Mussel-Inspired and Bioclickable Peptide Engineered Surface to Combat Thrombosis and Infection.

Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices, leading to significant mortality in clinic. To address this issue, here, we report a biomimetic surface engineering strategy by the integration of mussel-inspired adhesive peptide, with bio-orthogonal click chemistry, to tailor the surface functionalities of tubing and catheters. Inspired by mussel adhesive foot protein, a bioclickable peptide mimic (DOPA)4-azide-based structure is designed and grafted on an aminated tubing robustly based on catechol-amine chemistry. Then, the dibenzylcyclooctyne (DBCO) modified nitric oxide generating species of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated copper ions and the DBCO-modified antimicrobial peptide (DBCO-AMP) are clicked onto the grafted surfaces via bio-orthogonal reaction. The combination of the robustly grafted AMP and Cu-DOTA endows the modified tubing with durable antimicrobial properties and ability in long-term catalytically generating NO from endogenous s-nitrosothiols to resist adhesion/activation of platelets, thus preventing the formation of thrombosis. Overall, this biomimetic surface engineering technology provides a promising solution for multicomponent surface functionalization and the surface bioengineering of biomedical devices with enhanced clinical performance.

Durable endothelium-mimicking coating for surface bioengineering cardiovascular stents.

Mimicking the nitric oxide (NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis (ISR) effectively. However, the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx component. Herein, we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species (e.g., Cu-DOTA coordination complex) and glycocalyx-like component (e.g., heparin) to create a durable endothelium-mimicking surface. The stent surface was firstly coated with polydopamine (pDA), followed by a surface chemical cross-link with polyamine (pAM) to form a durable pAMDA coating. Using a stepwise grafting strategy, Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide chemistry. Owing to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules, this proposed strategy could provide 62.4% bioactivity retention ratio of heparin, meanwhile persistently generate NO at physiological level from 5.9 ± 0.3 to 4.8 ± 0.4 × 10-10 mol cm-2 min-1 in 1 month. As a result, the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis, inflammation, and intimal hyperplasia, enhanced re-endothelialization, and hence efficiently reduced ISR.

Endothelium-Mimicking Surface Combats Thrombosis and Biofouling via Synergistic Long- and Short-Distance Defense Strategy.

Thrombosis and infections are the main causes of implant failures (e.g., extracorporeal circuits and indwelling medical devices), which induce significant morbidity and mortality. In this work, an endothelium-mimicking surface is engineered, which combines the nitric oxide (NO)-generating property and anti-fouling function of a healthy endothelium. The released gas signal molecules NO and the glycocalyx matrix macromolecules hyaluronic acid (HA) jointly combine long- and short-distance defense actions against thrombogenicity and biofouling. The biomimetic surface is efficiently fabricated by cografting a NO-generating species (i.e., Tri-tert-butyl 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetate-chelated Cu2+ , DTris@Cu) and the macromolecular HA on an aminated tube surface through one-pot amide condensation chemistry. The active attack (i.e., NO release) and zone defense (i.e., HA tethering) system endow the tubing surface with significant inhibition of platelets, fibrinogen, and bacteria adhesion, finally leading to long-term anti-thrombogenic and anti-fouling properties over 1 month. It is envisioned that this endothelium-mimicking surface engineering strategy will provide a promising solution to address the clinical issues of long-term blood-contacting devices associated with thrombosis and infection.

Phenolic-amine chemistry mediated synergistic modification with polyphenols and thrombin inhibitor for combating the thrombosis and inflammation of cardiovascular stents.

Antithrombogenicity, anti-inflammation, and rapid re-endothelialization are central requirements for the long-term success of cardiovascular stents. In this work, a plant-inspired phenolic-amine chemistry strategy was developed to combine the biological functions of a plant polyphenol, tannic acid (TA), and the thrombin inhibitor bivalirudin (BVLD) for tailoring the desired multiple surface functionalities of cardiovascular stents. To realize the synergistic modification of TA and BVLD on a stent surface, an amine-bearing coating of plasma polymerized allylamine was firstly prepared on the stent surface, followed by the sequential conjugation of TA and BVLD in alkaline solution based on phenolic-amine chemistry (i.e., Michael addition reaction). TA and BVLD were successfully immobilized onto the stent surface with considerable amounts of 330 ± 12 and 930 ± 80 ng/cm2, respectively. The abundant phenolic hydroxyl groups of TA imparted the stent with ability to suppress inflammation. Meanwhile, BVLD provided an antithrombogenic and endothelial-friendly microenvironment. As a result, the combined functions of the TA and BVLD facilitate the rapid stent re-endothelialization for reduced intimal hyperplasia in vivo, and may be a promising strategy to address the clinical complications associated with restenosis and late stent thrombosis.

