scholarly journals Improved Biocompatibility of Novel Biodegradable Scaffold Composed of Poly-L-lactic Acid and Amorphous Calcium Phosphate Nanoparticles in Porcine Coronary Artery

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Dongsheng Gu ◽  
Gaoke Feng ◽  
Guanyang Kang ◽  
Xiaoxin Zheng ◽  
Yuying Bi ◽  
...  

Using poly-L-lactic acid for implantable biodegradable scaffold has potential biocompatibility issue due to its acidic degradation byproducts. We have previously reported that the addition of amorphous calcium phosphate improved poly-L-lactic acid coating biocompatibility. In the present study, poly-L-lactic acid and poly-L-lactic acid/amorphous calcium phosphate scaffolds were implanted in pig coronary arteries for 28 days. At the follow-up angiographic evaluation, no case of stent thrombosis was observed, and the arteries that were stented with the copolymer scaffold had significantly less inflammation and nuclear factor-κB expression and a greater degree of reendothelialization. The serum levels of vascular endothelial growth factor and nitric oxide, as well the expression of endothelial nitric oxide synthase and platelet-endothelial cell adhesion molecule-1, were also significantly higher. In conclusion, the addition of amorphous calcium phosphate to biodegradable poly-L-lactic acid scaffold minimizes the inflammatory response, promotes the growth of endothelial cells, and accelerates the reendothelialization of the stented coronary arteries.

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Gaoke Feng ◽  
Thanh Dinh Nguyen ◽  
Xin Yi ◽  
Yongnan Lyu ◽  
Zhiyuan Lan ◽  
...  

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 (P<0.05). The inflammation score in the PLLA/ACP group was lower than that in the PLLA group at 6-months, 12-months, and 24-months (P<0.05), and the fibrosis score was reduced in the PLLA/ACP group than that in the PLLA group at 12-months and 24-months (P<0.05). 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 (P<0.05). 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 (P<0.05). Furthermore, the protein expression of IL-1 was significantly lower than that in the PLLA group at 6-months, 12-months, and 24-months (P<0.01). 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.


2018 ◽  
Vol 33 (2) ◽  
pp. 227-233 ◽  
Author(s):  
Thanh Dinh Nguyen ◽  
Gaoke Feng ◽  
Xin Yi ◽  
Yongnan Lyu ◽  
Zhiyuan Lan ◽  
...  

Objective Using coronary angiography and intravascular ultrasound methods to evaluate the performance of the novel fully bioabsorbable scaffold (NFBS) composed of poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) at six-month follow-up by comparing with PLLA scaffolds Methods Twelve PLLA/ACP scaffolds and 12 PLLA scaffolds were implanted into the coronary arteries of 12 miniature pigs. Quantitative coronary angiography (QCA) was used to measure the reference vessel diameter (RVD), mean lumen diameter (MLD) and late lumen loss (LLL). According to IVUS images, we calculated the strut malapposition rate (SMR) at post implantation, strut overlap rate (SOR), reference vessel area (RVA), mean stent area (MSA), mean lumen area (MLA) and luminal patency rate (LPR) at six-month follow-up. The radial strength of the scaffold was evaluated using a catheter tensile testing machine. Results QCA results indicated that, at six month, MLD of PLLA/ACP scaffolds was greater than those of PLLA scaffolds (2.47 ± 0.22 mm vs. 2.08 ± 0.25 mm, P < 0.05); LLL of PLLA/ACP scaffolds was less than those of PLLA scaffolds (0.42 ± 0.20 mm vs. 0.75 ± 0.22 mm, P < 0.05). IVUS results showed the SMR and SOR were all significantly less with the PLLA/ACP scaffolds than the PLLA scaffolds (5.84% ± 3.56% vs. 17.72% ± 4.86%, P < 0.05) (6.17% ± 4.63% vs. 17.65% ± 4.29%, P < 0.05). MSA, MLA and LPR of the PLLA/ACP scaffolds were all greater than those of PLLA scaffolds (6.35 ± 0.45 mm2 vs. 5.35 ± 0.51 mm2, P < 0.05) (4.76 ± 0.46 mm2 vs. 3.77 ± 0.46 mm2, P < 0.05) (78.01% ± 12.29% vs. 61.69% ± 9.76%, P < 0.05). Radial strength of PLLA/ACP scaffold at six month was greater than that of PLLA scaffold (76.33 ± 3.14 N vs. 67.67 ± 3.63 N). Conclusion The NFBS had less stent recoil, better lumen patency rate and greater radial strength than PLLA scaffolds. The results suggest the NFBS scaffolds can maintain the structural strength and functional performance, which are effective for up to six months when implanted in porcine coronary arteries.


