Adhesive and Self-Healing Polyurethanes with Tunable Multifunctionality.

Many polyurethanes (PUs) are blood-contacting materials due to their good mechanical properties, fatigue resistance, cytocompatibility, biosafety, and relatively good hemocompatibility. Further functionalization of the PUs using chemical synthetic methods is especially attractive for expanding their applications. Herein, a series of catechol functionalized PU (C-PU-PTMEG) elastomers containing variable molecular weight of polytetramethylene ether glycol (PTMEG) soft segment are reported by stepwise polymerization and further introduction of catechol. Tailoring the molecular weight of PTMEG fragment enables a regulable catechol content, mobility of the chain segment, hydrogen bond and microphase separation of the C-PU-PTMEG elastomers, thus offering tunability of mechanical strength (such as breaking strength from 1.3 MPa to 5.7 MPa), adhesion, self-healing efficiency (from 14.9% to 96.7% within 2 hours), anticoagulant, antioxidation, anti-inflammatory properties and cellular growth behavior. As cardiovascular stent coatings, the C-PU-PTMEGs demonstrate enough flexibility to withstand deformation during the balloon dilation procedure. Of special importance is that the C-PU-PTMEG-coated surfaces show the ability to rapidly scavenge free radicals to maintain normal growth of endothelial cells, inhibit smooth muscle cell proliferation, mediate inflammatory response, and reduce thrombus formation. With the universality of surface adhesion and tunable multifunctionality, these novel C-PU-PTMEG elastomers should find potential usage in artificial heart valves and surface engineering of stents.

The Flow-Induced Degradation and Vascular Cellular Response Study of Magnesium-Based Materials.

Magnesium (Mg)-based materials are considered as potential materials for biodegradable vascular stents, and some Mg-based stents have obtained regulatory approval. However, the development and application of Mg-based stents are still restricted by the rapid degradation rate of Mg and its alloys. In order to screen out the desirable Mg-based materials for stents, the degradation behavior still needs further systematic study, especially the degradation behavior under the action of near-physiological fluid. Currently, the commonly used Mg-based vascular stent materials include pure Mg, AZ31, and WE43. In this study, we systematically evaluated their corrosion behaviors in a dynamic environment and studied the effect of their degradation products on the behavior of vascular cells. The results revealed that the corrosion rate of different Mg-based materials was related to the composition of the elements. The dynamic environment accelerated the corrosion of Mg-based materials. All the same, AZ31 still shows good corrosion resistance. The effect of corrosive products on vascular cells was beneficial to re-endothelialization and inhibition of smooth muscle cell proliferation at the implantation site of vascular stent materials.

Application of a Reactive Oxygen Species-Responsive Drug-Eluting Coating for Surface Modification of Vascular Stents.

Stent implantation is the primary method used to treat coronary heart disease. However, it is associated with complications such as restenosis and late thrombosis. Despite surface modification being an effective way to improve the biocompatibility of stents, the current research studies are not focused on changes in the vascular microenvironment at the implantation site. In the present study, an adaptive drug-loaded coating was constructed on the surface of vascular stent materials that can respond to oxidative stress at the site of vascular lesions. Two functional molecules, epigallocatechin gallate (EGCG) and cysteine hydrochloride, were employed to fabricate a coating on the surface of 316L stainless steel. In addition, the coating was used as a drug carrier to load pitavastatin calcium. EGCG has antioxidant activity, and pitavastatin calcium can inhibit smooth muscle cell proliferation. Therefore, EGCG and pitavastatin calcium provided a synergistic anti-inflammatory effect. Moreover, the coating was cross-linked using disulfide bonds, which accelerated the release of the drug in response to reactive oxygen species. A positive correlation was observed between the rate of drug release and the degree of oxidative stress. Collectively, this drug-loaded oxidative stress-responsive coating has been demonstrated to significantly inhibit inflammation, accelerate endothelialization, and reduce the risk of restenosis of vascular stents in vivo.

Cu∥-loaded polydopamine coatings with in situ nitric oxide generation function for improved hemocompatibility.