Nitric oxide-generating compound and bio-clickable peptide mimic for synergistically tailoring surface anti-thrombogenic and anti-microbial dual-functions.

Application of extracorporeal circuits and indwelling medical devices has saved many lives. However, it is accompanied with two major complications: thrombosis and infection. To address this issue, we apply therapeutic nitric oxide gas (NO) and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual functions. Such functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated copper ions (Cu-DOTA) and dibenzylcyclooctyne- (DBCO-) modified antimicrobial peptide based on carbodiimide and click chemistry respectively. The integration of peptide and Cu-DOTA grants the modified surface the ability to not only efficiently inhibit bacterial growth, but also catalytically generate NO from endogenous s-nitrosothiols (RSNO) to reduce adhesion and activation of platelets, preventing the formation of thrombus. We envision that the stepwise synergistic modification strategy by using anticoagulant NO and antibacterial peptide would facilitate the surface multifunctional engineering of extracorporeal circuits and indwelling medical devices, with reduced clinical complications associated with thrombosis and infection.

Poly-dopamine, poly-levodopa, and poly-norepinephrine coatings: Comparison of physico-chemical and biological properties with focus on the application for blood-contacting devices.

Thanks to its simplicity, versatility, and secondary reactivity, dopamine self-polymerized coatings (pDA) have been widely used in surface modification of biomaterials, but the limitation in secondary molecular grafting and the high roughness restrain their application in some special scenarios. Therefore, some other catecholamine coatings analog to pDA have attracted more and more attention, including the smoother poly-norepinephrine coating (pNE), and the poly-levodopa coating (pLD) containing additional carboxyl groups. However, the lack of a systematic comparison of the properties, especially the biological properties of the above three catecholamine coatings, makes it difficult to give a guiding opinion on the application scenarios of different coatings. Herein, we systematically studied the physical, chemical, and biological properties of the three catecholamine coatings, and explored the feasibility of their application for the modification of biomaterials, especially cardiovascular materials. Among them, the pDA coating was the roughest, with the largest amount of amino and phenolic hydroxyl groups for molecule grafting, and induced the strongest platelet adhesion and activation. The pLD coating was the thinnest and most hydrophilic but triggered the strongest inflammatory response. The pNE coating was the smoothest, with the best hemocompatibility and histocompatibility, and with the strongest cell selectivity of promoting the proliferation of endothelial cells while inhibiting the proliferation of smooth muscle cells. To sum up, the pNE coating may be a better choice for the surface modification of cardiovascular materials, especially those for vascular stents and grafts, but it is still not widely recognized.

Mimicking the Nitric Oxide-Releasing and Glycocalyx Functions of Endothelium on Vascular Stent Surfaces.

Endothelium can secrete vasoactive mediators and produce specific extracellular matrix, which contribute jointly to the thromboresistance and regulation of vascular cell behaviors. From a bionic point of view, introducing endothelium-like functions onto cardiovascular stents represents the most effective means to improve hemocompatibility and reduce late stent restenosis. However, current surface strategies for vascular stents still have limitations, like the lack of multifunctionality, especially the monotony in endothelial-mimic functions. Herein, a layer-by-layer grafting strategy to create endothelium-like dual-functional surface on cardiovascular scaffolds is reported. Typically, a nitric oxide (NO, vasoactive mediator)-generating compound and an endothelial polysaccharide matrix molecule hyaluronan (HA) are sequentially immobilized on allylamine-plasma-deposited stents through aqueous amidation. In this case, the stents could be well-engineered with dual endothelial functions capable of remote and close-range regulation of the vascular microenvironment. The synergy of NO and endothelial glycocalyx molecules leads to efficient antithrombosis, smooth muscle cell (SMC) inhibition, and perfect endothelial cell (EC)-compatibility of the stents in vitro. Moreover, the dual-functional stents show efficient antithrombogenesis ex vivo, rapid endothelialization, and long-term prevention of restenosis in vivo. Therefore, this study will provide new solutions for not only multicomponent surface functionalization but also the bioengineering of endothelium-mimic vascular scaffolds with improved clinical outcomes.

