Evaluation of Long-Term Inflammatory Responses after Implantation of a Novel Fully Bioabsorbable Scaffold Composed of Poly-L-lactic Acid and Amorphous Calcium Phosphate Nanoparticles

摘要

Objectives. Our previous studies have confirmed the superior biocompatibility of the poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) scaffolds compared to PLLA scaffolds at 1-month. In the present study, the long-term inflammatory responses of PLLA/ACP scaffolds in a porcine coronary model have been explored. Methods. The 24 PLLA scaffolds and 24 PLLA/ACP scaffolds were implanted into the coronary arteries of 24 miniature pigs. Serum levels of ALT, AST, and CRP were measured before operation, as well as 1-month, 6-months, 12-months, and 24-months. The vascular segments were taken for pathomorphological observation. HE staining was used for the inflammatory score and fibrosis score. Immunohistochemical staining detected positive expression indexes of MMP-9 and NF-κB. The expression of inflammation-related proteins of IL-1 and IL-6 was detected by Western Blot in surrounding tissues of scaffolds. Results. There was no significant difference between the two groups in ALT, AST, and UR at different time points (). The inflammation score in the PLLA/ACP group was lower than that in the PLLA group at 6-months, 12-months, and 24-months (), and the fibrosis score was reduced in the PLLA/ACP group than that in the PLLA group at 12-months and 24-months (). The expression of MMP-9 and NF-κB in the PLLA/ACP group was significantly less than that in the PLLA group at 6-months, 12-months, and 24-months (). The protein expression of IL-1 in the PLLA/ACP group was decreased than that in the PLLA group at 12-months and 24-months (). Furthermore, the protein expression of IL-1 was significantly lower than that in the PLLA group at 6-months, 12-months, and 24-months ().Conclusions. The supplement of ACP nanoparticles can effectively reduce the long-term inflammatory reaction caused by PLLA and has good safety and biocompatibility. The novel bioabsorbable PLLA/ACP scaffold provides reliable guidance for the development and clinical application of bioabsorbable scaffolds in the future.