1995 ◽  
Vol 268 (5) ◽  
pp. H1966-H1972 ◽  
Author(s):  
R. Nakaike ◽  
H. Shimokawa ◽  
H. Yasutake ◽  
H. Sumimoto ◽  
A. Ito ◽  
...  

L-Arginine analogues have been widely used to examine the role of endothelium-derived nitric oxide (NO) in vascular responses; however, the effects of the agents on coronary vasomotion are not fully understood. In this study, we examined the effects of the analogues on vasomotion of isolated porcine coronary arteries. Strips of the porcine coronary artery were suspended for isometric tension recording in Krebs-Henseleit solution. L-Arginine analogues, N omega-nitro-L-arginine methyl ester (L-NAME, 10(-9)-10(-3) M), NG-monomethyl-L-arginine (L-NMMA, 10(-9)-10(-3) M), and NG-nitro-L-arginine (L-NNA, 10(-9)-10(-3) M), caused dose-dependent contractions, which were greater in strips with than in those without endothelium. Those endothelium-dependent contractions were almost abolished by indomethacin (10(-5) M) and FeCl2 (10(-3) M). The latter reduces prostaglandin H2 to 12-heptadecatrienoic acid, which has no vasoconstrictor effect. These results indicate that the L-arginine analogues cause endothelium-dependent contractions that are mediated by prostaglandin endoperoxides and suggest that they have properties other than simple inhibition of NO synthesis in porcine coronary arteries.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Gaoke Feng ◽  
Chaoshi Qin ◽  
Fei Sha ◽  
Yongnan Lyu ◽  
Jinggang Xia ◽  
...  

Purpose. Our previous research has confirmed that the addition of nano-amorphous calcium phosphate (ACP) materials can improve the support of poly-L-lactic acid (PLLA) vascular scaffolds. Based on this, we continued to explore the effect of novel bioresorbable scaffold composed of PLLA and ACP nanoparticles on inflammation and calcification of surrounding tissues after scaffold implantation in porcine coronary artery. Methods. PLLA/ACP scaffolds in the experimental group and PLLA scaffolds in the control group were implanted into the coronary arteries of small pigs. Serum levels of C-reactive protein (CRP), calcium (Ca), and alkaline phosphatase (ALP) were measured before implantation and at 1, 6, 12, and 24 months after operation. Intravascular ultrasonography (IVUS) was performed to evaluate the vascular calcification score. The scaffold and surrounding tissues were hematoxylin-eosin staining for inflammation score. The scaffold and surrounding tissues were stained with NF-κB and ALP, and the positive expression index was calculated. Western blot was used to detect the expression of IL-6 and BMP-2 in the tissues around the scaffold. Results. There was no statistically significant difference between the two groups in CRP, calcium, and ALP at preimplant, 1 month, 6 months, 12 months, and 24 months ( P > 0.05 ). The inflammation score, NF-κB positive expression index, and calcification score in the PLLA/ACP group were lower than that in the PLLA group at 12 months and 24 months ( P < 0   05 ). The ALP positive expression index in the PLLA/ACP group was lower than that in the PLLA group at 6 months, 12 months, and 24 months ( P < 0   05 ). Western blot results showed that the IL-6 expression level in the PLLA/ACP group was significantly lower than that in the control group at 6 months, 12 months, and 24 months ( P < 0.05 ). The expression of BMP-2 in the PLLA/ACP group was significantly lower than that in the control group at 12 months and 24 months ( P < 0.05 ). Conclusion. The PLLA/ACP composite scaffold has good biocompatibility. The incorporation of nanoscale ACP can reduce the inflammatory response caused by the acid metabolites of PLLA scaffolds, reduce the expression of procalcification factors in the body, and inhibit tissue calcification. The PLLA/ACP composite scaffold provides reliable guidance for the application and development of degradable vascular scaffold.


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