Laser system and method for detecting and processing information - Patents.com

Abstract

To provide a laser system configured to activate a stem cell and form a hyaline cartilage tissue.SOLUTION: A laser system comprises a laser source 101, a feedback controller 106 configured to regulate a dosimetry of the laser source to produce spatially and / or temporally modulated laser light, a first optical delivery element 102 configured to guide the spatially and / or temporally modulated laser light to an area 202 in the joint to irradiate a first part 203 of the area, and a detecting element 105 configured to detect one or more physical, chemical, mechanical and / or structural characteristics in the area in a real-time.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure is in the field of medical laser technology. In particular, the present disclosure relates to a laser system that can be applied to treat joint tissue disorders in humans and animals, including osteoarthritic cartilage, bone, and ligaments. [Background technology]

[0002] Osteoarthritis (OA) is a degenerative joint disease that is a leading cause of pain and disability worldwide, affecting nearly 27 million people in the United States alone. Osteoarthritis can cause severe pain and limit mobility. Osteoarthritis refers to the progressive loss of the normal structure and function of articular cartilage, the smooth tissue that covers the moving ends of bones. Cartilage degeneration is irreversible, incurable, costly, and resistant to all known treatments. The widespread prevalence of OA has made articular cartilage repair and regeneration a major area of ​​medical research. An analysis by the U.S. Centers for Disease Control and Prevention showed that in 2003, total damage from OA and other rheumatic diseases in the United States accounted for approximately $128 billion ($80.8 billion in direct costs and $47 billion in indirect costs), equivalent to 1.2% of the U.S. gross domestic product in 2003. The total cost attributable to OA has increased significantly since 1997, and this increase is expected to continue due to an aging population and increases in obesity and physical inactivity.

[0003] Currently, the standard surgical intervention for end-stage degenerative joint disease is total joint replacement. Early surgical intervention for symptomatic cartilage lesions, including osteotomy and autologous osteochondral graft implantation, has been suggested to restore normal joint congruity and minimize further joint deterioration. However, these techniques often do not provide a long-term clinical solution, prompting the development of regenerative medicine and tissue engineering approaches to repair articular cartilage. Other strategies include cell-based (with or without scaffolds) or whole-tissue transplantation techniques. While current surgical procedures for cartilage repair are clinically useful, they fail to restore normal joint surfaces and often result in the growth of poor-quality fibrocartilage. Repair of hyaline cartilage remains an unsolved problem.

[0004] Because osteoarthritis affects various parts or tissues of the joint, such as the cartilage plate, ligaments, meniscus, periosteum, bone, and facet joints, curing multiple joint problems is extremely difficult. Other challenges facing known methods include incomplete repair with each surgery, long healing times, and the need for additional research to optimize dosimetry for different types of joints, specific combinations of OA disease, or different patients. Known methods typically require multiple surgical sessions or surgical sessions with multiple steps because they have limited healing effects during each surgery.

[0005] Cartilage is well known to have poor self-repair capabilities due to (1) the paucity of cells (chondrocytes) capable of forming new cartilage matrix and (2) the avascular nature of cartilage, which means that cellular nutrients are transported by the diffusion of water through naturally occurring pores. These natural pores become blocked with aging and disease, and the cells lacking nutrients become inactive or die.

[0006] The most common pathological feature of post-traumatic OA is articular cartilage plate lesions. When these lesions are relatively large (greater than 4 mm in size) and superficial (partial-thickness defects that do not reach the bone), they do not heal without external intervention. Lesions up to 1 cm in size can be treated by known laser treatment methods. However, prior art laser systems, particularly those mounted on endoscopes with needles that penetrate tissue to deliver laser light to the defect area, only have a small, localized effective area and cannot treat medium or large defects.

[0007] Another problem associated with conventional laser treatment is overheating of the tissue during laser irradiation, which causes tissue degeneration, death of most cells, and inflammation, which leads to the formation of fibrous tissue and the need for antibiotics.

[0008] On the other hand, stem cell-impregnated grafts are often used for large lesions. One of the problems associated with large grafts is the mismatched stress at the interface between the graft and the native cartilage. This inappropriate stress can result in poor or prolonged graft survival.

[0009] Stem cells are also used to treat joints. However, one of the biggest problems that arises in such treatments is that stem cell transplantation often results in the formation of coarse fibrocartilage with insufficient and inappropriate mechanical properties.

[0010] The prior art and knowledge is summarized in the following patents and publications: US Patent No. 10,913,943 discloses the application of a pulsed laser source to activate stem cells.

[0011] EP 1 665 997 discloses a method for generating spatially and temporally modulated laser light.

[0012] Sobol, Emil N. et al., "Laser-induced regeneration of cartilage," Journal of Biomedical Optics 16.8 (2011):080902, describes multiple mechanisms for laser-induced regeneration of cartilage within joints.

[0013] Sobol, Emil et al., "Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing," Journal of biomedical optics 22.9 (2017):091515, discloses the formation of laser-induced micropore structures on defective cartilage tissue. [Prior art documents] [Patent documents]

[0014] [Patent Document 1] U.S. Patent No. 10,913,943 [Patent Document 2] European Patent No. 1665997 [Non-patent literature]

[0015] [Non-Patent Document 1] Sobol, Emil N. et al. “Laser-induced regeneration of cartilage” Journal of Biomedical Optics 16.8(2011):080902 [Non-patent document 2] Sobol, Emil et al. “Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing” Journal of biomedical optics 22.9(2017):091515 Summary of the Invention

[0016] It is an object of the present disclosure to provide an apparatus and method that overcomes one or more of the above-mentioned problems of the prior art. The present disclosure is defined by the appended claims.

[0017] A first aspect of the present disclosure provides a laser system suitable for treating cartilage tissue within a joint, comprising: a laser source; a feedback controller configured to adjust dosimetry of the laser source to generate spatially and / or temporally modulated laser light; a first light delivery element configured to direct the spatially and / or temporally modulated laser light to a region within the joint and irradiate a first portion of the region; and a detection element configured to detect one or more physical, chemical, mechanical and / or structural properties within the region in real time, wherein the feedback controller is configured to adjust dosimetry of the laser source in real time based on real-time detected information regarding the one or more physical, chemical, mechanical and / or structural properties within the region for controlled activation of first stem cells outside the first portion of the region to form hyaline cartilage tissue.

[0018] In the context of the first aspect, the cartilage tissue can be a cartilage tissue or a part of cartilage tissue that needs treatment, i.e., a cartilage tissue lesion. The cartilage tissue lesion can show reduced functionality compared to healthy cartilage tissue or compared to newly formed hyaline cartilage tissue. The cartilage tissue lesion can also refer to a cartilage tissue or a part of cartilage tissue that does not have reduced functionality but needs to be modified to improve the quality of treatment.

[0019] The present disclosure presents a powerful concept that states that the maximum healing effect of laser treatment or each laser treatment session can be achieved by activating distant primary stem cells into directed differentiation to form hyaline cartilage tissue by localized temporally and spatially modulated laser light.

[0020] In some embodiments, the localized laser light has a wavelength of 0.01 to 10 mm3 , especially 0.1 to 1 mm 3 The laser beam can be absorbed in a tissue area of ​​a volume of 1000 nm. A small irradiated area can reduce tissue damage from direct laser irradiation and facilitate more energy-efficient and controllable modulation of the laser light. In some examples, the direct irradiated area according to the present disclosure can be small, yet a large area can be treated by laser-induced effects.

[0021] Stem cells can be activated for directed differentiation by two mechanisms: a) by subjecting the stem cells to specific stress, electrical and / or temperature conditions, and b) by introducing specific signaling molecules into the stem cells. Thus, remote control of the first stem cells can be achieved in at least two ways: (1) Direct, controlled thermomechanical activation of primary stem cells by stress waves (waves resulting from the oscillating thermomechanical properties of the medium) generated by nonuniform heating waves resulting from laser-induced coordinated rotational vibration of water dipoles in the cartilage matrix. The stress waves propagate to the primary stem cells and activate them by creating specific thermal and / or mechanical conditions for the primary stem cells. The stress waves can also drive charge distribution on the surface of, for example, gas bubbles to achieve the desired electrical conditions for directed activation. Controlled bubble generation can be induced by modulated laser light. The gas bubbles can also facilitate the generation of stress waves.

[0022] (2) Remote control of the first stem cell as indirect biochemical activation of the first stem cell by signaling molecules produced by a second cell in the first part of the region. The production of signaling molecules can be induced by modulated laser light by creating specific thermal and / or mechanical conditions for the second cell. The second cell can be a transplanted stem cell or a cell already present in the region. Examples of such signaling molecules include TGF-β, BMP, IGF, FGF, SOX, and one of the molecular chaperone families (Hsp60, Hsp70, Hsp90). The signaling molecule can be prepared separately rather than in vivo. For example, the second cell can be irradiated in vitro and then injected into the joint region. In this case, laser light does not need to be used to activate the second cell in vivo, but only to treat the region to promote the transport of the signaling molecule. Both activation methods can be achieved by real-time modulated laser light based on real-time detection information about one or more properties within the region. In particular, the one or more properties may include physical, chemical, mechanical and / or structural properties within the region.