NO is the earliest discovered gas signal molecule which is produced by normal healthy endothelial cells, and it has many functions, such as maintaining cardiovascular homeostasis, regulating vasodilation, inhibiting intimal hyperplasia and preventing atherosclerosis in the blood system. Insufficient NO release is often observed in the pathological environment, for instance atherosclerosis. It was discovered that NO could be released from the human endogenous NO donor by many compounds, and these methods can be used for the treatment of certain diseases in the blood system. In this work, a series of copper-loaded polydopamine (PDA) coatings were produced through self-polymerization time for 24, 48 and 72 h. The chemical composition and structure, coating thickness and hydrophilicity of the different copper-loaded PDA coatings surfaces were characterized by phenol hydroxyl quantitative, X-ray photoelectron spectroscopy, ellipsometry atomic force microscopy and water contact angles. The results indicate that the thickness and the surface phenolic hydroxyl density of the PDA coatings increased with the polymerization time.This copper-loaded coating has glutathione peroxidase-like activity, and it has the capability of catalyzing NO releasing from GSNO. The surface of the coating showed desirable hemocompatibility, the adhesion and activation of platelets were inhibited on the copper-loaded coatings. At the same time, the formation of the thrombosis was also suppressed. These copper-loaded PDA coatings could provide a promising platform for the development of blood contact materials.

An Albumin Biopassive Polyallylamine Film with Improved Blood Compatibility for Metal Devices.

Nowadays, a variety of materials are employed to make numerous medical devices, including metals, polymers, ceramics, and others. Blood-contact devices are one of the major classes of these medical devices, and they have been widely applied in clinical settings. Blood-contact devices usually need to have good mechanical properties to maintain clinical performance. Metal materials are one desirable candidate to fabricate blood-contact devices due to their excellent mechanical properties and machinability, although the blood compatibility of existing blood-contact devices is better than other medical devices, such as artificial joints and artificial crystals. However, blood coagulation still occurs when these devices are used in clinical settings. Therefore, it is necessary to develop a new generation of blood-contact devices with fewer complications, and the key factor is to develop novel biomaterials with good blood compatibility. In this work, one albumin biopassive polyallylamine film was successfully established onto the 316L stainless steel (SS) surface. The polyallylamine film was prepared by plasma polymerization in the vacuum chamber, and then polyallylamine film was annealed at 150 °C for 1 h. The chemical compositions of the plasma polymerized polyallylamine film (PPAa) and the annealed polyallylamine film (HT-PPAa) were characterized by Fourier transform infrared spectrum (FTIR). Then, the wettability, surface topography, and thickness of the PPAa and HT-PPAa were also evaluated. HT-PPAa showed increased stability when compared with PPAa film. The major amino groups remained on the surface of HT-PPAa after annealing, indicating that this could be a good platform for numerous molecules' immobilization. Subsequently, the bovine serum albumin (BSA) was immobilized onto the HT-PPAa surface. The successful introduction of the BSA was confirmed by the FTIR and XPS detections. The blood compatibility of these modified films was evaluated by platelets adhesion and activation assays. The number of the platelets that adhered on BSA-modified HT-PPAa film was significantly decreased, and the activation degree of the adhered platelets was also decreased. These data revealed that the blood compatibility of the polyallylamine film was improved after BSA immobilized. This work provides a facile and effective approach to develop novel surface treatment for new-generation blood-contact devices with improved hemocompatibility.

Catechol/polyethyleneimine conversion coating with enhanced corrosion protection of magnesium alloys: potential applications for vascular implants.

Magnesium (Mg) alloys are promising biodegradable materials but challenges remain due to their rapid degradation, especially in the potential use of Mg alloys as vascular stents. Surface modification techniques are the most straightforward way to address both the desired biocompatibility and inhibit the corrosion of Mg alloys. In this work, inspired by the functional moieties (catechols) of mussel adhesive proteins, a mimetic approach to construct organic protective conversion coatings on magnesium-zinc-manganese (MgZnMn) alloys is investigated. Based on the cross-linking of CA (catechol) and PEI (polyethyleneimine), a CA/PEI conversion coating is developed on a MgZnMn alloy. The CA/PEI conversion coating showed enhanced corrosion resistance due to the strong binding and aggregation of units. Moreover, such coatings could also provide enough primary amine groups, catechols and quinones, which can be used to immobilize further molecules. Heparin was further grafted onto the CA/PEI, endowing the conversion coating with the desired functionality. Vascular cell behavior on such a coating is also studied. The improved hemocompatibility, favorable anti-inflammatory ability, suppressed smooth muscle cell proliferation and enhanced endothelialization indicate the potential of such organic conversion coatings on MgZnMn alloys as vascular implants.