Endothelium-Mimicking Multifunctional Coating Modified Cardiovascular Stents via a Stepwise Metal-Catechol-(Amine) Surface Engineering Strategy.

Stenting is currently the major therapeutic treatment for cardiovascular diseases. However, the nonbiogenic metal stents are inclined to trigger a cascade of cellular and molecular events including inflammatory response, thrombogenic reactions, smooth muscle cell hyperproliferation accompanied by the delayed arterial healing, and poor reendothelialization, thus leading to restenosis along with late stent thrombosis. To address prevalence critical problems, we present an endothelium-mimicking coating capable of rapid regeneration of a competently functioning new endothelial layer on stents through a stepwise metal (copper)-catechol-(amine) (MCA) surface chemistry strategy, leading to combinatorial endothelium-like functions with glutathione peroxidase-like catalytic activity and surface heparinization. Apart from the stable nitric oxide (NO) generating rate at the physiological level (2.2 × 10-10 mol/cm2/min lasting for 60 days), this proposed strategy could also generate abundant amine groups for allowing a high heparin conjugation efficacy up to ∼1 µg/cm2, which is considerably higher than most of the conventional heparinized surfaces. The resultant coating could create an ideal microenvironment for bringing in enhanced anti-thrombogenicity, anti-inflammation, anti-proliferation of smooth muscle cells, re-endothelialization by regulating relevant gene expressions, hence preventing restenosis in vivo. We envision that the stepwise MCA coating strategy would facilitate the surface endothelium-mimicking engineering of vascular stents and be therefore helpful in the clinic to reduce complications associated with stenosis.

Metal-catechol-(amine) networks for surface synergistic catalytic modification: Therapeutic gas generation and biomolecule grafting.

Regarding the high requirement of cardiac and vascular implants in tissue engineering, a novel concept of surface chemistry strategy featuring multiple functions is proposed in this study, which provides glutathione peroxidase (GPx)-like catalytic activity and allows secondary reactions for grafting functional biomolecules. The suggested strategy is the fabrication of a metal-catechol-(amine) network (MCAN) containing copper ions with GPx-like activity, amine-bearing hexamethylenediamine (HD) and wet adhesive catechol dopamine (DA). With a simple one-step molecular/ion co-assembly, the developed copper-DA-HD (CuII-DA/HD) network can be used to catalyze the generation of therapeutic nitric oxide (NO) gas in a durable and dose-controllable manner. The primary amine groups in the CuII-DA/HD network facilitate the secondary immobilization of bivalirudin (BVLD) to further provide an antithrombotic activity as supplement to the functions of NO. The CuII-DA/HD + BVLD coating functionalized on cardiovascular stents successfully improved thromboresistance, anti-restenosis, and promotes re-endothelialization in vivo. With regard to the ease of operation and low cost, the synergetic modification using MCAN strategy is of great potential for developing multifunctional blood-contacting materials/devices.

From surface to bulk modification: Plasma polymerization of amine-bearing coating by synergic strategy of biomolecule grafting and nitric oxide loading.

Integration of two or more biomolecules with synergetic and complementary effects on a material surface can help to obtain multi-functions for various biomedical applications. However, the amounts of biomolecules integrated and their physiological functions are compromised due to the limited surface anchoring sites. Herein, we propose a novel concept of film engineering strategy "from surface to bulk synergetic modification". This new concept is realized by employing the surface amine groups of plasma polymerized allylamine (PPAm) film for grafting a molecule e.g., thrombin inhibitor, bivalirudin (BVLD), meanwhile its bulk amine groups is used as a universal depot for storing and releasing therapeutic nitric oxide (NO) gas as supplement to the functions of BVLD. It is demonstrated that such a "from surface to bulk synergetic modification" film engineering can impart the modified-substrates with anti-platelet and anti-coagulant dual functions, giving rise to a highly endothelium-mimetic thromboresistant property. We believe that our research provides a very promising strategy to deliver multifunctional surface versatilely that require NO release in combination with other properties, which will find broad biomedical applications in blood-contacting devices, and et al. Moreover, it also provides a brand-new film engineering strategy for tailoring surface multi-functionalities of a wide range of materials.