[0023] The physician or practitioner may manually introduce a first light-delivering element near the area. The physician or practitioner may then select a function of the laser system, for example, to perform direct thermomechanical activation or indirect biochemical activation, and begin laser treatment. After laser treatment begins, it may be automatically performed until the detected information reaches a predetermined threshold, for example, when the stress or temperature of the area reaches a predetermined value. When such a threshold is reached, the laser system may stop or pause the laser treatment and await the physician's or practitioner's next instruction.

[0024] In the context of the present disclosure, "real-time" may generally refer to the timescale over which one or more physical, chemical, mechanical and / or structural properties of an intra-articular region are detected and subsequently processed, the timescale being short enough to allow for intentional adjustment of the dosimetry of the laser source via feedback based on the detected and processed information during the ongoing treatment of cartilage tissue, and in particular, during the ongoing controlled activation of stem cells outside a first portion of the region to form hyaline cartilage tissue.

[0025] In the context of the present disclosure, "real-time" may refer to a time scale of less than a few minutes. For example, detecting in real time may refer to detecting continuously over a period of minutes, or detecting minutes after an external effect to evaluate such effect. Real-time processing may refer to processing in which a result can be calculated minutes after the start of the calculation. Nevertheless, smaller time scales are possible as well.

[0026] In particular, real time may refer to a time scale of less than 20 minutes, in particular less than 10 minutes or less than 3 minutes or less than 1 minute or less than 30 seconds or less than 10 seconds or less than 1 second.

[0027] In the context of this disclosure, "adjusting the dosimetry of a laser" or "adjusting a laser" may refer to adjusting the laser during operation. However, they may also include selecting appropriate initial parameters of the laser for initiating laser treatment. In this case, detecting in real time may refer to a situation in which the characteristics are detected within a time span of up to several minutes before the laser begins to function. The laser may start with different initial conditions depending on the exact condition of the joint being treated.

[0028] In an implementation of the laser system of the first aspect, the laser can be tuned by adjusting at least one of the following laser parameters: laser pulse repetition rate, pulse sequence frequency, laser pulse duration, shape of the laser signal in the time domain, shape of the laser signal in the frequency domain, laser wavelength, pulse energy, intensity of the laser signal, number of pulses in the pulse sequence, interval duration between sequences, number of total sequences, spatial distribution of laser irradiation intensity, dimensions of the irradiated area, distance between adjacent irradiated regions, and distance shift due to propagation within the first light delivering element.

[0029] Adjusting one or more of these parameters can facilitate fine tuning based on environmental characteristics, which can enhance the precision and range of laser light modulation.

[0030] The real-time adjustment of the dosimetry of the laser source may correspond to a constant adjustment of the laser dosimetry, an adjustment of the laser dosimetry upon receiving a signal from a feedback controller, or an update of the laser dosimetry after a certain number of pulses in the sequence. The real-time adjustment may further include ceasing irradiation when real-time detected information regarding the property in the region reaches a predetermined or calculated threshold.

[0031] In a further implementation of the laser system of the first aspect, the detection element may comprise at least one of the following: an X-ray device, a CT device, an ultrasound diagnostic device (US), an MRI device, an OCT device, a (multispectral) photoacoustic tomography device (MSOT), a fluorescence molecular tomography device (FMT), an acoustic tomography device.

[0032] These types of sensing elements can provide high-resolution monitoring of an area or local environment, but can generate large amounts of data. By combining multiple different types of sensing elements with a powerful (on-board or external) computer, such as a quantum computer, the present disclosure can facilitate precise real-time control of laser modulation.

[0033] In further implementations of the laser system of the first aspect, the properties may include one or more of the following: Young's modulus of the object, speed of sound within the object, temperature of the object and / or environment, location of the object, composition of the object, dimensions of the lesion, thickness of the cartilage plate, multiple and dimensional structural defects, shape of the graft, dimensions of collagen fibrils, type of collagen within the object, amount of proteoglycan within the cartilage, stress distribution on the object, light scattering induced by the object, electrical conductivity of the object, properties related to the porous structure, and / or zones of degenerated tissue on the object such as porosity of the porous structure.

[0034] The properties may be properties of one or more objects inside the first portion of the region for reflecting the primary effect of the laser light and / or for calculating the desired conditions for generating stress waves induced by the laser light or for calculating the desired conditions for stimulating the second cell to release signaling molecules. These properties may be properties of one or more objects outside the first portion of the region for reflecting the secondary effect of the laser light and / or for calculating the desired propagation of stress waves induced by the laser light or the desired transport of signaling molecules. The properties may be properties of one or more objects positioned to be reflected by the remote first stem cell and / or for calculating the final effect of the laser light-induced remote control effect on the remote stem cell.

[0035] In an embodiment, due to the complexity of both direct thermomechanical activation and indirect biochemical activation schemes, as well as the complex environment within the human body, the desired results may be achieved by simultaneously adjusting multiple dosimetry parameters of the laser source based on calculation of real-time detected information regarding multiple characteristics of the region by specially designed algorithms.

[0036] Due to the large number of input and output parameters of the algorithm, a large feedback lag can lead to deviations from the desired effect. Real-time control can be achieved by high-performance computing capabilities. In embodiments, such computers can be (remote) high-performance computers, (remote) hybrid quantum-classical computing facilities, and / or (remote) quantum computers.

[0037] In a further implementation of the laser system of the first aspect, the feedback controller may be configured to adjust the dosimetry of the laser source such that the generated modulated laser light changes the temperature and / or stress of tissue in the first portion of the region in a particular sequence and / or simultaneously.

[0038] In a further implementation of the laser system of the first aspect, the feedback controller may be configured to adjust the dosimetry of the laser source such that the generated modulated laser light changes the temperature and / or stress field, in particular the temperature and / or stress distribution, of the first portion of the region in a specific sequence and / or simultaneously.

[0039] In direct thermomechanical activation, varying the temperature and / or stress of the tissue in the first portion of the region in a specific sequence can facilitate the generation of desired stress waves. The stress waves can be a superposition of different thermomechanical waves, allowing the temperature and / or stress of the tissue to be changed simultaneously. In indirect biochemical activation, varying the temperature and stress of the tissue in the first portion of the region in a specific sequence and / or simultaneously can facilitate the creation of desired temperature and stress conditions that stimulate stem cells in the first portion of the region to produce signaling molecules. Varying the temperature and / or stress of the tissue in the first portion of the region in a specific sequence and / or simultaneously can also facilitate the controlled formation of porous structures.

[0040] In a further implementation of the laser system of the first aspect, the system may include a channel element configured to form an access channel to an area within the joint.

[0041] In a further implementation of the laser system, the channel element is configured to deliver stem cells to the region to be activated.

[0042] In a further implementation of the laser system, the channel element is configured to deliver pre-activated stem cells to the region.

[0043] In a further implementation of the laser system, the first light delivering element is configured to direct spatially and / or temporally modulated laser light through the channel element to a first portion of the region.

[0044] Activated stem cells can be introduced from the outside. These stem cells can be introduced into the desired location of an osteoarthritic joint for cartilage tissue repair. The channel element can include the same lumen for stem cell introduction and laser light induction. For example, the first light delivery element can be inserted through the lumen before or after the stem cells are introduced through the lumen. Using the same channel element, particularly through the same lumen for stem cell introduction and laser light induction, minimizes trauma caused by access channel formation.

[0045] In embodiments, the amount, density and / or other dosimetry of stem cells (eg, dispersed in a biological fluid) can be controlled by a feedback controller in real time based on real-time sensing information.

[0046] In a further implementation of the laser system of the first aspect, the feedback controller may be configured to control the position of the first light delivering element within the area being irradiated in real time based on the real-time detected information.

[0047] For example, the feedback controller may be configured to control the first light delivering element to direct laser light to a second portion of the region that is different from the first portion of the region in real time based on real-time detected information regarding one or more physical, chemical, mechanical and / or structural properties within the region.

[0048] The first light-delivering element may comprise a single or bundle of optical fibers. The first light-delivering element may comprise multiple outcoupling elements. Changing the irradiated portion of the region may involve switching between different outcoupling elements and / or controlling individual outcoupling elements, such as tilting the angle of the outcoupling elements. The first light-delivering element may comprise a servo element configured to change the physical position of the light-delivering element to change the irradiated portion of the region. The irradiated portion of the region may be changed after activation of a remote stem cell to activate another remote stem cell. Changing the irradiated portion of the region may also be performed while activating the same remote stem cell. In the latter case, changing the irradiated portion of the region as part of the spatial modulation of the laser light may promote the generation of desired stress waves or the production of desired signaling molecules.

