Optimizing the Biocompatibility of PLLA Stent Materials: Strategy with Biomimetic Coating

Abstract

Background: Poly-L-lactic acid (PLLA) stents have broad application prospects in the treatment of cardiovascular diseases due to their excellent mechanical properties and biodegradability. However, foreign body reactions caused by stent implantation remain a bottleneck that limits the clinical application of PLLA stents. To solve this problem, the biocompatibility of PLLA stents must be urgently improved. Albumin, the most abundant inert protein in the blood, possesses the ability to modify the surface of biomaterials, mitigating foreign body reactions-a phenomenon described as the "stealth effect". In recent years, a strategy based on albumin camouflage has become a focal point in nanomedicine delivery and tissue engineering research. Therefore, albumin surface modification is anticipated to enhance the surface biological characteristics required for vascular stents. However, the therapeutic applicability of this modification has not been fully explored.

Methods: Herein, a bionic albumin (PDA-BSA) coating was constructed on the surface of PLLA by a mussel-inspired surface modification technique using polydopamine (PDA) to enhance the immobilization of bovine serum albumin (BSA).

Results: Surface characterization revealed that the PDA-BSA coating was successfully constructed on the surface of PLLA materials, significantly improving their hydrophilicity. Furthermore, in vivo and in vitro studies demonstrated that this PDA-BSA coating enhanced the anticoagulant properties and pro-endothelialization effects of the PLLA material surface while inhibiting the inflammatory response and neointimal hyperplasia at the implantation site.

Conclusion: These findings suggest that the PDA-BSA coating provides a multifunctional biointerface for PLLA stent materials, markedly improving their biocompatibility. Further research into the diverse applications of this coating in vascular implants is warranted.

Keywords: Poly-L-lactic acid; albumin; biomimetic coating; stealth effect; vascular stent.

Graphical abstract

Figure 1

Preparation of a PDA-BSA coating on the surface of PLLA material. A thin polydopamine layer was coated on the PLLA substrate by immersing the PLLA substrate in an aqueous dopamine solution for a period. And then BSA was covalently grafted onto the resultant PLLA/PDA composite membranes by the coupling between o-benzoquinone and BSA amine.

Figure 2

Surface characterization analysis. ATR-FTIR spectra (A) and XPS spectra (B) and 2D and 3D AFM images (C) and SEM images (D) of the PLLA, PLLA/PDA and PLLA/PDA-BSA samples. (E) EDS mapping images of C, N, O, and S elements on the PLLA/PDA-BSA surface. (F) Water contact angle of the samples (mean ± SD, n = 3).

Figure 3

CD31 and DAPI fluorescence staining images (A) and relative fluorescence intensities indicating cell viability (B) and CD31 expression (C) in ECs after 4 h and 3 days on PLLA, PLLA/PDA and PLLA/PDA-BSA samples (n = 3, *p < 0.05, **p < 0.01, ***p < 0.001).

Figure 4

Assessment of the inflammatory response. (A) Light microscopy images of macrophages adhering to PLLA, PLLA/PDA, and PLLA/PDA-BSA samples for 3 days; (B) ELISA analysis of 3 days TNF-α levels in macrophages from each group. (C) H&E staining of the samples 28 days after subcutaneous implantation (M represents the sample implantation location). (D) Thickness of the fiber capsule on the surface of subcutaneously implanted samples (n = 3, *p < 0.05, **p < 0.01, ***p < 0.001).

Figure 5

(A) SEM images of platelet adhesion on PLLA, PLLA/PDA and PLLA/PDA-BSA surfaces. (B) Platelet adhesion on the samples was determined by LDH assay. (C) Hemolysis rates of different samples (n = 3, *p < 0.05, ***p < 0.001).

Figure 6

(A) Schematic of the in vitro blood circulation model in rabbits. (B) Photographs showing the cross-sections of ducts containing PLLA, PLLA/PDA and PLLA/PDA-BSA films. (C) Photographs showing thrombus formation on the samples. (D) SEM image of a thrombus on the surface of the film. (E) Observation rate of the pipe. (F) Weights of thrombi on the surface of the sample. (G) Blood flow rates in different circuits at the end of extracorporeal circulation (n = 3, ***p < 0.001).

Figure 7

Typical MRI (MSME-PD-T2 sequences) and H&E, anti-CD31 antibody, anti-α-SMA antibody, and anti-OPN antibody staining images of the carotid arteries of Sprague‒Dawley (SD) rats implanted with PLLA, PLLA/PDA, or PLLA/PDA-BSA monofilaments for 28 days. (White arrows in red boxes in MRI vessel wall images indicate proliferative tissue; red bidirectional arrows in H&E-stained images represent the thickness of the neointimal hyperplasia; red unidirectional arrows in anti-CD31 antibody-stained images indicate the endothelial layer of the neointimal hyperplasia; and red *Marks the location of each implanted sample.).