Photopolymerization is a common method to harden materials initially in a liquid state. A surgeon can directly trigger
the solidification of a dental implant or a bone or tissue filler by using ultra-violet light. Traditionally,
photopolymerization has been used mainly in dentistry. Over the last decade advances in material development including
a wide range of biocompatible gel- and cement-systems open up a new avenue for in-situ photopolymerization.
We designed a miniaturized light probe where a photoactive material can be 1) mixed, pressurized and injected 2)
photopolymerized or photoactivated and 3) monitored during the chemical reaction. The device enables surgeries to be
conducted through a hole smaller than 500 μm in diameter.
Using a combination of Raman and fluorescence spectroscopy, the current state of the photopolymerization was inferred
and monitored in real time within an in-vitro tissue model. It was also possible to determine roughly the position of the
probe within the tissue cavity by analysing the fluorescence signal. Using the technique hydrogels were successfully
implanted into a bovine intervertebral disc model. Mechanical tests could not obstruct the functionality of the implant.
Finally, the device was also used for other application such as the implantation of a hydrogel into an aneurysm tissue
cavity which will be presented at the conference.
Photopolymerization is a common method to cure materials initially in a liquid state, such as dental implants or bone or tissue fillers. Recent advances in the development of biocompatible gel- and cement-systems open up an avenue for in situ photopolymerization. For minimally invasive surgery, such procedures require miniaturized surgical endoscopic probes to activate and control photopolymerization in situ. We present a miniaturized light probe in which a photoactive material can be (1) mixed, pressurized, and injected, (2) photopolymerized/photoactivated, and (3) monitored during the chemical reaction. The device is used to implant and cure poly(ethylene glycol) dimethacrylate-hydrogel-precursor in situ with ultraviolet A (UVA) light (365 nm) while the polymerization reaction is monitored in real time by collecting the fluorescence and Raman signals generated by the 532-nm excitation light source. Hydrogels could be delivered, photopolymerized, and monitored by the probe up to a curing depth of 4 cm. The size of the photopolymerized samples could be correlated to the fluorescent signal collected by the probe, and the reproducibility of the procedure could be demonstrated. The position of the probe tip inside a bovine caudal intervertebral disc could be estimated in vitro based on the collected fluorescence and Raman signal.
Currently implants or tissue replacements are inserted either as a whole implant or by injecting a liquid which polymerizes to form a solid implant at the appropriate location. This is either highly invasive or not controllable. We developed a tool to perform such surgeries in a minimally invasive and controllable way. It combines photopolymerization and fluorescence spectroscopy in a surgical apparatus. However, to successfully replace tissue such as cartilage or an intervertebral disc, photopolymerizable materials do not only need to be photoactive. They should also be able to withstand the environmental loading conditions after implantation. Therefore we developed a set of in situ and in vitro tests adapted to the evaluation of photopolymerized tissue replacements and implants. In particular in this article, we report on a method, which combines photopolymerization and photorheology to track the current state of polymer during photopolymerization.
Photopolymerization is a common tool to harden materials initially in a liquid state. A surgeon can directly trigger the solidification of a dental implant or a bone or tissue filler simply by illumination. Traditionally, photopolymerization has been used mainly in dentistry. Over the last decade advances in material development including a wide range of biocompatible gel- and cement-systems open up a new avenue for in-situ photopolymerization.
However, at the device level, surgical endoscopic probes are required. We present a miniaturized light probe where a photoactive material can be 1) mixed, pressurized and injected 2) photopolymerized or photoactivated and 3) monitored during the chemical reaction. The device enables surgeries to be conducted through a hole smaller than 1 mm in diameter.
Beside basic injection mechanics, the tool consists of an optical fiber guiding the light required for photopolymerization and for chemical analysis. Combining photorheology and fluorescence spectroscopy, the current state of the photopolymerization is inferred and monitored in real time. Biocompatible and highly tuneable Poly-Ethylene-Glycol (PEG) hydrogels were used as the injection material.
The device was tested on a model for intervertebral disc replacement. Gels were successfully implanted into a bovine caudal model and mechanically tested in-vitro during two weeks. The photopolymerized gel was evaluated at the tissue level (adherence and mechanical properties of the implant), at the cellular level (biocompatibility and cytotoxicity) and ergonomic level (sterilization procedure and feasibility study).