[0049] In a further implementation of the system of the first aspect, the feedback controller may be configured to adjust the dosimetry of the laser source based on the real-time detection information for controlled formation of a porous structure on cartilage tissue and / or another object in the region.

[0050] In the context of this disclosure, a porous structure may refer to a structure with multiple distributed structural defects. The pores of such a porous structure do not necessarily have to be rounded in the conventional sense; they may be crevices, microcavities, displacements, or other forms of structural defects that facilitate the movement of fluids and signal molecules through the tissue matrix. Furthermore, porous structures should also be distinguished from aggregates of macroscopic defects that impair the mechanical properties of tissue. In a typical configuration, a porous structure may be a microporous structure, i.e., the structural defects may have a size of less than 5 micrometers. In the early stages of the formation of such microporous structures, the formation may only alter the physical and chemical properties of the affected area, but may not significantly change the macroscopic appearance and mechanical properties of the tissue.

[0051] A microporous structure can be formed on the cartilage tissue in the region in a controlled manner, and in an embodiment, this microporous structure is formed prior to laser-induced activation of the distant stem cells.

[0052] In some embodiments, the tissue and / or object in which the porous structure is formed may already be porous prior to laser-induced porosity formation. In these embodiments, the porous structure refers to a structure that is more porous than the untreated tissue or object. In some embodiments, the formation of the porous structure may refer to an increase in porosity and / or an increase in pore size. This allows for control over the conditions that define the mechanical properties of the tissue and object, particularly their tensile strength, stress wave propagation, and other elastic and plastic properties. In another embodiment, the formation of the porous structure may refer to the unclog of an existing clogged porous structure. Because clogging can often occur in unstable porous structures, the controlled porous structure formation according to the present disclosure may be applied to unclog clogged, unstable porous structures and form stabilized porous structures for long-term stability.

[0053] Due to direct thermomechanical activation, stress waves can propagate through the cartilage tissue from the irradiated portion of the intra-articular region to stem cells on the surface of the cartilage tissue outside the irradiated first portion of the region. Creating a porous structure in a controlled manner can improve stress wave generation and propagation. On the one hand, the formation of a porous structure can change the porosity of the tissue, thus altering, particularly increasing, the interaction between the modulated laser light and the tissue due to the increased liquid content within the porous structure, promoting stress wave generation. On the other hand, the porous structure can change the physical properties of the cartilage tissue as a medium for stress wave propagation, particularly the speed of sound and Young's modulus. Therefore, cartilage tissue can be manipulated in this way to optimize stress wave propagation.

[0054] In indirect biochemical activation, the porous structure can provide an extra transport pathway for signaling molecules, i.e., a transport pathway through the pores, thereby facilitating the propagation of signaling molecules to distant stem cells. In both cases, it may be beneficial to use controlled porous structure formation to promote the activation of stem cells attached to cartilage tissue, forming hyaline cartilage bridges on the surface, thereby promoting improved healing. In an embodiment, the size of the pores, or the porosity of the porous structure, can be large enough to optimize the propagation of stress waves or promote the transport of signaling molecules. In another embodiment, the size of the pores can be small enough to prevent stem cell migration through the porous structure. In this way, stem cells can be effectively distributed over damaged cartilage tissue, preventing stem cell aggregation and thus expanding the area of ​​healing. In another embodiment, the size of the pores can be controlled within a specific range to maximize their stability.

[0055] The porous structure can reduce internal stress in a target object, such as the tissue being treated. In this disclosure, internal stress can refer to permanent or static stress in a target object, which differs from dynamic oscillatory stress changes in stress waves. Internal stress can be generated or detected throughout treatment, including scaffold implantation or laser irradiation, which can be an undesirable side effect. Detecting internal stress and reducing it by forming a porous structure can improve the quality of laser treatment and / or scaffold implantation. Therefore, the porous structure can be implemented at any stage of laser treatment to reduce internal stress in the joint area.

[0056] Additionally, the porous structure may further facilitate drug and nutrient transport in the cartilage tissue region, improving therapeutic efficacy. In embodiments, the channel elements may be configured to deliver drugs, nutrients, and / or other biochemicals before, during, and / or after irradiation.

[0057] Porous structures can also be formed within other objects within the joint region, such as implants, to create conditions for different biochemicals to be readily transported through the implant or other objects within the intra-articular region.

[0058] As outlined above, laser light can be used only to generate the porous structure without activating the second cells. In this example, signaling molecules can be prepared separately and introduced into the area after the porous structure has formed. In this way, activation of the second cells can be omitted, thus causing less damage to the injected stem cells.

[0059] In a further implementation of the laser system of the first aspect, the detecting element may comprise a receiving element.

[0060] In a further implementation of the laser system of the first aspect, the light receiving element may be configured to receive scattered light.

[0061] Scattered light can result from spatially and / or temporally modulated laser light. Light scattering can be sensitive to the formation of microporous structures or other defects at the microscopic level. Detecting and analyzing scattered light of different wavelengths allows for the use of Mie and Rayleigh scattering laws to determine the size distribution of pores, defects, or potential bubbles within the joint area that may be generated during the formation of porous structures or the generation of stress waves.

[0062] In a further implementation of the laser system of the first aspect, the detection element may comprise a second light delivering element.

[0063] In a further implementation of the laser system of the first aspect, the light delivering element may be configured to deliver a probe light signal for light scattering analysis.

[0064] The scattered light can also result from a probe light signal, which does not need to interact with the tissue or object to form pores or tissue alterations and can be used prior to laser operation to determine the initial conditions of the laser. This can facilitate initial conditions of the laser with little or no destructive side effects to the tissue or object or their environment.

[0065] In a further implementation of the laser system of the first aspect, the first light delivering element comprises a bundle of optical fibers and / or is configured to multiplex multiple laser outputs of the laser source into one fiber at the input of the first light delivering element.

[0066] This may increase the flexibility of the spatial modulation of the laser light and the scattered light detection described above.

[0067] In a further implementation of the laser system of the first aspect, the sensing element may comprise a conductivity sensing element.

[0068] In a further implementation of the laser system of the first aspect, the conductivity sensing element may be configured to sense the conductivity on the tissue or object.

[0069] In some embodiments, it may be beneficial to form a stabilized porous structure. This can be achieved by stable bubble generation. Spatially and / or temporally modulated laser light can generate microbubbles from gas dissolved in the liquid in the environment. These bubbles can be stabilized by positive charges on their surfaces. Therefore, conductivity information can reflect the state of bubble formation. Modulating the laser light taking this information into account can facilitate the controlled generation of stabilized bubbles, which can further facilitate the controlled formation of stabilized porous structures.

[0070] As outlined above, porous structures can have multiple different functions in laser therapy. The characteristics of the porous structure, such as the width and length of the pores, can be important parameters for optimizing other processes, such as stress wave generation, stress wave propagation, transport of signaling molecules, and / or transport of other biochemicals. Therefore, controlled formation and accurate detection of the corresponding characteristics can be important for achieving the effects of laser therapy. In particular, a real-time feedback controller can realize such controlled formation and / or real-time detection of the pores.

[0071] In a further implementation of the system of the first aspect, the first light delivery element can be configured to irradiate a first portion of the region to induce the formation of hyaline cartilage tissue crosslinks between the graft and cartilage tissue within the region.

[0072] The cartilage tissue may be or may include the lesion area before, during or after crosslinking, which may be considered to effectively form a cartilage tissue lesion, particularly cartilage tissue adjacent to or near the implant.

[0073] In such implementations, the implant may be delivered to the cartilage tissue through the channel element.

[0074] If the lesion area within the joint is large enough, it may be beneficial to introduce a graft into the lesion area and activate stem cells to induce differentiation between the cartilage tissue and the graft to form a hyaline cartilage bridge.

[0075] The interface between the implant and the cartilage tissue may be larger than the laser spot diameter, and multiple irradiation steps may be required to establish stable crosslinks between the implant and the cartilage tissue according to conventional laser treatment. According to the present disclosure, a single local irradiation can induce crosslink formation over most of the interface between the implant and the cartilage tissue. Therefore, far fewer irradiation steps are required. This can increase efficiency and reduce surgical trauma.

[0076] In a further implementation of the system of the first aspect, the sensing element may be configured to sense stress or stress distribution at or near the interface between the implant and the cartilage tissue.

[0077] In a further implementation of the system of the first aspect, the stress or stress distribution at or near the interface between the implant and the cartilage tissue may be detected before, during and / or after cross-link formation.

[0078] In a further implementation of the system of the first aspect, the feedback controller may be configured to control the laser source and the first light delivery element to form a porous structure at or near the interface between the graft and the cartilage tissue according to the detected stress or stress distribution.

[0079] In a further implementation of the system of the first aspect, the feedback controller may be configured to control the laser source and the first light delivery element to reduce stress resulting from the formation of a porous structure at or near the interface between the implant and the cartilage tissue according to the detected stress or stress distribution.

