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Researchers design biomedical devices with natural fluorescence for their monitoring in the body

4 Jun '19 | By Biophotonics.World
Researchers design biomedical devices with natural fluorescence for their monitoring in the body
Figure 1. Alginate capsules with genipin crosslinked double poly-L-Lysine (GDP) membranes emit natural, intense and stable fluorescence in the far-red range. When increasing doses of capsules are injected subcutaneously in mice, good linearity of signal to microcapsule dose can be detected over several weeks.
By: Prof. José Luis Pedraz

Researchers from the University of the Basque Country (UPV/EHU) and the University of Michigan (UM) have developed a cell immunoisolation device (microcapsules) with intrinsic capacity to be monitored once implanted in the organism. The work has been selected as the cover of the Journal of Biophotonics for the month of April, one of the most important international journals in the field of application of photonic technologies in biomedicine.

Researchers of the NanoBioCel group from the University of the Basque Country / Euskal Herriko Unibertsitatea (Spain), together with The Luker Lab from the University of Michigan (USA), have developed a cell immunoisolation device (microcapsules) with intrinsic capacity to be tracked once implanted in the organism. The novel design incorporates a natural substance called genipin, which emits intense and stable fluorescence in the far-red range.

Non-invasive monitoring of implanted hydrogel-based biosystems generally requires indirect marking of the vehicle or load, which increases the complexity and the potential risk of altering its functionality. For the first time, this group of researchers has shown that hydrogel-based biosystems can be produced from biomaterials with intrinsic properties for non-invasive monitoring, in this case, through the use of genipin.

"It is important to note that to date no one has exploited the natural fluorescence emitted by the genipin as a non-invasive monitoring system in cell therapies implanted in living beings" -the researchers point out-. "As a first milestone in this regard, we have developed a novel immunoisolation device that incorporates the genipin in its own design, thus being traceable once implanted in the body. Through a fast, efficient and non-cytotoxic procedure, we have managed to maximize the fluorescence of the microcapsules until achieving an excellent signal-to-noise ratio. In addition, we have validated the use of genipin as a quantitative image probe, demonstrating that it is possible to obtain an intense and stable fluorescence with good signal linearity versus implanted microcapsule dose over several weeks. Through this strategy, we have been able to evaluate the actual injected dose immediately after administration and control its position over time, which significantly improves the biosafety and effectiveness of the therapy. "

Cell microencapsulation is a technology with great potential for the treatment of several chronic disorders ranging from diabetes to cancer. The cells of therapeutic interest are included in biocompatible polymer matrices that allow the access of nutrients and oxygen to the interior, as well as the outward diffusion of the different therapeutic compounds. In recent years, the great advances made in the area of ​​cell microencapsulation have turned this technology into something more than a mere promise, leading to the development of designs for various disorders and diseases, as well as for numerous approaches to tissue engineering. A wide range of cell types (from genetically engineered cell lines to mesenchymal stem cells) have been successfully introduced into biocompatible immobilization devices capable of controlling the bidirectional diffusion of molecules. These encapsulated cells are used to secrete hormones, neurotransmitters and growth factors, among others, for long periods of time, reducing or even avoiding immunosuppression protocols.

Therefore, we believe that our approach may help to promote the definitive clinical translation of cell encapsulation technologies by significantly improving their biosafety and efficacy. In addition, the idea may have a potential successful application in the industry of hydrogel-based nano, micro and macro technologies. These are called to be fundamental pieces both for biomedical research and for the advancement of clinical medicine through applications such as tissue engineering and regenerative medicine. In particular, this finding may inspire many other researchers to non-invasively monitor different clinical processes such as biodistribution, degradation or the status of implantable hydrogel-base technologies. "As fluorescence imaging systems are gradually implemented in clinical practice, we believe that our proposal could have a successful applicability in the advancement of multiple biotechnologies, including drug and cell delivery systems, vaccines or biosensors, "they conclude.

Bibliographic reference

Edorta Santos‐Vizcaino, Henry Haley, Ainhoa Gonzalez‐Pujana, Gorka Orive, Rosa Maria Hernandez, Gary D. Luker, Jose Luis Pedraz

Monitoring implantable immunoisolation devices with intrinsic fluorescence of genipin

Journal of Biophotonics (April 2019)

DOI: https://doi.org/10.1002/jbio.201800170

Contact and further information: 

Prof. José Luis Pedraz: joseluis.pedraz@ehu.eus

Prof. Gary D. Luker: gluker@med.umich.edu

Area of application: Cellular biotechnology, Cell Biology

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