Polydopamine (PDA) coatings with endothelial vascular growth factor (VEGF) immobilization inhibiting neointimal formation post zinc (zn) wire implantation in rat aortas

Abstract

Background Bioresorbable stents are designed to provide temporary mechanical support to the coronary arteries and then slowly degrade in vivo to avoid chronic inflammation. Zinc (Zn) is a promising material for bioresorbable stents; However, it can cause inflammation and neointimal formation after being implanted into blood vessels. Methods To improve biocompatibility of Zn, we first coated it with polydopamine (PDA), followed by immobilization of endothelial vascular growth factor (VEGF) onto the PDA coatings. Adhesion, proliferation, and phenotype maintenance of endothelial cells (ECs) on the coated Zn were evaluated in vitro. Then, a wire aortic implantation model in rats mimicking endovascular stent implantation in humans was used to assess vascular responses to the coated Zn wires in vivo. Thrombosis in aortas post Zn wire implantation, degradation of Zn wires in vivo, neointimal formation surrounding Zn wires, and macrophage infiltration and extracellular matrix (ECM) remodeling in the neointimas were examined. Results In vitro data showed that the PDA-coated Zn encouraged EC adhesion, spreading, proliferation, and phenotype maintenance on its surfaces. VEGF functionalization on PDA coatings further enhanced the biocompatibility of Zn to ECs. Implantation of PDA-coated Zn wires into rat aortas didn’t cause thrombosis and showed a faster blood flow than pure Zn or the Zn wires coated with VEGF alone. In addition, the PDA coating didn’t affect the degradation of Zn wires in vivo. Besides, the PDA-coated Zn wires reduced neointimal formation, increased EC coverage, decreased macrophage infiltration, and declined aggrecan accumulation in ECM. VEGF immobilization onto PDA coatings didn’t cause thrombosis and affect Zn degradation in vivo as well, and further increased the endothelization percentage as compared to PDA coating alone, thus resulting in thinner neointimas. Conclusion These results indicate that PDA coatings with VEGF immobilization would be a promising approach to functionalize Zn surfaces to increase biocompatibility, reduce inflammation, and inhibit neointimal formation after Zn implantation in vivo. Graphical Abstract

Nanomodulator-Mediated Restructuring of Adipose Tissue Immune Microenvironments for Antiobesity Treatment

“…The biocompatibility of VAPN might be attributed to the feature of core material, polydopamine. Consistent with our observation, several studies reported the biocompatibility of polydopamine-based nanoparticles. , The surface coating of nanomaterials with polydopamine has been shown to enhance the biocompatibility of implanted materials …”

“…35,36 The surface coating of nanomaterials with polydopamine has been shown to enhance the biocompatibility of implanted materials. 37 As an all-in-one therapeutic approach, VAPN enhanced beige adipogenesis and restructured the inflammatory microenvironment in adipose tissues by preventing the detrimental interaction between adipocytes and macrophages. To date, few nanoparticulate systems have been developed to treat obesity by modulating the communication between adipocytes and macrophages.…”

Comparison of the Impact of NaIO4-Accelerated, Cu2+/H2O2-Accelerated, and Novel Ion-Accelerated Methods of Poly(l-DOPA) Coating on Collagen-Sealed Vascular Prostheses: Strengths and Weaknesses

“…It should be noted that PDA deposition on vascular implants for their functionalization has already been investigated. According to available literature, popular matrices such as polyurethane, stainless steel, silicon, titanium wafers, expanded poly(tetrafluorethylene) and poly( l -lactide- co -ε-caprolactone) as well as zinc were used to verify these assumptions. − In most of these studies, PDA coating was used to immobilize the vascular endothelial growth factor (VEGF , ), gelatin, or copper . The expected effects of the modification were increased nitric oxide synthesis, increased biocompatibility and hemocompatibility, reduction of neointima formation and macrophage infiltration, rapid endothelialization, and increased neovascularization in surrounding tissues. − However, to our knowledge, no attempts have been made to immobilize PCA on one of the currently most popular vascular grafts, namely, knitted polyester grafts sealed with collagen.…”