A facile dopamine-mediated metal-catecholamine coating for therapeutic nitric oxide gas interface-catalytic engineering of vascular devices.

Developing a facile and versatile strategy to endow blood-contacting devices with surface in situ nitric oxide (NO) generation properties by catalytically decomposing endogenously existing S-nitrosothiols (RSNO) from blood is of immense scientific and engineering interest. However, most available strategies involve drawbacks of low efficiency, complex processes, and toxic chemicals. In this work, we report a facile method to deposit a NO-generating coating on a 316L stainless steel (SS) substrate through dopamine-mediated one-step assembly of CuII-dopamine (CuII-DA) coordination complexes. The chelation of CuII in the CuII-DA network endowed the coating with high in situ NO catalytic capacity by decomposing RSNO endogenously existing in blood. Of special importance is that this dopamine-mediated method possesses the merits of a simple preparation process, friendliness to the environment, high controllability of the CuII-DA surface chemistry, highly effective surface coating formation, and long-term and durable catalytic activity of NO. The continuous release of NO from the CuII-DA-coated 316L SS impressively improved its antithrombogenicity and selectively enhanced endothelial cell (EC) growth while inhibiting smooth muscle cell (SMC) proliferation.

Photolithography-Mediated Area-Selective Immobilization of Biomolecules on Polydopamine Coating.

Functional microdomains consisting of multiple molecules have widespread applications. However, most of available methods reported so far have a common limitation for widespread practical use. Herein, we reported a facile method based on material-independent polydopamine surface chemistry to realize the area-selective immobilization of dual amine-/thiol-terminal bioactive molecules assisted by photolithography. We transferred the photoresist pattern to the polydopamine coating surface, and specific molecules were respectively covalently immobilized in the microdomain. The results demonstrated that molecular anchoring is area-selective and quantitatively controllable. Thus, this versatile method provides a new insight into the creation of regionally chemical multicomponent surfaces and could build a potential platform for promising application in sensors, molecular biology, and genetic diagnosis.

Assembly of Metal-Phenolic/Catecholamine Networks for Synergistically Anti-Inflammatory, Antimicrobial, and Anticoagulant Coatings.

The development of a facile and versatile strategy to endow surfaces with synergistically anti-inflammatory, antimicrobial, and anticoagulant functions is of particular significance for blood-contacting biomaterials and medical devices. In this work, we report a simple and environmentally friendly "one-pot" method inspired by byssal cuticle chemistry, namely, [Fe(dopa)3] coordination chemistry for assembly of copper ions (Cu2+) and plant polyphenol (tannic acid)/catecholamine (dopamine or norepinephrine) to form metal-phenolic/catecholamine network-based coatings. This one-pot method enabled us to easily develop a multifunctional surface based on the combination of the characteristic functions of metal ions and plant polyphenol or catecholamine. The residual phenolic hydroxyl groups on the coatings imparted the modified surface with excellent antioxidant and anti-inflammatory functions. The robust chelation of copper ions to the metal-phenolic/catecholamine networks provided not only durable antibacterial property but also glutathione peroxidase like catalytic capability to continuously and controllably produce antithrombotic nitric oxide by catalyzing endogenous S-nitrothiol. The biological functions of such coatings could be well regulated by adjusting the ratios of the feed concentration of Cu2+ ions to plant polyphenol or catecholamine. We envision that our simple, multifunctional, and bioinspired coating strategy can hold great application promise for bioengineering blood-contacting devices.

Mussel-inspired catalytic selenocystamine-dopamine coatings for long-term generation of therapeutic gas on cardiovascular stents.

