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Jiayin Fu,Qiongjun Zhu,Zhezhe Chen,Jing Zhao,Shaofei Wu,Meng Zhao,Shihui Xu,Dongwu Lai,Guosheng Fu,Wenbin Zhang 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
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.
Li Xuewen,Liu Zihao,Xu Shendan,Ma Xinying,Zhao Zhezhe,Hu Han,Deng Jiayin,Peng Cheng,Wang Yonglan,Ma Shiqing 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) have been shown triggering osteogenic differentiation and mineralization of MSCs, but exosomes administered via bolus injections are rapidly sequestered and cleared. Therefore, we considered the implant as a new organ of patient’s body and expected to find a method to treat implant with BMSC-exos in vivo directly.A fusion peptide (PEP), as a drug delivery system (DDS) which contained a titanium-binding peptide (TBP) possessing the ability to selectively bind to the titanium surface and another peptide CP05 being able to capture exosomes expertly, is constructed to modify the titanium surface.Both in vitro and in vivo experiments prove PEP retains the ability to bind titanium and exosome simultaneously, and the DDS gain the ability to target exosomes to titanium implants surface following enhancing osseointegration post-implantation. Moreover, the DDS constructed by exosomes of diverse origins shows the similar combination rate and efficiency of therapy.This drug delivery system demonstrates the concept that EXO-PEP system can offer an accurate and efficient therapy for treating implants with long-term effect.