2021, Ma, Qing, Shi, Xiuying, Tan, Xing, Wang, Rui, Xiong, Kaiqin, Maitz, Manfred F., Cui, Yuanyuan, Hu, Zhangmei, Tu, Qiufen, Huang, Nan, Shen, Li, Yang, Zhilu

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.

2020, Xiao, Yu, Wang, Wenxuan, Tian, Xiaohua, Tan, Xing, Yang, Tong, Gao, Peng, Xiong, Kaiqing, Tu, Qiufen, Wang, Miao, Maitz, Manfred F., Huang, Nan, Pan, Guoqing, Yang, Zhilu

In this work, we present a versatile surface engineering strategy by the combination of mussel adhesive peptide mimicking and bioorthogonal click chemistry. The main idea reflected in this work derived from a novel mussel-inspired peptide mimic with a bioclickable azide group (i.e., DOPA4-azide). Similar to the adhesion mechanism of the mussel foot protein (i.e., covalent/noncovalent comediated surface adhesion), the bioinspired and bioclickable peptide mimic DOPA4-azide enables stable binding on a broad range of materials, such as metallic, inorganic, and organic polymer substrates. In addition to the material universality, the azide residues of DOPA4-azide are also capable of a specific conjugation of dibenzylcyclooctyne- (DBCO-) modified bioactive ligands through bioorthogonal click reaction in a second step. To demonstrate the applicability of this strategy for diversified biofunctionalization, we bioorthogonally conjugated several typical bioactive molecules with DBCO functionalization on different substrates to fabricate functional surfaces which fulfil essential requirements of biomedically used implants. For instance, antibiofouling, antibacterial, and antithrombogenic properties could be easily applied to the relevant biomaterial surfaces, by grafting antifouling polymer, antibacterial peptide, and NO-generating catalyst, respectively. Overall, the novel surface bioengineering strategy has shown broad applicability for both the types of substrate materials and the expected biofunctionalities. Conceivably, the “clean” molecular modification of bioorthogonal chemistry and the universality of mussel-inspired surface adhesion may synergically provide a versatile surface bioengineering strategy for a wide range of biomedical materials.

2023, Dou, Zhenglong, Chen, Shuiling, Wang, Jiacheng, Xia, Li, Maitz, Manfred F., Tu, Qiufen, Zhang, Wentai, Yang, Zhilu, Huang, Nan

Control of premature corrosion of magnesium (Mg) alloy bioresorbable stents (BRS) is frequently achieved by the addition of rare earth elements. However, limited long-term experience with these elements causes concerns for clinical application and alternative methods of corrosion control are sought after. Herein, we report a “built-up” composite film consisting of a bottom layer of MgF2 conversion coating, a sandwich layer of a poly (1, 3-trimethylene carbonate) (PTMC) and 3-aminopropyl triethoxysilane (APTES) co-spray coating (PA) and on top a layer of poly (lactic-co-glycolic acid) (PLGA) ultrasonic spray coating to decorate the rare earth element-free Mg–2Zn–1Mn (ZM21) BRS for tailoring both corrosion resistance and biological functions. The developed “built-up” composite film shows synergistic functionalities, allowing the compression and expansion of the coated ZM21 BRS on an angioplasty balloon without cracking or peeling. Of special importance is that the synergistic corrosion control effects of the “built-up” composite film allow for maintaining the mechanical integrity of stents for up to 3 months, where complete biodegradation and no foreign matter residue were observed about half a year after implantation in rabbit iliac arteries. Moreover, the functionalized ZM21 BRS accomplished re-endothelialization within one month.

2021, Xiao, Yu, Wang, Wenxuan, Tian, Xiaohua, Tan, Xing, Yang, Tong, Gao, Peng, Xiong, Kaiqing, Tu, Qiufen, Wang, Miao, Maitz, Manfred F., Huang, Nan, Pan, Guoqing, Yang, Zhilu

[This corrects the article DOI: 10.34133/2020/7236946.].

2022, Zhou, Lei, Zhang, Lu, Li, Peichuang, Maitz, Manfred F., Wang, Kebing, Shang, Tengda, Dai, Sheng, Fu, Yudie, Zhao, Yuancong, Yang, Zhilu, Wang, Jin, Li, Xin

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 (CPU-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.

2020, Yang, Ying, Gao, Peng, Wang, Juan, Tu, Qiufen, Bai, Long, Xiong, Kaiqin, Qiu, Hua, Zhao, Xin, Maitz, Manfred F., Wang, Huaiyu, Li, Xiangyang, Zhao, Qiang, Xiao, Yin, Huang, Nan, Yang, Zhilu

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 × 10a'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 antithrombogenicity, 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. © 2020 American Association for the Advancement of Science. All rights reserved.