PSLs inhibited MGC formation, they exerted no effect on the secretion of TGF- β1, which is known to be an important factor in tissue fibrosis. Therefore, our results suggest that PEG-PSLs reduce fibrous capsule formation by mediating the suppression of TGF-β1 secretion from macrophages.