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.

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.].

2021, Lu, Bingyang, Han, Xiao, Zhao, Ansha, Luo, Dan, Maitz, Manfred F., Wang, Haohao, Yang, Ping, Huang, Nan

Coronary atherosclerotic lesions exhibit a low-pH chronic inflammatory response. Due to insufficient drug release control, drug-eluting stent intervention can lead to delayed endothelialization, advanced thrombosis, and unprecise treatment. In this study, hyaluronic acid and chitosan were used to prepare pH-responsive self-assembling films. The hydrogen sulfide (H2S) releasing aspirin derivative ACS14 was used as drug in the film. The film regulates the release of the drug adjusted to the microenvironment of the lesion, and the drug balances the vascular function by releasing the regulating gas H2S, which comparably to NO promotes the self-healing capacity of blood vessels. Drug releasing profiles of the films at different pH, and other biological effects on blood vessels were evaluated through blood compatibility, cellular, and implantation experiments. This novel method of self-assembled films which H2S in an amount, which is adjusted to the condition of the lesion provides a new concept for the treatment of cardiovascular diseases.

2022, Lu, Bingyang, Han, Xiao, Zou, Dan, Luo, Xiao, Liu, Li, Wang, Jingyue, Maitz, Manfred F., Yang, Ping, Huang, Nan, Zhao, Ansha

Chronic wounds and the accompanying inflammation are ongoing challenges in clinical treatment. They are usually accompanied by low pH and high oxidative stress environments, limiting cell growth and proliferation. Ordinary medical gauze has limited therapeutic effects on chronic wounds, and there is active research to develop new wound dressings. The chitosan hydrogel could be widely used in biomedical science with great biocompatibility, but the low mechanical properties limit its development. This work uses polyacrylamide to prepare double-network (DN) hydrogels based on bioadhesive catechol-chitosan hydrogels. Cystamine and N, N′-Bis(acryloyl)cystamine, which can be cross-linking agents with disulfide bonds to prepare redox-responsive DN hydrogels and pH-responsive nanoparticles (NPs) prepared by acetalized cyclodextrin (ACD) are used to intelligently release drugs against chronic inflammation microenvironments. The addition of catechol groups and ACD-NPs loaded with the Resolvin E1 (RvE1), promotes cell adhesion and regulates the inflammatory response at the wound site. The preparation of the DN hydrogel in this study can be used to treat and regulate the inflammatory microenvironment of chronic wounds accurately. It provides new ideas for using inflammation resolving factor loaded in DN hydrogel of good biocompatibility with enhanced mechanical properties to intelligent regulate the wound inflammation and promote the wound repaired.

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.

2021, Chen, Jiang, Dai, Sheng, Liu, Luying, Maitz, Manfred F., Liao, Yuzhen, Cui, Jiawei, Zhao, Ansha, Yang, Ping, Huang, Nan, Wang, Yunbing

Titanium dioxide (TiO2) has a long history of application in blood contact materials, but it often suffers from insufficient anticoagulant properties. Recently, we have revealed the photocatalytic effect of TiO2 also induces anticoagulant properties. However, for long-term vascular implant devices such as vascular stents, besides anticoagulation, also anti-inflammatory, anti-hyperplastic properties, and the ability to support endothelial repair, are desired. To meet these requirements, here, we immobilized silver nanoparticles (AgNPs) on the surface of TiO2 nanotubes (TiO2-NTs) to obtain a composite material with enhanced photo-induced anticoagulant property and improvement of the other requested properties. The photo-functionalized TiO2-NTs showed protein-fouling resistance, causing the anticoagulant property and the ability to suppress cell adhesion. The immobilized AgNPs increased the photocatalytic activity of TiO2-NTs to enhances its photo-induced anticoagulant property. The AgNP density was optimized to endow the TiO2-NTs with anti-inflammatory property, a strong inhibitory effect on smooth muscle cells (SMCs), and low toxicity to endothelial cells (ECs). The in vivo test indicated that the photofunctionalized composite material achieved outstanding biocompatibility in vasculature via the synergy of photo-functionalized TiO2-NTs and the multifunctional AgNPs, and therefore has enormous potential in the field of cardiovascular implant devices. Our research could be a useful reference for further designing of multifunctional TiO2 materials with high vascular biocompatibility.

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.