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- ItemDurable endothelium-mimicking coating for surface bioengineering cardiovascular stents([Bejing] : KeAi Publishing, 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, ZhiluMimicking 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.
- ItemIntelligent H2S release coating for regulating vascular remodeling(Bejing : KeAi Publishing, 2021) Lu, Bingyang; Han, Xiao; Zhao, Ansha; Luo, Dan; Maitz, Manfred F.; Wang, Haohao; Yang, Ping; Huang, NanCoronary 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.
- ItemPhoto-functionalized TiO2 nanotubes decorated with multifunctional Ag nanoparticles for enhanced vascular biocompatibility(Bejing : KeAi Publishing, 2021) Chen, Jiang; Dai, Sheng; Liu, Luying; Maitz, Manfred F.; Liao, Yuzhen; Cui, Jiawei; Zhao, Ansha; Yang, Ping; Huang, Nan; Wang, YunbingTitanium 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.
- ItemA “built-up” composite film with synergistic functionalities on Mg–2Zn–1Mn bioresorbable stents improves corrosion control effects and biocompatibility([Bejing] : KeAi Publishing, 2023) Dou, Zhenglong; Chen, Shuiling; Wang, Jiacheng; Xia, Li; Maitz, Manfred F.; Tu, Qiufen; Zhang, Wentai; Yang, Zhilu; Huang, NanControl 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.
- ItemFormer Training Relieves the Later Development of Behavioral Inflexibility in an Animal Model Overexpressing the Dopamine Transporter(Totowa, NJ : Humana Press, 2022) Edemann-Callesen, Henriette; Glienke, Maximilian; Akinola, Esther Olubukola; Lieser, Maike Kristin; Habelt, Bettina; Hadar, Ravit; Bernhardt, Nadine; Winter, ChristineA range of dopamine-dominating neuropsychiatric disorders present with cognitive deficits. In accordance, the dopamine transporter overexpressing rat model (DAT-tg rat) displays cognitive deficits by means of behavioral inflexibility and learning disabilities. It remains to be investigated when cognitive deficits emerge, due to the inherent DA irregularities, during the life course of the DAT-tg rat and what may relieve symptoms. The Morris water maze (MWM) was used to assess cognitive abilities in three cohorts of DAT-tg rats. In the first cohort, the development of cognitive deficits was assessed by repeatedly testing animals in the MWM at postnatal day (PND) 35, 60, and 90. In the second and third cohort, pharmacological interventions and transcranial direct current stimulation (tDCS) were tested in adult animals to understand what drives, and thus relieves, the deficits. Minor differences were observed between DAT-tg rats and control rats at PND 35 and 60, whereas cognitive deficits fully emerged at PND 90. A high dosage of methylphenidate diminished both behavioral inflexibility and improved learning abilities in adult rats. Interestingly, rats subjected early in life to the MWM also displayed improved behavioral flexibility as compared to rats naïve to the paradigm. Cognitive deficits gradually develop over time and fully emerge in adulthood. Pharmacological modulation of the ubiquitous DAT overexpression overall improves deficits in adult rats, whereas early training decreases later development of behavioral inflexibility. Thus, former training may constitute a preventive avenue that alters some aspects of cognitive deficits resulting from inherent DA abnormalities.
- ItemThermo-responsive cell culture carrier: Effects on macrophage functionality and detachment efficiency(London : Sage, 2017) Rennert, Knut; Nitschke, Mirko; Wallert, Maria; Keune, Natalie; Raasch, Martin; Lorkowski, Stefan; Mosig, Alexander S.Harvesting cultivated macrophages for tissue engineering purposes by enzymatic digestion of cell adhesion molecules can potentially result in unintended activation, altered function, or behavior of these cells. Thermo-responsive polymer is a promising tool that allows for gentle macrophage detachment without artificial activation prior to subculture within engineered tissue constructs. We therefore characterized different species of thermo-responsive polymers for their suitability as cell substrate and to mediate gentle macrophage detachment by temperature shift. Primary human monocyte- and THP-1-derived macrophages were cultured on thermo-responsive polymers and characterized for phagocytosis and cytokine secretion in response to lipopolysaccharide stimulation. We found that both cell types differentially respond in dependence of culture and stimulation on thermo-responsive polymers. In contrast to THP-1 macrophages, primary monocyte–derived macrophages showed no signs of impaired viability, artificial activation, or altered functionality due to culture on thermo-responsive polymers compared to conventional cell culture. Our study demonstrates that along with commercially available UpCell carriers, two other thermo-responsive polymers based on poly(vinyl methyl ether) blends are attractive candidates for differentiation and gentle detachment of primary monocyte–derived macrophages. In summary, we observed similar functionality and viability of primary monocyte–derived macrophages cultured on thermo-responsive polymers compared to standard cell culture surfaces. While this first generation of custom-made thermo-responsive polymers does not yet outperform standard culture approaches, our results are very promising and provide the basis for exploiting the unique advantages offered by custom-made thermo-responsive polymers to further improve macrophage culture and recovery in the future, including the covalent binding of signaling molecules and the reduction of centrifugation and washing steps. Optimizing these and other benefits of thermo-responsive polymers could greatly improve the culture of macrophages for tissue engineering applications.
- ItemIn vitro pre-vascularisation of tissue-engineered constructs A co-culture perspective(London : BioMed Central, 2014) Baldwin, J.; Antille, M.; Bonda, U.; De-Juan-Pardo, E.M.; Khosrotehrani, K.; Ivanovski, S.; Petcu, E.B.; Hutmacher, D.W.In vitro pre-vascularization is one of the main vascularization strategies in the tissue engineering field. Culturing cells within a tissue-engineered construct (TEC) prior to implantation provides researchers with a greater degree of control over the fate of the cells. However, balancing the diverse range of different cell culture parameters in vitro is seldom easy and in most cases, especially in highly vascularized tissues, more than one cell type will reside within the cell culture system. Culturing multiple cell types in the same construct presents its own unique challenges and pitfalls. The following review examines endothelial-driven vascularization and evaluates the direct and indirect role other cell types have in vessel and capillary formation. The article then analyses the different parameters researchers can modulate in a co-culture system in order to design optimal tissue-engineered constructs to match desired clinical applications.
- ItemNanocarriers in photodynamic therapy—in vitro and in vivo studies(Malden, MA : Wiley-Blackwell, 2019) Sztandera, Krzysztof; Gorzkiewicz, Michał; Klajnert‐Maculewicz, BarbaraPhotodynamic therapy (PDT) is a minimally invasive technique which has proven to be successful in the treatment of several types of tumors. This relatively simple method exploits three inseparable elements: phototoxic compound (photosensitizer [PS]), light source, and oxygen. Upon irradiation by light with specified wavelength, PS generates reactive oxygen species, which starts the cascade of reactions leading to cell death. The positive therapeutic outcome of PDT may be limited due to several aspects, including low water solubility of PSs, hampering their effective administration and blood circulation, as well as low tumor specificity, inefficient cellular uptake and activation energies requiring prolonged illumination times. One of the promising approaches to overcome these obstacles involves the use of carrier systems modulating pharmacokinetics and pharmacodynamics of the PSs. In the present review, we summarized current in vitro and in vivo studies regarding the use of nanoparticles as potential delivery devices for PSs to enhance their cellular uptake and cytotoxic properties, and thus—the therapeutic outcome of PDT.