Patent Application
20170274218
The present invention generally relates to photopolymerization devices and more particularly to devices that use light to harden, activate, control or change the chemical and physical state of a photo-chemically active or responsive material, as well as methods of using thereof.
Medical implants are used to replace impaired parts of the human or animal body. Usually a preformed material is placed inside the body and mechanically fixed to bone or soft tissue. In most cases such interventions are highly invasive. One option to reduce this invasiveness is to inject the entire implant (or a part of it) in liquid form and then harden the material in situ by a chemical reaction. However, these chemical reactions are usually hard to control, often impossible to stop, heat up surrounding tissue or require toxic additives. To sidestep such issues photo-active materials such as photopolymers are an attractive solution. Once injected they are illuminated with light in the visible or ultraviolet spectrum. The absorbed photons change the energy levels of electrons which then trigger the chemical reaction by creating free radicals, cations or anions. At the same time a fraction of the electrons relaxes back to the ground state, hence creating fluorescence which spectrum and intensity indicates the state of the chemical reaction.
However, to place such materials in a minimally invasive way it is necessary to access the body part with an injective device, a light source and a monitoring device. The current injection devices cannot be integrated into an illumination and monitoring system or vice versa. All-in-one integrated and ergonomic systems with a small diameter (e.g less than one 1 mm) are required. Moreover, methods have to be developed to ensure maximal adherence of implanted polymer to native tissue.
The present invention relates to a device structure and physical apparatus to photopolymerize or activate a photosensitive material and to monitor or control this process, using actinic light and a coupled analysis system which analyzes light coming from the photosensitive material to determine the degree of photopolymerization or activation of the photosensitive material during the photoactivation process.
In one aspect, the invention provides for an optical device, wherein said device is designed to interact with a photosensitive and/or a photocurable material, and wherein said device comprises a light source that emits actinic light, a tubular applicator having a proximal end and a distal end and an elongated shaft therebetween and containing at least one light-transmitting element adapted to bidirectionally transmit light between said proximal end and said distal end, wherein said proximal end of the applicator is operably connected to the light source; and wherein the distal end of the applicator is arranged to emit actinic light originated from the light source to the photocurable material and to capture light reflected or emitted by the photocurable material; and a light-guiding element which directs light travelling from the distal end of the applicator through the at least one light-transmitting element towards an optical detector, said optical detector being capable of detecting the light reflected or emitted by the photocurable material.
The apparatus according to the present disclosure comprises an optical system having one or several light sources, light-transmitting elements such as optical wave guides, light-guiding elements such as mirrors and/or beam combiners, free space and/or other optical subsystems to guide the light to the material to be illuminated. This optical system does not only guide the light to the material, but also collects the reflected, emitted or backscattered light from the material for monitoring purposes. Thus, the optical system also includes a subsystem to guide and finally evaluate such reflected/backscattered light. It consists of a dichroic beam-splitter and/or filter to separate the illumination and reflected/backscattered light, especially if the reflected/backscattered light is collected at the same position as the material is illuminated. Yet, it can also be completely separate e.g. consisting of a separate waveguide to collect the reflected and backscattered light.
In a preferred aspect, the light-transmitting elements of the illumination and monitoring device consist of optical fibers.
In one aspect, the light-guiding element includes beam splitter, band-pass filter and Bragg grating.
In one aspect, the light source emits light within a wavelength range of 200-3000 nanometers, preferably in a range of 200-700 nanometers, more preferably in a range of 315-700 nanometers.
The optical system also contains an analysis subsystem that may contain for instance a spectrometer to quantify fluorescence or Raman scattering or other types of back-reflected or back-scattered or emitted light, indicative of the state of the chemical or photochemical reaction. The light applied to and collected from the photosensitive material travels through an applicator having an elongated, tubular structure which allows photoactivation of materials on surfaces, in cavities, hollow recipients, tissues and within living organisms. In certain embodiments, the applicator is a cannula or a catheter containing optical fibers, connected to a light source and a spectrometer. Because the device is capable of characterizing the light-induced transformation of the photosensitive material in real time, optimal exposure of the photosensitive material to actinic light can be achieved, for example to obtain an optimal degree of polymerization and thus the best possible physical properties of a photopolymerized material for a specific purpose.
