Abstract:
The present invention relates to a device to photocure and/or photoactivate a photosensitive material. The device comprises several subsystems to transmit light towards an area of interest where a photosensitive material is applied as well as to collect light reflected by the applied photosensitive material. Reflected light is analyzed by an optical detector to monitor the photocuring and/or photoactivation process. Further means to inject or otherwise apply a photosensitive material can be combined in the same device. Methods for applying a fluent polymerizable material to a target site and for effecting polymerization of the fluent light-sensitive material in situ are also disclosed.

Description:
FIELD OF THE INVENTION 
       [0001]    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. 
       BACKGROUND 
       [0002]    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. 
         [0003]    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. 
       SUMMARY OF THE INVENTION 
       [0004]    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. 
         [0005]    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. 
         [0006]    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. 
         [0007]    In a preferred aspect, the light-transmitting elements of the illumination and monitoring device consist of optical fibers. 
         [0008]    In one aspect, the light-guiding element includes beam splitter, band-pass filter and Bragg grating. 
         [0009]    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. 
         [0010]    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. 
         [0011]    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&#39;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&#39;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. 
         [0012]    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&#39;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. 
         [0013]    In a preferred aspect, the applicator is a needle, a cannula, a catheter or an endoscopic arm. 
         [0014]    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. 
         [0015]    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). 
         [0016]    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&#39; 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. 
         [0017]    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. 
         [0018]    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. 
         [0019]    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. 
         [0020]    In one aspect, the light delivery system is also used for imaging of the tissue. 
         [0021]    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. 
         [0022]    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. 
         [0023]    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. 
         [0024]    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. 
         [0025]    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. 
         [0026]    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. 
         [0027]    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. 
         [0028]    In at least one embodiment, the device and methods of the invention are used for injection and photopolymerization of materials to treat aneurysms. 
         [0029]    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. 
         [0030]    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. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0031]      FIG. 1  is a conceptual overview of the device and its subsystems. 
           [0032]      FIG. 2  is a conceptual view of the optical subsystems for illumination and monitoring. 
           [0033]      FIG. 3  illustrates the phenomena underlying the online data analysis, including change in spectra due to photopolymerization and comparison to photorheology data. 
           [0034]      FIG. 4  depicts the combination of injection system and optical light guide in a preferred embodiment allowing for the mixing of two fluid materials and the flow of these materials along an optical fiber. Solid arrows indicate flow of liquid material; dashed arrows indicate light propagation. 
           [0035]      FIG. 5  illustrates the insertion of the tip of the applicator into a cavity or tissue. Fine solid arrows indicate material flow; dashed arrows indicate light propagation, absorption and scattering. 
           [0036]      FIG. 6  illustrates the flow locking system of some embodiments. 
           [0037]      FIG. 7  Illustrates how the injection and photopolymerization method may increase adherence of a photopolymerizable material to a cavity. 
           [0038]      FIG. 8  Illustrates how a cavity is created artificially 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0039]    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. 
         [0040]      FIG. 1  is an illustration of two possible embodiments of a device according to the present disclosure.  FIG. 1 a    illustrates a schematic overview of a device comprising at least two functionalities: illumination of a material deposited in a cavity or body tissue  112 , and analysis of light that is reflected by or emitted by the illuminated material. To achieve this, the device comprises  3  functional units: an illumination system  103  capable of emitting actinic light, an optical detection and data analysis system  104  suited to analyze light coming from the illuminated material, and a system  105 , termed applicator, that allows the targeted application and collection of light to or from a material deposited in a cavity or body tissue. The device consists of at least 2 physical subsystems including a casing  113  comprising a source of actinic light  103  and an optical detection and data analysis system  104 ; and an applicator  105  that combines the possibility to deliver actinic light to a cavity or body tissue  112  in order to activate or photocure a suitable applied photosensitive or photocurable material and to collect light that is reflected, backscattered or emitted by the material illuminated with actinic light. The light coming from the illuminated material is guided to the optical detection and data analysis system  104  allowing real time monitoring of the photoactivation or photocuring process. The terms “photoactivation” refers to a chemical change a photosensitive material undergoes when illuminated with actinic light, said chemical change providing said material with one or more new functionalities. The terms “photocuring”, “curing”, “photopolymerization”, and the like are herein used interchangeably and refer to the toughening or hardening of a material by cross-linking of polymer chains or to the formation of a new polymer-based material by linking several monomers. Such photocurable materials are polymerized upon exposure to electromagnetic radiation, i.e., light. The light may be microwave, infrared, visible, or ultraviolet light, most typically visible or near ultraviolet. “Actinic light” refers to the kind of light to which a particular photosensitive material is sensitive; in other words, actinic light has the capacity to activate, polymerize or somehow alter the properties of a particular photosensitive material. The term “reflection” or “backscattering” includes specular and diffuse reflection including backscattering. The term “reflected” or “backscattered” refers to radiation reflected by specular or diffuse reflection including backscattering. Specular meaning that the reflected light can have a different wavelength than the illumination light such as for instance for Raman scattering or the emission of fluorescence or phosphorescence. 