[0080] After the formation of bridges between the implant and the cartilage tissue, mismatch stress may occur at or near the interface between the implant and the cartilage tissue. The laser-induced porous structure can reduce the internal mechanical stress of a rigid object. However, uncontrolled formation of the porous structure may destroy the newly formed bridges in the hyaline cartilage tissue. Therefore, the porous structure, preferably a microporous structure, should be formed in a controlled manner. This can be achieved by utilizing the real-time laser adjustment method disclosed herein. The above-mentioned system suitable for forming a porous structure on cartilage tissue before stem cell activation can be directly used in this example. The controlled formation of the porous structure based on real-time detection information in these examples can be implemented using the same method.

[0081] In a further implementation of the laser system of the first aspect, the laser system may include an effect-producing element configured to produce a thermal, electrical, magnetic, and / or mechanical effect within the region, and a feedback controller configured to adjust the effect-producing element in real time based on the real-time detected information.

[0082] In a further implementation of the laser system of the first aspect, the effect-exerting element may exert a thermal, electrical, magnetic, and / or mechanical effect on tissue, objects, and / or fluids within the region.

[0083] The tissue may be or may include cartilage tissue and / or different tissues. In particular, the tissue may be outside the irradiated portion of the area.

[0084] The additional effect-producing element is configured to produce another chemical, thermal, electrical, magnetic, acoustic and / or mechanical effect in addition to or during laser irradiation in the area to enhance the quality of the telecommunications effect.

[0085] For example, the effect-producing element may comprise a heater. A system with a heater may facilitate better temperature control, especially when the laser intensity is low.

[0086] As another example, the effect-producing element may comprise an electric effect-producing element. The porous structure can be stabilized by an electric charge distributed on the surface of the bubbles. While it is possible to use only the laser effect to generate such an electric charge locally, the electric effect-producing element may introduce an external electric charge in the area of ​​the joint to improve the stability of the bubbles. As another example, the electric effect-producing element may be configured to generate an electric field in the area within the joint. As another example, the effect-producing element may produce a piezoelectric effect in the area of ​​the joint, for example to take advantage of the piezoelectric properties of collagen.

[0087] As another example, the effect-producing element may include a mechanical oscillator. The mechanical oscillator may be adjusted by a feedback controller in real time together with a laser source to generate stress waves for activating the first stem cells. The mechanical oscillator may be configured to generate acoustic waves, such as ultrasound. By combining mechanical and optical effects, the stress waves may be optimized and damage during stress wave generation may be reduced. As another example, the mechanical oscillator may be in physical contact with the cartilage tissue to be treated. As another example, the effect-producing element may include or be the same as a servo element. As another example, the effect-producing element may include or be the same as a guidewire.

[0088] In some examples, the feedback controller may utilize a combination of one or more effect-producing elements and a laser source as a whole, adjusting the effect-producing elements and the laser source simultaneously to achieve an optimal effect.

[0089] In a further implementation of the system of the first aspect, the feedback controller may be configured to adjust the laser source and / or the effect-producing element to activate or deactivate nerve endings on a real-time basis based on the real-time detected information.

[0090] Signaling molecules (neurotransmitters) can be synthesized in and released from nerve terminals and then bind to receptor proteins in the cell membrane of target tissues, which can be excited, inhibited, or functionally altered in some other way.

[0091] To better control the healing effect, for example, to reduce the production of undesired signaling molecules from the body or to promote the production of desired signaling molecules from the body, it may be beneficial to activate or deactivate nerve endings on demand. Possible deactivation or activation of nerve endings may include exposing the nerve endings to one or more of thermal, mechanical, electrical, and optical effects, such as those similar to the examples outlined above, so that desired temperature requirements, local stress requirements, local application requirements, or other requirements for deactivating or activating nerve endings can be achieved.

[0092] Possible activation may further include the removal or reduction of the size of the object compressing the nerve. For example, a low-temperature laser ablation method may be performed to reduce the fibrocartilage tissue compressing the nerve, and a feedback controller may adjust the laser source to form a porous structure on the fibrocartilage tissue in a controlled manner. Then, biological fluids, such as synovial fluid, in the area may flow into the pores. The increased biological fluid content in the porous structure may increase the interaction between the porous structure and the laser light. Therefore, a thermomechanical gradient may be created between the porous structure and adjacent areas not affected by the laser. This may result in the ablation of the irradiated fibrocartilage tissue. The laser dosimetry, particularly the time interval between pulses, may be adjusted in real time, for example, so that the time interval is long enough for the biological fluid to fill the porous structure and / or short enough to ensure the safety of the ablation.

[0093] In a further implementation of the system of the first aspect, the feedback controller may adjust the dosimetry of the laser source, the dosimetry of the effect-producing element, and / or the dosimetry of the biochemical introduction in real time based on a combination of real-time detection information, the dosimetry of the laser source, the dosimetry of the effect-producing element, and / or the dosimetry of the biochemical introduction.

[0094] The output of a feedback controller that adjusts a portion of the laser system can also be used as feedback information to adjust the same or a different portion of the laser system. In some examples, different biochemicals introduced into a region within a joint can change the tissue properties, particularly the optical and mechanical properties, of this region within the joint. For example, the feedback controller can determine the volume of biochemicals to be introduced into the region of the joint. The controller can then determine that the elasticity of this region may be increased after the introduction of the biochemicals, resulting in faster stress wave propagation or faster transport of signaling molecules. The feedback controller can then adjust the corresponding portion of the laser system accordingly.

[0095] In further implementations of the system of the first aspect, the feedback controller may comprise and / or be coupled to a (remote) high performance computer, a (remote) hybrid quantum-classical computing facility, and / or a (remote) quantum computer.

[0096] In a further implementation of the system of the first aspect, the feedback controller may comprise and / or be connected to a storage device that stores offline configuration tables, the configuration tables being calculated by a remote high performance computer, a remote hybrid quantum-classical computing facility, and / or a remote quantum computer.

[0097] The real-time adjustment of a laser based on feedback detection information of the laser affected area according to the present disclosure is a complex feedback optimization problem. Better assessment of the laser effect and accurate adjustment of the laser depend on a large amount of detection information, which may be enormous. Quantum algorithms or hybrid quantum algorithms, such as variational quantum eigensolvers, can be used in this context and may outperform conventional algorithms in optimizing systems with multidimensional parameters. Therefore, using high-performance and / or hybrid and / or quantum computers and / or hybrid computing capabilities can facilitate better control of the laser system.

[0098] In a further implementation of the method of the first aspect, the remote high performance computer, the remote hybrid quantum-classical computing facility, and / or the remote quantum computer may be located on a central server.

[0099] In a further implementation of the method of the first aspect, the central server is configured to coordinate the multiple laser systems.

[0100] A second aspect of the present disclosure is a method for detecting and processing information, comprising: a) detecting one or more physical, chemical, mechanical and / or structural properties within an intra-articular region; b) processing the detected information regarding the physical, chemical, mechanical and / or structural properties within the intra-articular region; and c) characterizing stress wave generation, stress wave propagation, signaling molecule production, signaling molecule transport, and / or porous structure formation within a region within the joint.

[0101] In implementations of the method of the second aspect, the one or more physical, chemical, mechanical and / or structural properties within the region may be one or more physical, chemical, mechanical and / or structural properties of tissue, objects, and / or fluids within the region.

[0102] The tissue may be or may include cartilage tissue and / or a different tissue.

[0103] In a further implementation of the method of the second aspect, the method comprises the following steps: d) facilitating interactions between objects within the illuminated portion of the region and objects outside the illuminated portion of the region.

[0104] In a further implementation of the method of the second aspect, the detected and processed information may be used to facilitate interactions.

[0105] In a further implementation of the method of the second aspect, the object within the irradiated portion of the area may be a fluid, a tissue, a graft, or a cell, such as a normal cell or a stem cell.

[0106] In a further implementation of the method of the second aspect, the object outside the irradiated portion of the area may be a cell, such as a normal cell or a stem cell.

[0107] In a further implementation of the method of the second aspect, the interaction may include or be a thermal, mechanical and / or electrical interaction propagated via stress waves.

[0108] In a further implementation of the method of the second aspect, the interaction may include or be an exchange of information between cells within the illuminated portion of the region and cells outside the illuminated portion of the region, for example molecular signaling information exchanged via signaling molecules.

[0109] In further implementations of the method of the second aspect, promoting the interaction may include direct promotion, for example by optimizing stress wave generation, stress wave propagation, signaling molecule production and / or signaling molecule transmission.

[0110] In some embodiments, facilitating interactions may include indirect facilitation, for example, by optimizing the formation of porous structures that indirectly facilitate stress wave propagation and / or signaling molecule transduction.

[0111] In a further implementation of the method of the second aspect, the exchange of information can refer to direct interaction with a first cell and indirect interaction with a second cell using the first cell. The first cell can be located in an illuminated portion of the region. The second cell can be outside the illuminated portion of the region.

[0112] In a further implementation of the method of the second aspect, the detected and processed information is used to adjust laser light in real time to facilitate exchange of information between cells within the illuminated portion of the region and cells outside the illuminated portion of the region, and the laser light is used to illuminate a portion of the region.