Another aspect of the invention lies in the combination of the illuminating and monitoring system with an injection system, allowing deposition of photosensitive material, illumination and monitoring through one single applicator. In addition to one or more light transmitting elements, such an applicator contains at least one channel through which a fluid photocurable or otherwise photosensitive material can be injected or deposited at a target site such as a cavity or a living organism's tissue. Therefore, in a further aspect, the invention provides for a system comprising an optical device as disclosed above, wherein the applicator is a tubular element having a wall and a lumen, and comprising at least one light-transmitting element placed within the lumen of the tubular element, and at least one interspace between said light-transmitting element and the internal side of the wall of said tubular element allowing the delivery of a photocurable fluid material through the distal end of the applicator into or onto a cavity or a tissue of a living host. In this context, the interspace can comprise a further injection device or at least a portion thereof; in an alternative or additional embodiment, the interspace coaxially surrounds the light-transmitting element, thus rendering the applicator itself a portion of the injection device. In an alternative or additional embodiment, the light-transmitting element and/or the injection device is incorporated within the applicator's wall. As will be evident to a person skilled in the relevant art, an injection device can comprise any kind of suitable pressure sources in order to apply a positive pressure on the liquid to be injected.
In a particular aspect, the device of the invention further comprises a subsystem to introduce one or more fluids to the interspace between the light-transmitting element and the wall of the tubular element at or close to the applicator's proximal end, said fluids once mixed constituting a photocurable fluid destined to be applied into or onto a cavity or a tissue of a living host. In addition, the photocurable material can be put and possibly held under pressure in order to increase adherence to the surrounding tissue or cavity wall.
In a preferred aspect, the applicator is a needle, a cannula, a catheter or an endoscopic arm.
In a preferred aspect, the photocurable material is a material that, once photocured, transforms from a fluid pre-polymeric condition to a polymeric, non-fluent condition.
In one aspect the intensity and illumination time of the light is adapted to affect (e.g. photocure) only injected material at a certain distance of the distal end. Thus, creating a controlled illuminated volume where injected material which is situated outside of this volume is not affected and can be, for instance, leave the body through the cardiovascular system. In addition such a volume can be further controlled during a surgery, by injecting and illuminating material in several steps and/or moving the optical light guide. Moreover, it can be combined with or consist of other elements limiting the light propagation and thus further controlling the volume activated by light. Such an element might be an additionally added element (such as a balloon) or an element which is part of the host (e.g. tissue wall).
It is among the general objects of the invention to also provide for techniques to effectively and efficiently applying a fluent polymerizable material to a target site, including living hosts' tissues, and for effecting polymerization of the fluent light-sensitive material in situ in an optimal way to obtain a desired degree of polymerization conferring to the applied material the best possible physical and/or chemical properties. To achieve such an optimal photopolymerization, the photopolymerization process is monitored and, for example, application of actinic light is stopped when the light emitted or reflected by the photopolymerized material indicates that the desired degree of polymerization has been reached. In addition, the light reflected by the photopolymerized material can not only indicate the material properties directly at the tip, but also at a certain depth within the material. For instance it can distinguish between whether the tip is surrounded by injected, photo-active material, by blood or by tissue. Or, if it is directly surrounded by injected material, but behind the material is tissue, the signal will vary depending on the distance the light travels through the injected material. Base on the signal the distance between probe and tissue or the thickness of the applied, injected material can be estimated.
In a further aspect, the invention thus provides for a method of applying, photocuring and monitoring a material into or onto a tissue or cavity, the method comprises applying from the applicator of the previously described system an initially entirely fluent, pre-polymeric photocurable material to the tissue or cavity, applying actinic light through at least one light-transmitting element to the photocurable material for a period of time sufficient to convert the entirely fluent, pre-polymeric photocurable material to a polymeric, non-fluent material, the polymeric, non-fluent material being in an amount effective to cover at least a portion of the target tissue and monitoring the curing process, wherein the initially entirely fluent, pre-polymeric photocurable material is applied into or onto the tissue or cavity through release from the distal end of said applicator, and wherein the at least one light-transmitting element further capture light reflected or emitted by the applied photocurable material and deliver said reflected or emitted light to a light-guiding element which directs light travelling from the distal end towards an optical detector, said optical detector being capable of detecting the light reflected or emitted by the photocurable material, and wherein monitoring the curing process involves analyzing a change in the properties of the light reflected or emitted by the photocurable material and detected by the optical detector, said change being a direct indication of the photocuring process itself.
When applied on living organisms such as animals, including human beings, a particular aspect of the invention relies in a method of replacing, healing or otherwise treating a damaged or altered organ or tissue in a living host by precisely injecting a photosensitive material, preferably in a minimally invasive way, to a target body site through the above-described method.
In one aspect, therefore, the tissue or cavity is a body tissue or body cavity. In a preferred aspect, the body tissue or body cavity is from an animal, including human beings. In a particular aspect, the method further comprises the step of introducing the applicator inside the animal body through surgical means or through an orifice.
In one aspect, the light delivery system is also used for imaging of the tissue.