The development of a nitric oxide (NO)-generating surface with long-term, stable and controllable NO release improves the therapeutic efficacy of cardiovascular stents. In this work, we developed a "one-pot" method inspired by mussel adhesive proteins for copolymerization of selenocystamine (SeCA) and dopamine (Dopa) to form a NO-generating coating on a 316 L stainless steel (SS) stent. This "one-pot" method is environmentally friendly and easy to popularize, with many advantages including simple manufacturing procedure, high stability and no involvement of organic solvents. Such SeCA/Dopa coatings also enabled us to develop a catalytic surface for local NO-generation by reaction of endogenously existing S-nitrothiol species from fresh blood. We found that the developed SeCA/Dopa coatings could release NO in a controllable and stable manner for more than 60 days. Additionally, the released NO significantly inhibited smooth muscle cell (SMC) proliferation and migration, as well as platelet activation and aggregation through the up-regulation of cyclic guanosine monophosphate synthesis. Moreover, such NO generation enhanced the adhesion, proliferation and migration of endothelial cells (ECs), and achieved rapid in vivo re-endothelialization, effectively reducing in-stent restenosis and neointimal hyperplasia. We envision that the SeCA/Dopa-coated 316 L SS stent could be a promising platform for treatment of cardiovascular diseases.

Multifunctional coating based on EPC-specific peptide and phospholipid polymers for potential applications in cardiovascular implants fate.

Surface biofunctional modification of cardiovascular implants via the conjugation of biomolecules to prevent thrombosis and restenosis formation and to accelerate endothelialization has attracted considerable research interest. In this study, we aimed to develop a multifunctional surface that could exhibit good hemocompatibility and function well in inducing desirable vascular cell-material interactions. The multifunctional coating (PCDLOPTPT@Ti), containing phosphorylcholine groups and endothelial progenitor cell (EPC)-specific peptides (PT), was prepared on titanium (Ti) surfaces via chemical conjugation. The results of platelet adhesion, activation, fibrinogen denaturation, and whole blood dynamic adhesion testing indicated that the PCDLOPTPT@Ti coating presented a better hemocompatibility when compared with bare Ti and other control samples. In vitro EPC and smooth muscle cell (SMC) cultures showed that the PCDLOPTPT@Ti coating significantly promoted the adhesion and proliferation of EPCs and inhibited the attachment and proliferation of SMCs. In vivo animal tests further confirmed that the PCDLOPTPT@Ti coating effectively inhibited thrombus formation and intimal hyperplasia while supporting endothelium regeneration. These results effectively suggest that the PCDLOPTPT@Ti coating may be promising as a coating on cardiovascular implants.

Nitric oxide producing coating mimicking endothelium function for multifunctional vascular stents.

The continuous release of nitric oxide (NO) by the native endothelium of blood vessels plays a substantial role in the cardiovascular physiology, as it influences important pathways of cardiovascular homeostasis, inhibits vascular smooth muscle cell (VSMC) proliferation, inhibits platelet activation and aggregation, and prevents atherosclerosis. In this study, a NO-catalytic bioactive coating that mimics this endothelium functionality was presented as a hemocompatible coating with potential to improve the biocompatibility of vascular stents. The NO-catalytic bioactive coating was obtained by covalent conjugation of 3,3-diselenodipropionic acid (SeDPA) with glutathione peroxidase (GPx)-like catalytic activity to generate NO from S-nitrosothiols (RSNOs) via specific catalytic reaction. The SeDPA was immobilized to an amine bearing plasma polymerized allylamine (PPAam) surface (SeDPA-PPAam). It showed long-term and continuous ability to catalytically decompose endogenous RSNO and generate NO. The generated NO remarkably increased the cGMP synthesis both in platelets and human umbilical artery smooth muscle cells (HUASMCs). The surface exhibited a remarkable suppression of collagen-induced platelet activation and aggregation. It suppressed the adhesion, proliferation and migration of HUASMCs. Additionally, it was found that the NO catalytic surface significantly enhanced human umbilical vein endothelial cell (HUVEC) adhesion, proliferation and migration. The in vivo results indicated that the NO catalytic surface created a favorable microenvironment of competitive growth of HUVECs over HUASMCs for promoting re-endothelialization and reducing restenosis of stents in vivo.