This paper covers the monitoring aspect of the device.
Photopolymerization is commonly used in a broad range of bioapplications, such as drug delivery, tissue engineering, and surgical implants, where liquid materials are injected and then hardened by means of illumination to create a solid polymer network. However, photopolymerization using a probe, e.g., needle guiding both the liquid and the curing illumination, has not been thoroughly investigated. We present a Monte Carlo model that takes into account the dynamic absorption and scattering parameters as well as solid–liquid boundaries of the photopolymer to yield the shape and volume of minimally invasively injected, photopolymerized hydrogels. In the first part of the article, our model is validated using a set of well-known poly(ethylene glycol) dimethacrylate hydrogels showing an excellent agreement between simulated and experimental volume-growth-rates. In the second part, in situ experimental results and simulations for photopolymerization in tissue cavities are presented. It was found that a cavity with a volume of 152 mm 3 can be photopolymerized from the output of a 0.28-mm 2 fiber by adding scattering lipid particles while only a volume of 38 mm 3 (25%) was achieved without particles. The proposed model provides a simple and robust method to solve complex photopolymerization problems, where the dimension of the light source is much smaller than the volume of the photopolymerizable hydrogel.
Andreas Schmocker, Azadeh Khoushabi, Benjamin Gantenbein-Ritter, Samantha Chan, Harald Marcel Bonél, Pierre-Etienne Bourban, Jan Anders Månson, Constantin Schizas, Dominique Pioletti, Christophe Moser
Photopolymerized hydrogels are commonly used for a broad range of biomedical applications. As long as the polymer volume is accessible, gels can easily be hardened using light illumination. However, in clinics, especially for minimally invasive surgery, it becomes highly challenging to control photopolymerization. The ratios between polymerizationvolume and radiating-surface-area are several orders of magnitude higher than for ex-vivo settings. Also tissue scattering occurs and influences the reaction. We developed a Monte Carlo model for photopolymerization, which takes into account the solid/liquid phase changes, moving solid/liquid-boundaries and refraction on these boundaries as well as tissue scattering in arbitrarily designable tissue cavities. The model provides a tool to tailor both the light probe and the scattering/absorption properties of the photopolymer for applications such as medical implants or tissue replacements. Based on the simulations, we have previously shown that by adding scattering additives to the liquid monomer, the photopolymerized volume was considerably increased. In this study, we have used bovine intervertebral disc cavities, as a model for spinal degeneration, to study photopolymerization in-vitro. The cavity is created by enzyme digestion. Using a custom designed probe, hydrogels were injected and photopolymerized. Magnetic resonance imaging (MRI) and visual inspection tools were employed to investigate the successful photopolymerization outcomes. The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels.
We report on the modeling of a photopolymerizable hydrogel and its application as a replacement of the interior of the intervertebral disc (so called Nucleus Pulposus). The hydrogel is initially injected in its liquid form and then photopolymerized via a small catheter. Therefore, also the light necessary for the photopolymerization is constrained to a small light guide to keep the surgical procedure as minimally invasive as possible. Hence, the hydrogel is photopolymerized inside.
For applications with restricted physical access and illumination time, such as an Nucleus Pulposus replacement, photopolymerization of volumes with a large volume/illumination-area ratio becomes highly challenging. During polymerization, the material’s absorption and scattering coefficients change and directly influence local polymerization rates. By understanding and controlling such polymerization patterns, local material properties can be engineered (e.g. elastic modulus, swelling ratio), to match the set of mechanical requirements for the implant. Thus, it is essential to better understand and model photopolymerization reactions.
Experiments were conducted by polymerizing a hydrogel in a column-like volume using an optical fiber for light delivery. Quantitative scattering and absorption values as well as monomer conversion rates of the hydrogel sample were validated using a newly established Monte Carlo model for photopolymerization. The results were used to study and predict 3D polymerization patterns for different illumination configurations. In particular, we show an example of a lumbar intervertebral disc replacement where the jelly core of the intervertebral disc (Nucleus Pulposus) is replaced by an in situ photopolymerized hydrogel.
The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels.
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