[0113] In a further implementation of the method of the second aspect, the cells within the irradiated portion of the area and / or the cells outside the irradiated portion of the area may be stem cells.

[0114] In a further implementation of the method of the second aspect, the method may further comprise promoting signaling molecules emitted by the laser-activated stem cells to activate other distant cells to differentiate or dedifferentiate in a desired direction.

[0115] In a further implementation of the method of the second aspect, the stress waves and / or signaling molecules may be configured to activate stem cells to form hyaline cartilage tissue.

[0116] In a further implementation of the method of the second aspect, obtaining the characteristics of stress wave generation, stress wave propagation, signaling molecule generation, signaling molecule transport, and / or porous structure formation in the region may be performed in real time during stress wave generation, signaling molecule generation, and / or porous structure formation.

[0117] This region may include a solid medium, a liquid medium, or a combination thereof for stress wave propagation and signaling molecule transport. For example, the medium for stress wave propagation and signaling molecule transport may be a defective tissue, a graft, or other target. It may also be a biological fluid in the treatment environment. It may also refer to a tissue or graft that includes a porous structure filled with biological fluid.

[0118] The characteristics of stress wave generation may include time-dependent temperature and / or stress changes in the region where the stress waves are generated.

[0119] The properties of the stress wave propagation may include time-dependent temperature and / or stress changes in the region through which the stress wave propagates. The properties of the stress wave propagation may further include the Young's modulus or the speed of sound of the medium.

[0120] The signaling molecule production characteristic may include a temperature range and / or a stress range that promotes the second cell to produce the signaling molecule.

[0121] The transport properties of signaling molecules may be related to the porous structure, for example, the shape and size of the pores in the porous structure, the channel length of the porous structure, or other properties that reflect the transport of signaling molecules in the porous structure. The properties of signaling molecule transport may further include properties related to biological fluid-assisted drift or diffusion. For example, the properties may include a thermomechanical gradient that indicates the drift of signaling molecules assisted by fluid flow. The properties may also include the temperature of the region within the joint that promotes the diffusion of signaling molecules in biological fluids.

[0122] The characteristics of the porous structure formation may include pore size, stability, quality, and / or characteristics used to evaluate the formed porous structure, or the rate of formation, stability, quality, and / or other characteristics used to evaluate the porous structure formation procedure.

[0123] In a further implementation of the method of the second aspect, stress wave generation, stress wave propagation, signaling molecule generation, signaling molecule transport, and / or porous structure formation can be induced by temporally and / or spatially modulated laser light generated by a laser source.

[0124] Different stress wave generation, stress wave propagation, signaling molecule generation, signaling molecule transport, and / or porous structure formation mechanisms may require different temperatures. The required temperature may reflect what will occur in that region, whether the desired effect will be achieved as expected, or whether potential damage may be caused. Furthermore, the same physical, chemical, mechanical, and / or structural properties may reflect different characteristics. For example, time-dependent stress distribution may reveal stress wave propagation, convey information about pore size distribution, or indicate the formation of degenerated tissue.

[0125] For example, the detected stress distribution can be mapped onto the detected temperature, which can provide a more accurate assessment of the laser irradiation effect. The combination of temperature detection and mechanical stress detection can reflect different characteristics of the joint area, facilitating an accurate assessment of the laser effect. Other physical, chemical, mechanical, and / or structural properties in the joint area can provide information for a better assessment of the characteristics of this area and the laser effect in this area.

[0126] While the present disclosure may provide an automatic feedback controlled laser system, such as the laser system according to the first aspect, it is understood that the method according to the second aspect need not involve adjustment of the laser system itself. For example, the method according to the second aspect may provide necessary information to a physician or practitioner operating the laser based on which the physician or practitioner can subsequently assess the lesion area within the joint and / or the expected laser effect in this area.

[0127] An evaluation system configured to perform the method according to the second aspect may include an indicator, such as an LED indicator bulb. In an embodiment, if the evaluation system determines that the treated tissue in the joint exhibits a large lesion area, it may instruct the physician or practitioner to perform laser treatment, for example, by displaying a green light. It may further indicate to the physician or practitioner where to perform the laser treatment, for example, by displaying corresponding information on a screen. In another embodiment, if the evaluation system determines that the detected information in the treated joint reaches a predetermined value, for example, if the stress is sufficiently small or the temperature is too high, it may instruct the physician or practitioner to stop the laser treatment, for example, by displaying a red light. The method may also provide instructions to the physician to perform other actions, for example, to change the laser dosimetry. The thresholds, predetermined values, and / or other evaluation criteria may be predetermined by the physician or practitioner based on a specific case, or may be stored in an offline setting table for the treatment, which may be calculated by a remote high-performance computer, a remote hybrid quantum-classical computing facility, and / or a remote quantum computer. The threshold, predetermined value, and / or other evaluation criteria may be predetermined based on the laser used by the physician or practitioner, which may be a laser in a laser system according to the first aspect of the present disclosure. The laser may also be a laser whose dosimetry can be manually adjusted.

[0128] In a further implementation of the method of the second aspect, processing the detection information may include generating a dosimetry value of the laser source in real time based on the detection information regarding physical, chemical, mechanical and / or structural properties within the region.

[0129] In a further implementation of the method of the second aspect, the values ​​may be generated in real time during the generation of stress waves, the generation of signaling molecules, and / or the formation of the porous structure.

[0130] In an automated laser system, such as the laser system according to the first aspect of the present disclosure, the generated laser dosimetry value may be directly used by a feedback controller to adjust the laser dosimetry without human intervention. The value may also be transmitted to a physician or practitioner, who can then use it to determine whether to manually adjust the laser dosimetry or stop laser treatment. As long as the information detection and processing can be performed in real time, e.g., within minutes, the physician or practitioner may have sufficient time to react to change the laser dosimetry in time for real-time laser effects, even if the physician or practitioner chooses to manually change the laser dosimetry. Compared to conventional monitoring and evaluation systems, an evaluation system employing the method according to the second aspect provides more useful and accurate feedback to a physician or practitioner operating a laser system for treating a joint.

[0131] In a further implementation of the method of the second aspect, detecting physical, chemical, mechanical and / or structural properties within the region may include determining a temperature or temperature field within the region, wherein dosimetry of the laser source is generated when the temperature and / or its distribution is within a predetermined range.

[0132] In a further implementation of the method of the second aspect, no dosimetry of the laser source may be generated if the temperature is not within a predetermined range.

[0133] In a further implementation of the method of the second aspect, the laser treatment may be terminated if the temperature is not within a predetermined range.

[0134] In the laser treatment according to the present disclosure, parameters can be adjusted using stress waves and signaling molecules to maintain the detected temperature within a specific range that defines the activation state of the stem cells. For example, a second cell heated by modulated laser light can be heated to 40-45°C for a few seconds, e.g., less than 20 seconds. This can activate the second cell to produce signaling molecules.

[0135] As another example, the temperature at which the stress waves are generated can be varied and controlled by modulated laser light depending on the desired reach of the stress waves and the behavior of the stress wave dissipation in the environment.

[0136] For the formation of a stabilized porous structure, the parameters can be adjusted so that the detected temperature can be maintained within a predetermined range below a temperature threshold. At lower temperatures, bubbles can be stabilized. In a typical configuration, the temperature threshold can be determined to be a value above 40°C and / or below 80°C.

[0137] For deactivation of compressed nerve endings, parameters can be adjusted so that the detected temperature can be maintained above a temperature threshold of 50°C to 90°C. This can increase the efficiency of the laser effect and reduce energy waste, thus facilitating the efficient use of resources.

[0138] For example, a monitoring system implementing the process of the second aspect may provide a doctor or practitioner with supplemental information on how to operate the laser system, processing the temperature according to the current task and / or other characteristics within the area within the joint.

[0139] In a further implementation of the method of the second aspect, processing the detected information regarding the physical, chemical, mechanical and / or structural properties within the region within the joint may further include consideration of the effect of the detected temperature on the thermodynamic parameters of the medium, in particular the nonlinearity of the thermodynamic parameters.

[0140] During laser treatment, laser light can be absorbed by the medium. Modern diagnostic techniques based on laser treatment ignore the effects of local temperature increases on the medium's thermodynamic parameters (e.g., thermal conductivity, density, thermal expansion coefficient, and isobaric specific heat capacity) due to such laser light absorption. Conventional diagnostic techniques assume that the thermodynamic parameters are constant. However, even small increases in local temperature can change the values ​​of the medium's thermodynamic parameters, and the nonlinearity of thermal parameters in the heat diffusion thermomechanical equations must be considered. The most significant changes in parameters can be attributed to structural and phase transformations that occur in tissue during laser irradiation.

[0141] In a further implementation of the method of the second aspect, the physical, chemical, mechanical and / or structural properties may comprise scattered light properties.