A biocompatible and functional adhesive amine-rich coating based on dopamine polymerization.

Amine groups physiologically play an important role in regulating the growth behavior of cells and they have technological advantages for the conjugation of biomolecules. In this work, we present a method to deposit a copolymerized coating of dopamine and hexamethylendiamine (HD) (PDAM/HD) rich in amine groups onto a target substrate. This method only consists of a simple dip-coating step of the substrate in an aqueous solution consisting of dopamine and HD. Using the technique of PDAM/HD coating, a high density of amine groups of about 30 nmol cm-2 was obtained on the target substrate surface. The PDAM/HD coating showed a high cross-linking degree that is robust enough to resist hydrolysis and swelling. As a vascular stent coating, the PDAM/HD presented good adhesion strength to the substrate and resistance to the deformation behavior of compression and expansion of a stent. Meanwhile, the PDAM/HD coating exhibited good biocompatibility and attenuated the tissue response compared with 316L stainless steel (SS). The primary amine groups of the PDAM/HD coating could be used to effectively immobilize biomolecules containing carboxylic groups such as heparin. These data suggested the promising potential of this PDAM/HD coating for application in the surface modification of biomedical devices.

Proliferation and functionality of human umbilical vein endothelial cells on angiopoietin-1 immobilized 316L stainless steel.

Angiopoietin-1 (Ang-1), a vascular-specific growth factor secreted from periendothelial cells, has drawn increasing attention in clinical applications because it can promote the reconstruction of blood vessels and has an anti-inflammatory effect compared with vascular endothelial growth factor (VEGF). In this study, Ang-1 was firstly covalently conjugated onto polydopamine (PDA) coated 316L stainless steel (SS), aiming at developing an Ang-l modified surface for endothelialization. The results of Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and water contact angle (WCA) measurements confirmed the successful immobilization of Ang-1. Quartz crystal microbalance with dissipation (QCM-D) studies demonstrated that ∼154 ng cm-2 of Ang-1 were bonded onto the PDA surface. To confirm its functionality, the effects of the Ang-1-modified coating on the growth behavior of human umbilical vein endothelial cells (HUVECs) were studied. As a result, the Ang-1 functionalized surface significantly enhanced endothelial cell adhesion, proliferation and migration. It was also found the Ang-1 functionalized coating could promote the release of nitric oxide (NO), secretion of prostacyclin-2 (PGI2) and inhibit the apoptosis of HUVECs. These data effectively suggested angiopoietin-1 could potentially be applied not only in neovascularization such as ischemic reperfusion and vascularization of tissue engineering scaffolds, but also in surface modification of cardiovascular implant materials for re-endothelialization.

Multifunctional Plasma-Polymerized Film: Toward Better Anticorrosion Property, Enhanced Cellular Growth Ability, and Attenuated Inflammatory and Histological Responses.

Over the past few decades, plasma surface modification technique has been widely used to selectively improve surface properties and biocompatibility of materials. In this paper, at first a simple and effective method for the deposition of plasma-polymerized allylamine films onto 316L stainless steel (SS) from an allylamine/nitrogen gas mixture was developed. These amine-rich films were characterized by grazing incidence attenuated total reflection Fourier transform infrared spectroscopy (GATR-FTIR) and X-ray photoelectron spectroscopy (XPS), and the anticorrosion properties were demonstrated by electrochemical analysis. Micro-BCA and quartz crystal microbalance with dissipation (QCM-D) results showed that the higher density of amine groups of the allylamine-nitrogen plasma-polymerized film contributes to more serum protein adsorption which may enhance the adhesion and growth of cells on biomaterials. The in vitro and in vivo anti-inflammatory evaluation was performed and it has been confirmed that these nitrogen-rich surfaces could inhibit the activation of macrophages by down-regulation of the pro-inflammatory cytokines TNF-α and IL-6, and exhibit acceptable tissue-compatibility. It was found that with the help of nitrogen, plasma-polymerized allylamine films presented superior biological properties and provided a high potential application in surface modification of biomedical substrate with desirable clinical performance.