In one aspect, the photocurable material is an implant, filler, tissue replacement, gel or scaffold applied to a living host. In a preferred aspect, the photocurable material is a biomaterial such as photo-responsive hydrogels (containing e.g. Polyethylen Glycol, Hyaluronans, methacrylates and the like), composite hydrogel (including e.g. cellulose fiber), gelatin-agar system, gel based on amino acids sequences derived from proteins, collagen, silk fibers, polyurethane, cellulose, poly vinyl alcohol or other poly- or copolymers, or curable or cross-linkable material.
In one aspect, photosensitizers sensible in the visible wavelength such as Riboflavin, Rose Bengal or Camphorquinone are used to induce the photochemical reaction. In another aspect photosensitizers in the ultraviolet range such as Irgacure 819 or Irgacure 2959 are used.
In one aspect a contrast agent such as Iodine based agents or other agents used in clinics for fluoroscopy, CT-scans or X-ray imaging is mixed to the injected material which allows to image the injected volume from outside of the animal or human body. Thus, the exact position of the material can be identified. Furthermore, leaking material can be traced or holes in tissue or bone can be closed (closed meaning that there is no leakage) by illuminating the material at the position where it leaks.
In at least one embodiment, the device and methods of the invention are used for treatment or prevention of a pathological condition or for cosmetic procedures.
In at least one embodiment, the device and methods of the invention are used to replace completely or partly an organ such as part of the intervertebral disc.
In at least one embodiment, the device and methods of the invention are used to replace, heal or strengthen cartilage tissues such as the articular cartilage of any joints or non-hyaline cartilage.
In at least one embodiment, the device and methods of the invention are used in dental applications such as for instance the injection and hardening of dental cement or hydrogels/composite hydrogels in a minimally invasive way.
In at least one embodiment, the device and methods of the invention are used for injection and photopolymerization of materials to treat aneurysms.
In at least one embodiment, the device and methods of the invention are used for cosmetic and esthetic surgery procedures. This could be augmentation mammoplasty or a treatment of glabellar lines by an injection similar to a treatment with Botulinum toxin A or hydrogel.
In at least one embodiment the invention relates to a method to inject, fix or otherwise position a photosensitive material comprising a drug or a pro-drug into or onto a cavity or a tissue in a controlled manner through the device of the invention. This could be for instance surgical methods to treat e.g. cancer where a material containing a (pro-)drug is placed close or into the cancerous tissue. The illumination with actinic light provided by the device is used to fix the material at a given location. In another embodiment the light photoactivates the drug as for example in phototherapy.
The present disclosure may be more readily understood by reference to the following detailed description presented in connection with the accompanying drawing figures, which form a part of this disclosure. It is to be understood that this disclosure is not limited to the specific conditions or parameters described and/or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed disclosure.
The applicator 105 has an elongated shape with a proximal end and a distal end. In the frame of the present disclosure, the word “applicator” refers to any tool or device used to apply an actinic light directly into or onto an area of interest. In at least some aspects, the applicator is a tubular element comprising at least one light-transmitting element such as for instance optical fibers. In one embodiment, the applicator consists of one or more light-transmitting elements which are designed to supply actinic light to the distal end of the applicator and to transmit returning light. In an alternative embodiment of the invention, the applicator has a body, connecting the proximal and distal ends, defining a lumen which contains the light-transmitting elements. The term “distal” refers to a direction toward the end of the device near where the light interacts with the photosensitive material; the term “proximal” refers to the opposite direction, that is, toward the optical detection and data analysis system. The body typically has a length between 0.5 and 500 cm. The body typically has a wall, which is usually made of a biocompatible and resilient metal. The wall is typically constructed from nitinol or stainless steel. In some embodiments, the applicator wall may be a commercially available syringe needle, catheter or a cannula. In yet another embodiment, the applicator may be an endoscope. In some embodiments, the distal end of the applicator may contain a needle. The light-transmitting elements contained in the applicator according to this embodiment of the invention may fill the entire lumen of the body of the applicator, or they may be bound to the wall with adhesive or fasteners or may be touching the wall or may be displaced axially from the wall with spacers, typically made from a resilient polymer. In some particular embodiments, the body of the applicator consists of a catheter or any suitable tubular element having a shape adaptable to the area within which it is inserted, such as for instance a blood vessel. An applicator according to this aspect of the invention may be of various size and shape, typically has a tubular shape, and is constructed of a soft, flexible, biocompatible material.
The system for illumination 103 of the subsystem 113 may comprise any known light sources capable of producing light with the desired temporal and frequency characteristics. System for illumination 103 may be, for example, solid-state lasers, gas lasers, dye lasers, or semiconductor lasers. System for illumination 103 may also be LED or other broadband sources, provided that the light sources are sufficiently powerful to drive the photocuring process. In some instances, the system for illumination 103 inherently provide short pulses of light at the desired frequency.
