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

Abstract

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- κ B. 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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>). The inflammation score in the PLLA/ACP group was lower than that in the PLLA group at 6-months, 12-months, and 24-months (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>), and the fibrosis score was reduced in the PLLA/ACP group than that in the PLLA group at 12-months and 24-months (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>). The expression of MMP-9 and NF- κ B in the PLLA/ACP group was significantly less than that in the PLLA group at 6-months, 12-months, and 24-months (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>). 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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>). Furthermore, the protein expression of IL-1 was significantly lower than that in the PLLA group at 6-months, 12-months, and 24-months (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.01</mml:mn></mml:math>). 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.