Wear particle-induced
inflammation is considered to be the major cause of aseptic implant loosening and clinical failure after
total joint replacement. Due to the frequent absence of symptoms, early detection and intervention prior to implant failure presents a significant challenge. To address this issue, a
N-(2-hydroxypropyl)methacrylamide (
HPMA) copolymer-based optical imaging
contrast agent (P-IRDye) was developed and used for the detection of wear particle-induced
inflammation employing a murine calvaria
osteolysis model. The particle-induced
osteolysis of calvaria was evaluated by H&E,
tartrate-resistant acid phosphatase (TRAP) staining and μ-CT after necropsy. One-day post particle implantation, P-IRDye was administrated to the mice via tail vein injection. Live imaging of the animals 6 days after implantation revealed the preferential distribution and sustained retention of the macromolecular
contrast agent at the site of particle implantation. Immunohistochemical staining and FACS analyses of the calvaria-associated soft tissue revealed extensive uptake of the
HPMA copolymer by F4/80, Ly-6G (Gr1) and CD11c positive cells, which accounts for the retention of the macromolecular probes at the inflammatory sites. To test the potential of the system for therapeutic intervention, an
acid-labile
HPMA copolymer-
dexamethasone conjugate (P-Dex) was prepared and shown to prevent the particle-induced
inflammation and bone damage in the calvaria
osteolysis model.