[0142] In a further implementation of the method of the second aspect, processing the detected information may further include calculating a pore size distribution of the porous structure based on the scattered light.

[0143] In a further implementation of the method of the second aspect, the laser may be configured to generate bubbles from gas molecules dissolved in a liquid in the environment.

[0144] This can facilitate the formation of a stabilized microporous structure, which can alter the stress on the tissue or object without destroying the tissue or object.

[0145] In a further implementation of the method of the second aspect, processing the detected information may further include calculating a stress distribution and / or a temperature distribution in the region.

[0146] In a further implementation of the method of the second aspect, processing the detected information may include analyzing a thermomechanical gradient within the region.

[0147] In a further implementation of the method of the second aspect, processing the sensed information may include mapping the stress distribution to a temperature distribution and / or evaluating a correlation between the stress distribution and the temperature distribution.

[0148] The spatially resolved distribution can provide more information about the laser effect, which can increase the accuracy of the laser adjustment.

[0149] In a further implementation of the method of the second aspect, the method may include obtaining a cross-linking profile of the tissue in real time during cross-linking.

[0150] Compared to laser treatment, hyaline formation can occur over a much longer time scale. Nevertheless, it may be possible to indirectly infer whether the state of hyaline crosslinking has been reached and / or whether crosslinking has already begun by manipulating the physical, chemical, mechanical, and / or structural properties of tissue in the area within the joint. This can be inferred by slight changes in the physical, chemical, mechanical, and / or structural properties of the area of ​​the joint compared to the same properties before activation.

[0151] In a further implementation of the method of the second aspect, the method may include detecting a stress distribution at or near the interface between the cartilage tissue and the implant.

[0152] The cartilage tissue may be or may include the lesion area before, during or after crosslinking, which may be considered to effectively form a cartilage tissue lesion, particularly cartilage tissue adjacent to or near the implant.

[0153] In a further implementation of the method of the second aspect, the detected stress distribution may be used to vary the stress at or near the interface between the cartilage tissue and the implant.

[0154] In a further implementation of the method of the second aspect, the method may further comprise determining a location at or near the interface between the cartilage tissue and the implant where the stress reaches a predetermined value.

[0155] This location may correspond to an area that needs to be treated or a location where there is residual stress. For example, laser radiation can be used to create a porous structure to reduce the stress at this location.

[0156] Inspecting the residual stress at or near the interface between the implant and cartilage tissue and alleviating it, for example by laser treatment, may reduce the likelihood of apoptosis of cells within the tissue and facilitate implant implantation, which may effectively increase the power per actuation of the laser radiation, optimizing resource use.

[0157] In further implementations of the method of the second aspect, processing the detection information may be performed in a high performance computer (on-board or remote), a hybrid quantum-classical computing facility (on-board or remote), and / or a quantum computer (on-board or remote).

[0158] In further implementations of the method of the second aspect, the method of the second aspect may be encompassed in an algorithm designed for a high performance computer, a hybrid quantum-classical computing facility, and / or a quantum computer.

[0159] In a further implementation of the method of the second aspect, the remote high performance computer, the remote hybrid quantum-classical computing facility, and / or the remote quantum computer may be located on a central server.

[0160] In a further implementation of the method of the second aspect, the central server is configured to coordinate the multiple laser systems.

[0161] A third aspect of the present disclosure is a method for treating a joint using temporally and / or spatially modulated laser light comprising a treatment step, a) detecting one or more physical, chemical, mechanical and / or structural properties within a region within the joint and feeding back detected information regarding the physical, chemical, mechanical and / or structural properties to a feedback controller in real time; b) modulating in real time by a feedback controller, based on the real-time detection information, the laser light irradiating the first portion of the region, wherein the first stem cells outside the first portion of the region are suitable for activating and forming hyaline cartilage tissue.

[0162] In implementations of the method of the third aspect, porous structures may be formed in tissues and / or implants.

[0163] In implementations of the method of the third aspect, the porous structure may be formed with controlled length and / or width of the pores.

[0164] In a further implementation of the method of the third aspect, the first stem cells may be introduced into an intra-articular area.

[0165] In a further implementation of the method of the third aspect, the porous structure may be formed to reduce mismatch stress between the cell-laden scaffold and the native tissue in the region.

[0166] In a further implementation of the method of the third aspect, second cells in the first portion of the region of the joint may be activated to produce a signaling molecule, the signaling molecule configured to activate the first stem cell.

[0167] In a further implementation of the method of the third aspect, stress waves are induced via modulated laser light to activate the first stem cells.

[0168] In a further implementation of the method of the third aspect, the method is performed on a high performance computer (on-chip or remote), a hybrid quantum-classical computing facility (on-chip or remote), and / or a quantum computer (on-chip or remote). [Brief explanation of the drawings]

[0169] In order to more clearly describe the technical features of the embodiments of the present disclosure, the accompanying drawings illustrating the embodiments are briefly introduced in the following description. The accompanying drawings in the following description are only some embodiments of the present disclosure, and modifications of these embodiments are possible without departing from the scope of the present disclosure defined in the claims. [Figure 1] 1 is a schematic diagram of a laser system according to an embodiment. [Figure 2] 1 is a schematic diagram of a laser system according to an embodiment. [Figure 3] 1 is a flowchart illustrating a method for detecting and processing information according to an embodiment. [Figure 4] 1 is a flowchart illustrating a method of treating a joint according to an embodiment. [Figure 5a] 1 is a structured illumination microscopy (SIM) image of intact cartilage from a minipig joint before laser treatment. [Figure 5b] Structure illumination microscopy (SIM) image of cartilage from a minipig articular cartilage after laser treatment, showing a porous structure with pores of 3-10 μm. [Figure 5c] Structured illumination microscopy (SIM) image of cartilage from a miniature pig articular cartilage after laser treatment showing a porous structure with 3-15 μm pores whose surfaces are covered by calcium ions. [Figure 5d] Structured illumination microscopy (SIM) image of cartilage from a minipig articular cartilage after laser treatment showing 1-2 μm bubbles whose surfaces are covered by calcium ions (white ring). [Figure 6] The optical fiber has a diameter of 400 μm and is a microscopic image showing the formation of bubbles in cartilage tissue under the action of laser irradiation. [Figure 7] 1 is a graphical representation of the calculated kinetics of porous structure formation in laser-treated cartilage plates of equine joints. [Figure 8a] 1 is a histological image of minipig articular cartilage in an untreated joint 52 days after laser treatment, showing the non-repairing lesion. [Figure 8b] 1 is a histology image of miniature pig articular cartilage in a treated joint 52 days after laser treatment showing restoration of cartilage plate thickness. [Figure 8c] 10 is a histological image of miniature pig articular cartilage in a treated joint 52 days after laser treatment showing new chondrocytes with multicellular clones and regenerated splenic lamina. [Figure 8d] 1 is a histology of miniature pig articular cartilage in a treated joint 52 days after laser treatment, showing areas of diseased chondrocytes. [Figure 8e] 1 is a histological image of miniature pig articular cartilage in a treated joint 52 days after laser treatment, showing chondrocyte regeneration by multicellular clones. [Figure 8f] 1 is a histology of miniature pig articular cartilage in a treated joint 52 days after laser treatment, showing the formation of hyaline fibrocartilage. [Figure 9a] Electron micrograph of normal miniature pig articular cartilage showing thin fibrils 15-35 nm in diameter and an interregional matrix consisting of granular material of proteoglycan. [Figure 9b] Electron micrograph of regenerated miniature pig cartilage 52 days after treatment showing small interregional matrices containing numerous collagen fibrils and long central collagen fibrils. DETAILED DESCRIPTION OF THE INVENTION

[0170] The following description provides examples of implementation of the present disclosure and the scope of the present disclosure, but the present disclosure is not limited to the provided examples. Any modifications or substitutions can be easily made by those skilled in the art. Therefore, the scope of protection of the present disclosure is defined by the appended claims.

[0171] Stem cells are crucial for the regeneration and restoration of living tissues. Stem cells are pluripotent cells that can differentiate into different specific cells in the human body and restore degenerated tissues and organs. All cells in living tissues require nutrition and respiration, which are provided by blood, but in avascular tissues such as the cartilage of joints and spine or the cornea of ​​the eye, nutrients and oxygen are provided by water transport through a natural micropore system. In diseased tissues, this micropore system is blocked, and cells without nutrients gradually become dormant and then die.

[0172] Transplantation of exogenous stem cells or specific cells can bring about some improvement, but this improvement is always temporary and the recovery is incomplete because it does not solve the problems of (i) adequate nutrition and (ii) control of the direction of stem cell differentiation.

[0173] The process of stem cell differentiation is governed by signaling molecules released by existing cells and the environment, such as surrounding tissues. However, diseased tissue lacks signaling molecules, and degenerated tissue cannot promote the correct direction of cell differentiation. This is why the infusion of stem cells into damaged and degenerated cartilage in intervertebral discs and joints can only be beneficial for acute injuries, but it is not effective for chronic osteoarthritis, where fibrous tissue usually grows instead of hyaline cartilage with sufficient mechanical properties.