         [0041]    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. 
         [0042]    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. 
         [0043]      FIG. 1 b    illustrates a schematic overview of a device comprising at least 3 functionalities: illumination and light analysis as described above, and injection of a photocurable or photoactivatable material into a cavity or body tissue  112 . In this case, the applicator  105  has a lumen or one or more channels running throughout the entire length through which a fluid material can flow to the distal end (hereinafter, “tip”) of the applicator. At or near the proximal end of the applicator, fluid materials can be injected via an injection subsystem  102 . In combination with the applicator, the injection subsystem is disposed to cause the injected liquid material to flow into and through the applicator leaving it at its distal end where it flows into a cavity  112 , onto a surface or to its final location. 
         [0044]      FIG. 2 a    depicts a preferred embodiment of illumination and data analysis subsystem  113  and a cross-section of the applicator  105 . A lightsource  501  with one or several excitation wavelength emits a light beam  100  which is collimated by a lens  502 . The lightsource  501  can for instance consist of a laser, a LED and second laser which are combined using a dichroic mirrors. The light beam crosses a wavelength-sensitive beam-splitter  503  and is focused onto light-transmitting elements contained within the applicator  105  by a second lens  504 . The so obtained actinic light is guided forward through the light-transmitting element until it exits the device from the applicator&#39;s distal end. Once actinic light interacts with a photocurable material, the obtained, back-scattered light is guided from the distal to the proximal end of the applicator where it leaves the light-transmitting element, is collimated by the lens  504  and impinges onto the beam-splitter  503 . Photons having a different wavelength or any specific wavelength of interest are reflected by the beam-splitter  503  and focused by a third lens  505  to a monitoring system for data analysis  506 , for example a spectral analyzer. Spectral analysis is useful for determining the change of physical and chemical status of the photocurable material. One of the advantages of the system of the present invention is the possibility to monitor the process in real time and therefore tailor the photocuring of the applied material accordingly. During the photopolymerization process brought about by actinic light, an initial low viscosity fluid material will typically have a different spectral signature after its photopolymerization during which its crosslink density or polymerization degree increase. This difference allows to discriminate between a less and a more crosslinked and polymerized material and thus to follow the kinetics of the material property changes, being its viscosity or other physical properties related to the molecular structure of the polymer or illuminated material. 
         [0045]    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. 
         [0046]    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  FIG. 2 b   , the light-transmitting element  509  is directly connected to the light source  501  and the spectral analyzer  506  is directly connected to the collection fibers  508 . 
         [0047]    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. 
         [0048]      FIG. 3  shows the reflected spectrum recorded over time by a monitoring system for data analysis  506 , which in one specific embodiment is a spectrometer. Using the information of the backscattered light, the spectrum gives information on the position or environment of the applicator and indicates whether the applicator is surrounded by tissue or photocurable/photocured polymeric material. Throughout photopolymerization different shifts can be observed: the spectra shifts laterally in function of wavelength or vertically in function of intensity. It is possible that the entire spectra or only one or several peaks shift over time. The change is measured by defining vertical or horizontal axes. Thus a time-intensity plot is created. The change in intensity or wavelength (F) of the spectra or the one of the peaks can be described as using a function f: 
         [0000]        F=f ( t ) 
         [0000]    t being the time. By experimental tests a critical value F c  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: 
         [0000]        F   i   =f   i ( t ) 
       Or 
       [0049]        t=f   i   −1 ( F   i ) 
         [0000]    i being the indices of one peak. And different functions f i  and thresholds F c,i  can indicate different states of the reaction e.g.: 
         [0000]        F   c,1   =F   1   =f   1 ( t   1 ) 
         [0000]        F   c,2   =F   2   =f   2 ( t   2 ) 
         [0050]    If F 1  reaches the critical value F c,1  a signal is emitted, in this case at t 1 . If F 2  reaches the critical value F c,2  a second signal is emitted, in this case at t 2 . The procedure is further illustrated in  FIG. 3 d   ) and  f ). 
