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As a metallic orthopedic implant, 316 L stainless steel (316 L SS) is used extensively for its good resistance to corrosion and mechanical properties. However, it takes a long time to achieve osseointegration between 316 L SS and adjacent tissues due to its bio-inert characteristic. Hence, the aim is to improve the bio-adaption of 316 L SS. A good approach is to add elements to materials to improve their osteogenic capabilities by the appropriate release of ions. Hence copper-containing 316 L stainless steel (316L-Cu SS) was investigated in this work, where Cu is an essential trace element that can stimulates osteogenesis. It was found that 316L-Cu SS was bio-safe and did not affect the proliferation of co-cultured osteoblasts in comparison with 316 L SS. It increased cell apoptosis on day 1 but inhibited it on day 3, which cooperates with new bone formation processes. Osteoblasts extend themselves more quickly and in a better manner on the surface of 316L-Cu SS, wheneven more pseudopodia are present. Furthermore, the gene expression of alkaline phosphatase, collagen I and runt-related transcription factor 2 (Runx2) in osteoblasts cultured with 316L-Cu SS was significantly enhanced. Runx2 protein expression increased, and osteogenesis was stimulated by 316L-Cu SS via an Akt cell signaling pathway. In conclusion, 316L-Cu SS stimulates osteogenesis through activation of the Akt cell signaling pathway and the upregulation of Runx2. Thus, 316L-Cu SS is a promising material that may be used in surgical implants to stimulate osteogenesis.

In order to develop a novel kind of antibacterial Cu-containing TiN film with good corrosion resistance, impressive mechanical properties, and low cytotoxicity, three differently designed multilayer films of TiCu/TiCuN multilayer (M1, M2, M3) were deposited on the surface of 316L stainless steel surface using the axial magnetic field-enhanced arc ion plating (AMFE-ARP) method, in which the interlayer of TiCu was first introduced for Cu-containing TiN film in order to improve comprehensive properties, especially the corrosion resistance of the film. The performance of the TiCu/TiCuN multilayer films was compared with that of the two single layers, TiN and TiCuN, which were deposited by the same method and the same total deposition time. The results indicated that the TiCu/TiCuN multilayer film of M2 revealed the best comprehensive corrosion resistance with low electric current values, high pitting potential, and high polarization resistance due to the proper thickness of TiCu interlayers and larger number of TiCu/TiCuN bilayers. In addition, the TiCu/TiCuN multilayer film of M2 also possesses comparable mechanical properties, excellent antibacterial and antibiofilm abilities, as well as good biocompatibility. Consequently, the antibacterial TiCu/TiCuN multilayer films with good corrosion resistance deposited by using the axial magnetic field-enhanced arc ion plating (AMFE-ARP) method are promising for application in biomedical antibacterial film for implants.

Endothelialization is an important process after stenting in coronary artery. Recovery of the injured site timely can reduce the neointima formation and platelet absorbance, leading to a lower risk of in-stent restenosis. Copper is known to be critical in vascular construction. Thus a combination of copper with stent materials is a meaningful attempt. A copper bearing L605-Cu cobalt alloy was prepared and its effect on human umbilical vein endothelial cells (HUVECs) was evaluated in vitro in this study. It was found that HUVECs attached and stretched better on the surface of L605-Cu compared with L605, and the apoptosis of cells was decreased simultaneously. The migration and tube formation of HUVECs were also enhanced by the extract of L605-Cu. Furthermore, L605-Cu increased the mRNA expression of VEGF in HUVECs significantly. However it had no effect on the secretion of NO or mRNA expression of eNOS. The result of blood clotting test indicated that L605-Cu had better blood compatibility. These results above have demonstrated that the L605-Cu alloy is promising to be a new stent material with function of accelerating endothelialization. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 561-569, 2018.

Although being an essential trace element required for human body health, Cu has long been seriously considered toxic when its amount exceeds certain limitation, which significantly limited the wide application of Cu in biomaterials. However, more and more bio-functions and benefits of Cu were found and confirmed, attracting the attention from biomaterials researchers in recent years. People have tried to immobilize Cu into biomaterials by various ways, in order to develop novel bio-functional Cu containing biomaterials with better bio-adaptions, and several different bio-functions of them have been demonstrated. This paper makes a review of the development of novel bio-functional Cu containing biomaterials, and focuses on their unique roles in enhancing bio-adaption of biomedical materials, including antibacterial performance, stimulating angiogenesis, promoting osteogenesis and inhibition of in-stent restenosis, aiming at proposing a prospective development direction for biomedical materials with better bio-adaptions.

This work studied the in vitro angiogenic response of human umbilical vein endothelial cells on the copper-doped titanium nitride (TiCuN) coating, which has been proved to own good antibacterial ability and excellent corrosion resistance as well as wear resistance. It was found that TiCuN coating had no cytotoxic effect and promoted the early cell proliferation, furthermore it significantly promoted the mRNA expressions of eNOS and VEGF, also obviously enhanced the cell migration and tube formation compared with TiN coating, which indicated that TiCuN coating can improve the angiogenesis ability of biomaterials and would gain new opportunities for the applications in orthopedic and cardiovascular fields.

Drug eluting stents (DES) have been extensively applied nowadays and reduce the incidence of in-stent restenosis (ISR) greatly as compared with bare metal stents (BMS). However, the development of DES is hindered by the risk of late stent thrombosis (LST) due to delayed re-endothelialization, while endothelialization is an important process related to ISR and LST after implantation. 316L is a traditional stent material without bioactivity and have a high risk of ISR. Cu is recognized for angiogenesis stimulation in these years. Hence a copper bearing 316L stainless steel (316L-Cu) was prepared and evaluated about its effect on endothelialization in this paper. Compared with traditional 316L, it was proved that 316L-Cu increased the proliferation of co-cultured human umbilical vein endothelial cells (HUVECs) at first day. Moreover, HUVECs stretched better on the surface of 316L-Cu. It also improved the expression of angiogenesis related genes and tube formation ability in vitro. 316L-Cu-BMS, DES and 316L-BMS were implanted in swine to evaluate the re-endothelialization ability in vivo. And 316L-Cu-BMS showed the best effect on endothelialization with good biosafety. Consequently, 316L-Cu is a kind of promising BMS material for coronary field.

Endothelialization is an important process after stenting in coronary artery. Recovery of the injured site timely can reduce the neointima formation and platelet absorbance, leading to a lower risk of in-stent restenosis. Copper is known to be critical in vascular construction. Thus a combination of copper with stent materials is a meaningful attempt. A copper bearing L605-Cu cobalt alloy was prepared and its effect on human umbilical vein endothelial cells (HUVECs) was evaluated in vitro in this study. It was found that HUVECs attached and stretched better on the surface of L605-Cu compared with L605, and the apoptosis of cells was decreased simultaneously. The migration and tube formation of HUVECs were also enhanced by the extract of L605-Cu. Furthermore, L605-Cu increased the mRNA expression of VEGF in HUVECs significantly. However it had no effect on the secretion of NO or mRNA expression of eNOS. The result of blood clotting test indicated that L605-Cu had better blood compatibility. These results above have demonstrated that the L605-Cu alloy is promising to be a new stent material with function of accelerating endothelialization. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 561-569, 2018.