[0174] Therefore, stem cell applications in medicine require (i) waking up sleeping cells, (ii) controlling their precise differentiation, and (iii) providing an adequate and permanent supply of them. The use of lasers makes it possible to address all three of these challenges.

[0175] Laser systems according to the present disclosure may be used for: (1) Induction of stress waves.

[0176] It is known that most cells are sensitive to external mechanical loads of specific frequencies and amplitudes. Specific modulation of a laser source to generate spatially and / or temporally modulated laser radiation can generate localized thermal and mechanical vibrations that propagate through the medium and generate the desired mechanical load and / or temperature conditions in which distant stem cells are located. This controls the correct directional differentiation of distant stem cells.

[0177] Modulated laser light can also control the dedifferentiation of mature chondrocytes and other cells, allowing tissue cell populations to be reactivated toward regaining their ability to divide and restore lost tissue volume.

[0178] (2) Induction of signaling molecules.

[0179] Spatially and temporally modulated laser radiation can act locally and intensively on cells that provide specific signaling molecules, shock proteins, to awaken other dormant cells. Thus, laser irradiation allows for the activation of cells by affecting even a small fraction of existing cells without damaging and degenerating the remaining cells and the intercellular matrix.

[0180] (3) Controlled formation of porous structures and induction of growth behavior.

[0181] The total number of activated cells is determined by the propagation distance of the signaling molecules and the stress waves. The propagation distance depends on the permeability of the tissue matrix and the speed of sound within the matrix, which can be significantly improved by laser-induced porous structure formation. Therefore, laser-induced porous structure formation is an important factor in the positive effects of laser treatment.

[0182] (4) Controlled formation of porous structures and induction of internal stress relaxation.

[0183] Internal stresses in tissues or implants or their interfaces can be harmful to cells within the matrix. Long-term unrelieved internal stresses can lead to cell death. Laser-induced porous structure formation can relieve such stresses.

[0184] (5) Stabilization of laser-induced porous structures.

[0185] The laser radiation according to the present disclosure also provides long-term durability of positive effects, particularly by stabilizing the porous structure created by the distributed charge on the surface of the bubbles generated by the laser light. This mechanism allows for stabilization of the porous structure created under the modulated laser radiation generated by the laser source. The stabilized porous structure reliably facilitates signaling molecule / drug / nutrient transport.

[0186] (6) Thermal control of laser light.

[0187] Overtreatment, especially overheating of tissue, can result in loss of stability or tissue degeneration instead of tissue repair. Therefore, thermal control of laser light based on real-time detection information can avoid laser overheating or overtreatment.

[0188] All of the above positive effects of laser therapy can be achieved in a specific range of dosimetry and real-time adjustment of the laser source.

[0189] Thus, laser activation of stem cells provides:

[0190] (i) A direct thermomechanical effect on existing cells that activates their proliferation and synthetic activity.

[0191] (ii) Mediated by specific shock proteins (signaling molecules) released by laser-affected cells.

[0192] (iii) The creation of conditions for the rapid proliferation of nutrient and signaling molecules over considerable distances beyond the area of ​​direct laser exposure, resulting in the activation of numerous cells and their coordinated regenerative activity, resulting in the rapid regeneration and growth of tissues of given composition and properties, e.g., the regeneration of hyaline cartilage in osteoarthritic joints.

[0193] Degenerated cartilage contains few natural stem cells. Therefore, it usually takes 3 to 6 months after laser surgery for pain relief and for patients to return to normal activities. The combination of stem cell transplantation and laser irradiation using the new laser system significantly shortens postoperative recovery time and makes recovery more complete. Furthermore, any ordinary orthopedic surgeon can use this automated feedback laser system to treat osteoarthritis of the joint after approximately 2 to 3 days of training.

[0194] Typical System 1 is a schematic diagram of a laser system disclosed by the present disclosure. The laser system is suitable for treating cartilage tissue within a joint 201. The laser system includes a laser source 101, a feedback controller 106 configured to adjust the dosimetry of the laser source 101 to generate spatially and / or temporally modulated laser light, a first light delivery element 102 configured to direct the spatially and / or temporally modulated laser light to a region 202 within the joint 201 to irradiate a first portion 203 of the region 202, and a detection element 105 configured to detect one or more physical, chemical, mechanical, and / or structural properties within the region 202 in real time, wherein the feedback controller 106 is configured to adjust the dosimetry of the laser source 101 in real time based on real-time detected information regarding the one or more physical, chemical, mechanical, and / or structural properties within the region 202 for controlled activation of first stem cells 204 outside the first portion 203 of the region 202 to form hyaline cartilage tissue.

[0195] FIG. 2 is a schematic diagram of a laser system according to an embodiment.

[0196] The laser system may include a diagnostic element 106a configured to receive and process the detected information. The diagnostic element 106a includes a user interface configured to present the detected information to a user, such as a researcher or physician. For example, the user interface may be configured to present stress and temperature distributions within the region 202. The diagnostic element 106a may transmit the raw detected information to a remote high-performance computer, a remote hybrid computing facility, and / or a remote quantum computer 106d. The diagnostic element 106a may further be configured to preprocess the detected information. For example, the diagnostic element 106a may be configured to analyze the detected information regarding scattered light and determine the size distribution of pores within the porous structure.

[0197] The laser system may further comprise a feedback control element 106b configured to manage data flow within the laser system. The data flow may include a flow of real-time detected information regarding one or more physical, chemical, mechanical, and / or structural properties within the region 202, a flow of processed / preprocessed detected information, and generated commands to adjust the dosimetry of the laser source 101. The feedback control element 106b may be configured to control the direction and sequence of the data flow such that the irradiation of the laser source 101 can be modulated in real time based on the real-time detected information.

[0198] The laser system may further comprise a radiation modulation element 106c configured to temporally and spatially modulate the radiation of the laser 101 source. The radiation modulation element 106c may be configured to receive commands generated to modulate the radiation of the laser 101 and adjust the dosimetry of the laser source 101, or the radiation modulation element 106c may be configured to receive dosimetry directly from an external high performance computer, a remote hybrid computing facility, and / or a remote quantum computer 106d.

[0199] The laser system may further include an external high performance computer, a remote hybrid computing facility, and / or a remote quantum computer 106d configured to process the detection information or preprocessed detection information to generate commands for modulating the radiation of the laser source 101 or adjusting the dosimetry of the laser source 101.

[0200] The external high performance computer, the remote hybrid computing facility, and / or the remote quantum computer 106d can be configured to solve equations that define thermo-mechanical problems, such as heat propagation problems, mechanical problems, such as problems related to the deformation of a medium deformation, etc. The solutions can help optimize the control of stress waves.

[0201] The external high performance computer, the remote hybrid computing facility, and / or the remote quantum computer 106d may be configured to solve equations that define chemical process problems, such as chemical bond breaking problems. The external high performance computer, the remote hybrid computing facility, and / or the remote quantum computer 106d may be configured to calculate the dynamics of pore shape and size. This solution may help optimize the controlled formation of porous structures.

[0202] The external high performance computer, remote hybrid computing facility, and / or remote quantum computer 106d can be configured to solve kinetic problems, such as equations defining the drift and diffusion of signaling molecules. The solution can help optimize the transport of signaling molecules in region 202.

[0203] An external high performance computer, a remote hybrid computing facility, and / or a remote quantum computer 106d can be configured to calculate the dynamics of tissue degeneration. This solution can be useful for controlling temperature and stress within region 202 to minimize damage.

[0204] An external high performance computer, a remote hybrid computing facility, and / or a remote quantum computer 106d may be configured to use the solution of the above inverse problem to establish optimal dosimetry for each step of the laser treatment. The calculations may be performed within a small time interval, e.g., within milliseconds to minutes, such that a method for treating a joint 201 according to the present disclosure may be performed continuously.

[0205] The diagnostic element 106a, the feedback control element 106b, the radiation modulation element 106c, and the high-performance computer, remote hybrid computing facility, and / or remote quantum computer 106d may be part of the feedback controller 106 of Figure 1. While Figure 2 shows a separation of the diagnostic element 106a, the feedback control element 106b, the radiation modulation element 106c, and the high-performance computer, remote hybrid computing facility, and / or remote quantum computer 106d, this separation should not be interpreted as a physical separation, but rather as a separation of their logical functions. The feedback controller 106 may also refer to one or more combinations of the diagnostic element 106a, the feedback control element 106b, the radiation modulation element 106c, and the high-performance computer, remote hybrid computing facility, and / or remote quantum computer 106d.

[0206] For example, if the feedback controller 106 is configured only to process detected information regarding physical, chemical, mechanical, and / or structural properties within the region 202 and obtain characteristics of stress wave generation, stress wave propagation, signaling molecule generation, signaling molecule transport, and / or porous structure formation within the region 202, the diagnostic element 106a alone, or a combination of the diagnostic element 106a with a high-performance computer, remote hybrid computing facility, and / or remote quantum computer 106d, can be considered the feedback controller 106, in which case the feedback controller 106 facilitates evaluation of stress wave generation, stress wave propagation, signaling molecule generation, signaling molecule transport, and / or porous structure formation within the region 202, as well as initialization of parameters of the laser source 101.