         [0051]    This evaluation technique is based on fixing F c,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): 
         [0000]        G=g ( t, I ) 
         [0052]    Thus, by combining the spectroscopy data (F,f) and the photo rheology data (G,g), the mechanical properties are evaluated online by: 
         [0000]        F=f ( g   −1 ( G, I )) 
         [0000]    or 
         [0000]        G=g ( f   −1 ( F ), I ) 
         [0053]    Furthermore, by testing layers of different thicknesses F can be correlated to an elastic modulus at a certain depth (G d ), thus indicating the state of polymerization at a given distance (d) of the probe: 
         [0000]        G   d   =g   d ( f   −1 ( F ),  I ) 
         [0054]    The procedure can be further generalized and applied to several peaks (indexed with i): 
         [0000]        G   d,i   =g   d,i ( f   i   −1 ( F   i ),  I ) 
         [0055]    For example by tacking the changes of peak # 1  the elastic modulus at a distance of the tip d 0  (which could be for example 5 mm) is deduced: 
         [0000]        G   d0,1   =g   d0,1 ( f   1   −1 ( F   1 ), I ) 
         [0056]    Materials layers of serveal thickness (or at several depth) can be evaluated ( FIG. 3 f   ) 
         [0057]    In case of a tissue layer blocking the exiting light the intensity  FIG. 3 a    would suddenly increase (several orders of magnitude are possible) and the spectra would also change in function of wavelength. As certain tissues have a given reflection spectra when illuminated with light such reflections can be used to further give information (e.g. about the type of material in front of the tip—for instance tissue, blood or injected material) to the operator (e.g. surgeon) when performing an operation. 
         [0058]    Finally, several peaks F 1  and F 2  can be compared and a critical value F C  can be calculated for instance by dividing them (F C =F 1 /F 2 ) or performing any other type of mathematical calculation. 
         [0059]      FIG. 4  is a cut view of the injection subsystem  102  according to one embodiment of the invention. Two mechanisms are responsible for combining the injection and illumination functionalities: there is a type of crossing where a fluid material can be brought close to the light transmitting element  205 , along which the fluid material will flow towards the tip of the applicator. In this particular embodiment, the device consists of several injection channels (for the sake of simplicity, only two channels  201  and  202  are depicted in  FIG. 4 ), an outflow channel  203  and a fiber channel  204 . The injection channels can be aligned in an arbitrary way. The outflow channel  203  and the fiber channel  204  have to be sufficiently collinearly aligned not to over bend the light transmitting elements  205  which are typically optical fibers. The light transmitting elements  205  are inserted through the fiber channel  204  and leave the injection subsystem  102  through the outflow channel  203 . The injected material can flow in both directions in the injection channels (solid arrows). The injection subsystem  102  is either an integrated part of the applicator or a separate entity connected to the applicator via the outflow and fiber channels. In either case the outflow channel  203  is connected to the distal end of the applicator where the photoactivable fluid material is ejected out of the device. In one embodiment, more than one fluid material can be delivered within the applicator through the injection channels  201 ,  202 . These fluid materials are mixed once in the applicator, thus permitting for instance the constitution of a photocurable material starting from two or more non-photocurable materials. 
         [0060]    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). 
         [0061]      FIG. 5  shows the mode of action of a particular embodiment of the device according to the present invention. The tip of the applicator is inserted into a tissue cavity  112  surrounded by the remaining tissue  301 , such as for instance a bone cavity surrounded by bone. The cavity  112  can be closed as illustrated in  FIG. 5 a   , and can be for instance missing nucleus pulposus of an intervertebral disc, but it can also be a surface or hole such as a bone void to which the distal end of the applicator is brought to. The applicator of the device comprises a body  302  such as a solid or flexible cannula and one or more optical fibers  205  as light-transmitting elements. A fluid, photocurable material (solid arrows) pushed under an external force, flows through the outflow channels  203  which in this embodiment are interspaces between the light-transmitting element and the internal side of the applicator&#39;s body wall  302 , into the cavity  112 . The light (dotted arrow) guided into the optical fibers impinges onto the injected material where it is absorbed or scattered into different directions and then absorbed elsewhere. Some photons are also reflected or back-scattered and back-propagated through the light-transmitting element  205 . In one embodiment, the applicator consisting of a cannula and an optical fiber, the tip of the cannula  302  and the tip of the light-transmitting element  205  can be placed at the same height or at a given distance. In one embodiment, the light-transmitting element can be inserted before or during the use of the device, and it can be moved forward ( FIG. 5 b   , solid arrow) or backward and possibly laterally within the applicator during the procedure. In another embodiment in which the applicator comprises a cannula, the tip of the light-transmitting element  205  and the cannula can be flat or sharpened with a given angle  304  ( FIG. 5 c   ). In a particular embodiment, this angle can be different for the cannula and the fiber. In one embodiment, the light-transmitting element and the applicator&#39;s body can touch each other ( 305 ) or move freely ( 307 ), and they can have the same or a different curvature ( 306 ) ( FIG. 5 d   ). The use of other kind of tips for the light guide (e.g. implemented lens, ball lens, diffuser, conical shape, side-fire tip, transparent balloon tip, etc.) can be used. 