Due to parallel photorheology measurements, spectral analysis allows to link chemical changes in the material to mechanical parameters thereof, thus avoiding the analysis of the mechanical properties in situ by other means such as indentation. In addition, the spectral signature or the amount of backscattered light also gives information about the position or the environment of the distal tip for instance indicate if a thick tissue segment is blocking the exiting light and thus position of the distal end has to be adjusted.
In one embodiment, the light-transmitting element consists of several optical fibers. For example, one or several optical fibers 509 can be consecrated to illumination and one or several optical fibers 508 are used to collect the light. In at least some aspects, the optical fibers of the applicator can be arranged in several ways. For instance, fibers transmitting several or certain specific wavelenghts can be envisaged or fibers of different sizes can be assembled to guide the light to the distal end of the applicator and guide it back. In a particular embodiment depicted in
In one embodiment, 501 consists of several light sources, of which at least one provides the actinic light to photopolymerize the injected material and at least one provides actinic light at a different wavelength to record the state of the reaction.
F=f(t)
t being the time. By experimental tests a critical value Fc is found. Once this threshold is reached, the user interface emits a signal which indicates that the photopolymerization or chemical reaction has reached a certain degree or is completed. In addition, the information of several peaks or shifts can be evaluated at the same time to increase the precision of the monitoring for instance using reflected light around 750 nm to gather information about the reaction state of material further away from the distal end while using reflected light around 550 nm to access the reaction state closer to the distal end, thus:
F
i
=f
i(t)
t=f
i
−1(Fi)
i being the indices of one peak. And different functions fi and thresholds Fc,i can indicate different states of the reaction e.g.:
F
c,1
=F
1
=f
1(t1)
F
c,2
=F
2
=f
2(t2)
If F1 reaches the critical value Fc,1 a signal is emitted, in this case at t1. If F2 reaches the critical value Fc,2 a second signal is emitted, in this case at t2. The procedure is further illustrated in
This evaluation technique is based on fixing Fc,i experimentally. The obtained plot can be subsequently combined with previously performed photorheology measurements. Photorheology measures the elastic modulus (G) of a material in function (g) of the time and total intensity of the light illumination (I):
G=g(t, I)
Thus, by combining the spectroscopy data (F,f) and the photo rheology data (G,g), the mechanical properties are evaluated online by:
F=f(g−1(G, I))
or
G=g(f−1(F),I)
Furthermore, by testing layers of different thicknesses F can be correlated to an elastic modulus at a certain depth (Gd), thus indicating the state of polymerization at a given distance (d) of the probe:
G
d
=g
d(f−1(F), I)
The procedure can be further generalized and applied to several peaks (indexed with i):
G
d,i
=g
d,i(fi−1(Fi), I)
For example by tacking the changes of peak #1 the elastic modulus at a distance of the tip d0 (which could be for example 5 mm) is deduced:
G
d0,1
=g
d0,1(f1−1(F1),I)
Materials layers of serveal thickness (or at several depth) can be evaluated (
In case of a tissue layer blocking the exiting light the intensity
Finally, several peaks F1 and F2 can be compared and a critical value FC can be calculated for instance by dividing them (FC=F1/F2) or performing any other type of mathematical calculation.
The various channels of the injection subsystem may be stabilized within a housing that may be made essentially of a solid inert material and may comprise a holder to hold the device ergonomically during its use, such as for instance during surgery procedures. The light delivered by the light transmitting elements 205 is transmitted in both directions (dotted arrow), illuminating the injected material and back-propagating the light reflected or emitted by the illuminated material. Guiding elements 206 permit to align the light transmitting elements in the device while avoiding the block of the fluid flow (for example by not surrounding it completely in the radial plain).
In a particular embodiment, the device according to the present disclosure comprises a back-flow locking system, as shown in
In at least some embodiments, the photocurable material can therefore be a filling material such as a natural or synthetic material for strengthening, replacing, healing, reinforcing or otherwise treating living tissues such us bones. Suitable filling materials include glues, epoxies, adhesives, cements, hard tissue replacement polymers, biodegradable polymers and copolymers, and various other biomaterials known in the art for strengthening, replacing or reinforcing tissue. As inert materials, bone reinforcing mixtures may be incorporated into surrounding tissue or gradually replaced by original tissue. In some embodiments, the photocurable material may be a filling material such as composite hydrogels for strengthening, replacing, healing, reinforcing or otherwise treating a nucleus pulposus of an intervertebral disc such as for example methacrylate and poly(ethylene-glycol) based polymers in combination with a photoinitiator and possibly reinforced with fibers such as cellulose nanofibrils. Those skilled in the art will recognize that numerous variants of the above mentioned materials known in the art are within the scope of the presently disclosed embodiments.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2015/056718 | 9/3/2015 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62047095 | Sep 2014 | US |
