Towards Clinical Translation: Optimized Fabrication of Controlled Nanostructures on Implant-Relevant Curved Zirconium Surfaces

Anodization enables fabrication of controlled nanotopographies on Ti implants to offer tailorable bioactivity and local therapy. However, anodization of Zr implants to fabricate ZrO2 nanostructures remains underexplored and are limited to the modification of easy-to-manage flat Zr foils, which do not represent the shape of clinically used implants. In this pioneering study, we report extensive optimization of various nanostructures on implant-relevant micro-rough Zr curved surfaces, bringing this technology closer to clinical translation. Further, we explore the use of sonication to remove the top nanoporous layer to reveal the underlying nanotubes. Nano-engineered Zr surfaces can be applied towards enhancing the bioactivity and therapeutic potential of conventional Zr-based implants.

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Therapeutic potential of polypeptide-based conjugates: Rational design and analytical tools that can boost clinical translation

Advanced Drug Delivery Reviews ◽

10.1016/j.addr.2020.10.007 ◽

2020 ◽

Vol 160 ◽

pp. 136-169 ◽

Cited By ~ 1

Author(s):

Tetiana Melnyk ◽

Snežana Đorđević ◽

Inmaculada Conejos-Sánchez ◽

María J. Vicent

Keyword(s):

Rational Design ◽

Therapeutic Potential ◽

Clinical Translation ◽

Analytical Tools

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Critical Evaluation of the Interaction of Reactive Oxygen and Nitrogen Species with Blood to Inform the Clinical Translation of Nonthermal Plasma Therapy

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/9750206 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Abraham Lin ◽

Eline Biscop ◽

Colum Breen ◽

Stephen J. Butler ◽

Evelien Smits ◽

...

Keyword(s):

Whole Blood ◽

Therapeutic Potential ◽

Ambient Pressure ◽

Critical Evaluation ◽

Reactive Oxygen ◽

Clinical Translation ◽

Therapeutic Effects ◽

Nitrogen Species ◽

Preclinical Research ◽

Over Time

Non-thermal plasma (NTP), an ionized gas generated at ambient pressure and temperature, has been an emerging technology for medical applications. Through controlled delivery of reactive oxygen and nitrogen species (ROS/RNS), NTP can elicit hormetic cellular responses, thus stimulating broad therapeutic effects. To enable clinical translation of the promising preclinical research into NTP therapy, a deeper understanding of NTP interactions with clinical substrates is profoundly needed. Since NTP-generated ROS/RNS will inevitably interact with blood in several clinical contexts, understanding their stability in this system is crucial. In this study, two medically relevant NTP delivery modalities were used to assess the stability of NTP-generated ROS/RNS in three aqueous solutions with increasing organic complexities: phosphate-buffered saline (PBS), blood plasma (BP), and processed whole blood. NTP-generated RNS collectively (NO2−, ONOO−), H2O2, and ONOO− exclusively were analyzed over time. We demonstrated that NTP-generated RNS and H2O2 were stable in PBS but scavenged by different components of the blood. While RNS remained stable in BP after initial scavenging effects, it was completely reduced in processed whole blood. On the other hand, H2O2 was completely scavenged in both liquids over time. Our previously developed luminescent probe europium(III) was used for precision measurement of ONOO− concentration. NTP-generated ONOO− was detected in all three liquids for up to at least 30 seconds, thus highlighting its therapeutic potential. Based on our results, we discussed the necessary considerations to choose the most optimal NTP modality for delivery of ROS/RNS to and via blood in the clinical context.

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Stem cell transplantation for amyotrophic lateral sclerosis: therapeutic potential and perspectives on clinical translation

Cellular and Molecular Life Sciences ◽

10.1007/s00018-014-1613-4 ◽

2014 ◽

Vol 71 (17) ◽

pp. 3257-3268 ◽

Cited By ~ 25

Author(s):

Irene Faravelli ◽

Giulietta Riboldi ◽

Monica Nizzardo ◽

Chiara Simone ◽

Chiara Zanetta ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Therapeutic Potential ◽

Clinical Translation ◽

Lateral Sclerosis

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Mesenchymal stromal cells: what have we learned so far about their therapeutic potential and mechanisms of action?

Emerging Topics in Life Sciences ◽

10.1042/etls20210013 ◽

2021 ◽

Author(s):

Francesco Amadeo ◽

Katherine Trivino Cepeda ◽

James Littlewood ◽

Bettina Wilm ◽

Arthur Taylor ◽

...

Keyword(s):

Animal Models ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Animal Studies ◽

Therapeutic Potential ◽

Animal Experiments ◽

Mechanisms Of Action ◽

Clinical Translation ◽

Beneficial Effects ◽

Wide Range

Mesenchymal stromal cells (MSCs) have been found to be safe and effective in a wide range of animal models of human disease. MSCs have been tested in thousands of clinical trials, but results show that while these cells appear to be safe, they tend to lack efficacy. This has raised questions about whether animal models are useful for predicting efficacy in patients. However, a problem with animal studies is that there is a lack of standardisation in the models and MSC therapy regimes used; there appears to be publication bias towards studies reporting positive outcomes; and the reproducibility of results from animal experiments tends not to be confirmed prior to clinical translation. A further problem is that while some progress has been made towards investigating the mechanisms of action (MoA) of MSCs, we still fail to understand how they work. To make progress, it is important to ensure that prior to clinical translation, the beneficial effects of MSCs in animal studies are real and can be repeated by independent research groups. We also need to understand the MoA of MSCs to assess whether their effects are likely to be beneficial across different species. In this review, we give an overview of the current clinical picture of MSC therapies and discuss what we have learned from animal studies. We also give a comprehensive update of what we know about the MoA of MSCs, particularly in relation to their role in immunomodulation.

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