         [0062]    In a particular embodiment, the device according to the present disclosure comprises a back-flow locking system, as shown in  FIG. 6 . At the end of the fiber channel  204  a screw-tap with hole  401  is screwed into the housing of the injection subsystem. The tap has a hole in the middle to insert the light-transmitting element  205  and it can be guided by lateral joints  403 . Between the screw-tap and the device a rubber ring  402  is placed. When the screw-tap is screwed into the device the ring starts to act as a valve. It deforms and locks at the same time the space between ring and device ( 404 ), ring/screw-tap ( 405 ) and ring/optical fiber ( 406 ). Thus any backward outflow through the channel  204  is inhibited and the fluid inside the device can be pressurized up to 50 bar. 
         [0063]      FIG. 7  depicts a particular embodiment of the invention in which a fluid, non-polymerized material is directly injected into a body tissue having pores, (micro)cavities and/or voids such as the bone tissue. The tip of the applicator is put within or in close proximity with the porous or hollow tissue structure. This can be achieved through surgical meanings, such as for instance via a pre-formed bone drill wherein the applicator is inserted. The photocurable fluid, non-polymerized material flows through the interspace  203  between the optical fiber elements  205  and the internal side of the wall of the applicator under an applied pressure via e.g. an injecting system or simply a syringe. These syringes may be used to inject the fluid material, but they can also be used for mixing several materials together or increase the pressure to a given level during injection. They can be plugged in or screwed onto the device. They can be fix or removable parts of the device, specifically designed and adapted to the viscosity of the injected materials and the medical method, or they can be commercially available syringes. The pressurization and its viscosity allow the fluid, non-polymerized material to flow into macro- ( 701 ) and microscopic ( 704 ) pores of the tissue or bone  301 . The pressure, preferably between 0 and 50 bar, and the viscosity, preferably between 10 −5  and 1 [Pa s] or also higher, are key elements to increase the adherence of the fluid, non-polymerized material with the surrounding tissue it was injected in. Once injected, or alternatively during injection, the light can initiate the photopolymerization reaction by directly illuminating the pore  702  or also by being transmitted and scattered through the tissue  703 , thus permitting the change of physical status of the fluid, non-polymerized material to a non-fluent (or solid), polymerized material. Once a polymerized material is created in the cavity, it physically blocks the macro-pore  701 . The same type of entanglement can be created in micro-pores  704  which have a similar size of the polymer chains  705 : due to its completely unpolymerized state and the applied pressure, the chains diffuse into the tissue pores and block them ( 706 ) once they solidify. Furthermore, covalent bonds ( 707 ) or other chemical bonds can be established between tissue and polymer molecules further increasing the adherence. Moreover, if a composite material containing fibers  708  is used (e.g. cellulose fibers) some of the fibers can dangle into macro- or micro-pores and once the polymer matrix around them solidifies also contribute to a higher adherence between injected material and tissue. 
         [0064]    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. 
         [0065]      FIG. 8  A liquid can only be pressurized in a contained space. In some cases such as aneurysms, when treating the surface of a vessel or a specific area such as the surface of a joint or an organ the injected liquid might flow away from the target area. Therefore this target area has to be closed. The simplest solution for this is to press the distal end onto the tissue ( FIG. 8 a   ). Contact points  801  (or contact lines) are created and the closed cavity  112  is formed where the liquid  107  can be injected. In this case the lightguide  205  is placed not directly at the distal end but slightly inside which creates a space which can be illuminated. In one embodiment especially when the tissue  301  is a hard surface such as from a tooth, the front end of the cannula consists of a soft material (e.g. rubber or any other biocompatible and soft material)  802  which deforms when pressed against the tissue. In another embodiment ( FIG. 8 b   ) the front end of the cannula has a wide opening  803 . This structure has a conic, a half-sphere or any other shape adapted to the physiology of the tissue. Such a cone can be a rigid part of the cannula. It is also imaginable that it is opened once the cannula reached its target passion for by means of a mechanical mechanism for instance similar than an umbrella or when opening a stent using a balloon. In at least one embodiment the wall of the cannula consists of a soft and highly deformable material  804  with a gas (e.g. air) or liquid (e.g. water) cavity  805  inside. In  FIG. 8 c    is an example presented where the air or liquid cavity is a ring inside the wall of the cannula which can be filled from outside using for instance a tube to access the cavity. Thus the cannula can be inserted at a minimal diameter and once it is inside its diameter can be increased. This allows to close cavity such as an aneurysm or a blood vessel to create temporarily a closed space with a given pressure. A further example is given in  FIG. 8 d   ) where only a part  806  of the otherwise rigid cannula consists of a soft material with a cavity  807  inside. Once it is pressurized the cannula is pushed in a lateral direction against the wall opposite of the tissue cavity or blood vessel.