[0207] For example, if the feedback controller 106 is further configured to process the detection information in real time during the formation of the porous structure or the generation of stress waves / signaling molecules induced by the temporally and spatially modulated radiation of the laser source 101, the combination of the feedback control element 106b and the diagnostic element 106a can be considered as the feedback controller 106, in which case the feedback controller 106 facilitates monitoring the laser-induced porous structure formation and stem cell activation. For example, a physician can decide when to discontinue laser irradiation depending on whether the pore size distribution of the porous structure reaches a predetermined threshold.

[0208] The laser system may include a laser 101 configured to have its radiation spatially and temporally modulated by a feedback controller 106. Spatial modulation may refer to changing the location, shape, and specific intensity distribution of the laser beam and laser-irradiated area of ​​the laser, as well as the laser-induced light within the laser-irradiated area. To achieve such spatial modulation, the laser system may include one or more laser sources 101. While FIG. 2 shows only two laser sources 101, a laser system according to the present disclosure may include more laser sources 101.

[0209] The laser light delivered by the laser source 101 may be coherent or non-coherent.

[0210] Multiple lasers 101 can facilitate complex spatial modulation of laser illumination. Spatial modulation can also be achieved by combining one or more lasers with other supporting passive elements such as lenses, mirrors, optical splitters, and other optical systems. Each of the lasers 101 can implement independent temporally modulated illumination. Temporally modulated laser illumination is typically a series of pulses of laser illumination with variable pulse repetition rate, pulse duration, pulse intensity, or other variable attributes of the laser pulses. Temporally modulated laser illumination can also refer to non-pulsed laser radiation with variable shape in the time domain and variable shape in the frequency domain.

[0211] The illumination of the laser source 101 may be modulated in real time, which may include constantly adjusting the dosimetry of the laser source 101, adjusting the dosimetry upon receiving a signal from the feedback controller 106, or updating the laser dosimetry after a certain number of pulses in a sequence.

[0212] The dosimetry of the laser source 101 is adjusted based on real-time detection information. For example, the less damage to the joint, the more tissue elasticity is required. In this case, based on the real-time detection information, the feedback controller 106 can determine that a larger amplitude mechanical effect requires a shorter pulse duration, and that elastic media transfer signals at a faster rate, so a higher sequencing frequency of pulses is required. The dosimetry of the laser source 101 can then be adjusted accordingly.

[0213] In another example, the joint is more damaged. Based on the real-time detection information, the feedback controller 106 can determine that the laser pulse should be longer to induce a smaller amplitude of the mechanical effect. Furthermore, the pulse sequence frequency needs to be smaller because more time is needed to transmit the wave energy. Therefore, the number of irradiation sequences and the number of exposure zones needs to be increased.

[0214] The laser source 101 in this disclosure may be a combination of several types of lasers, including solid state lasers (eg, NdYag lasers or Holmium lasers) and / or diode lasers.

[0215] Each of the laser sources 101 may be further assigned to different tasks. For example, during treatment, the first laser source 101 may generate modulated laser light to heat or modify tissue, while the second laser source 101 may generate modulated laser light to generate stress waves. As another example, the first laser source 101 may generate modulated laser light for a photochemical or other non-thermal effect. The modulated laser light of the first laser source 101 may activate cells to promote the absorption of other wavelengths, while the second laser source may generate modulated laser light for the controlled formation of porous structures or for the redistribution of material within the nucleus pulposus of a spinal disc.

[0216] The laser system may further comprise a light delivering element 102 configured to deliver modulated laser radiation or laser light to the target. The light delivering element 102 may be an optical fiber, an optical fiber bundle, or another type of light delivering element. The light delivering element 102 may also be configured to deliver other laser signals, such as a probing laser signal for detecting specific characteristics within the joint 201. In an exemplary embodiment, the imposed laser modulation may account for possible distortions of the laser signal due to propagation within the laser delivery system 102 and implement corresponding compensation. The light delivering element 102 may comprise an optical outcoupler for delivering the laser signal to the target in the form of laser radiation.

[0217] The laser system may further include one or more detection elements 105. The detection elements 105 are configured to detect one or more physical, chemical, mechanical, and / or structural properties within the region 202 of the joint 201. The one or more physical, chemical, mechanical, and / or structural properties may include temperature, stress, pore size and number, type and dimension of structural defects, collagen type and collagen fiber diameter, thermomechanical properties, optical properties, electrical properties, and other properties that characterize the environment within the region 202 and the condition of the tissue within the region 202. The properties may be detected in direct and indirect ways. For example, the detection element 105 may include a conductivity measuring element configured to measure the electrical conductivity of the tissue. This property can then be fed back as an electrical signal. In another example, the detection element 105 may include a light receiving element configured to receive scattered light. The scattered light is fed back as an optical signal and can be processed to deliver information about temperature, stress, bubble size distribution, and size distribution of pores and other structural defects based on the characteristics of the optical signal, such as, but not limited to, wavelength distribution and angular intensity distribution. In a typical embodiment, the detection element 105 may comprise a conventional diagnostic device such as one of the following: X-ray, CT, ultrasonography (US), MRI, OCT, OCE, multispectral photoacoustic tomography (MSOT), fluorescence molecular tomography (FMT), and acoustic tomography.

[0218] The laser system may further include a channel element 103 configured to form an access channel to the treatment target region 202 within the joint 201. In an embodiment, the channel element 103 may comprise a hollow cylinder having a predetermined cross-sectional profile. The hollow cylinder may be a needle. The predetermined cross-sectional profile may be in the form of a circle or an ellipse. The hollow cylinder may be thin-walled to minimize trauma during access channel formation. The channel element 103 may be suitable for the introduction of biochemicals such as stem cells, drugs, gases, or signaling molecules.

[0219] The gaseous biochemical may be CO gas. The gaseous biochemical may be used to introduce gas bubbles into the region 202 of the joint 201. The gas bubbles may be configured to aid in the stable formation of a porous structure or the generation of stress waves.

[0220] The administration of such biochemicals or their introduction may be controlled by the feedback controller 106. The administration may include liquid and gas phase compositions and / or chemicals or biochemicals. The biochemicals may include liquid or gas phases. The administration of the biochemical introduction may include the presence or absence of fluid medium aspiration. The administration of the biochemical introduction may further include parameters such as the rate or pressure of such fluid medium aspiration.

[0221] The pressure is to administer the fluid medium. During laser treatment, the light delivery element 102 can be introduced into the region 202 of the joint 201 through the channel element 103. In an embodiment, the hollow cylinder can be 5-15 cm long and configured to perform the puncture of the joint 201. Prior to the puncture, control of the positioning of the channel element 103 is performed by the feedback controller 106.

[0222] The channel element 103 may be configured for precise positioning within the joint 201 and for recording the position of the laser light impinging on the target or the position of the detected information by the detection element 105, thereby realizing precise spatial modulation of the laser signal and obtaining the spatial distribution of the detected information. In an exemplary embodiment, the channel element 103 may further comprise and be attached to a servo element for precise position control.

[0223] The laser system may further comprise an effect-exerting element 104 configured to exert another chemical, thermal, electrical, magnetic, acoustic and / or mechanical effect in addition to or during the laser irradiation in the region to enhance the quality of the telecommunication effect of the modulated laser light. In an embodiment, the effect-exerting element 104 may be a shaft controllably movable within the channel element 103 and capable of simultaneously performing an oscillatory motion at a predetermined frequency.

[0224] Typical Method 3 is a flowchart illustrating a method for detecting and processing information according to an embodiment. In this embodiment, the method includes: a) detecting one or more physical, chemical, mechanical and / or structural properties within an intra-articular region; b) processing the detected information regarding the physical, chemical, mechanical and / or structural properties within the intra-articular region; and c) characterizing stress wave generation, stress wave propagation, signaling molecule production, signaling molecule transport, and / or porous structure formation within a region within the joint.

[0225] As outlined above, the method shown in FIG. 3 can be used to evaluate porous structure, stress distribution, signaling molecule generation, signaling molecule transport, stress wave generation, and / or stress wave propagation. This structural evaluation can be performed to initialize the laser operating state. This method can further be used to monitor and evaluate the effects of modulated laser radiation on the joint. This laser effect evaluation can be performed to control laser effects or prevent laser-induced damage in the joint.

[0226] The method shown in Figure 3 d) It may further comprise the step of promoting signaling molecules released by the laser-activated stem cells that activate other distant cells to differentiate or dedifferentiate in a desired direction.

[0227] FIG. 4 illustrates a method for treating a joint using temporally and / or spatially modulated laser light, including a treatment step: a) detecting one or more physical, chemical, mechanical and / or structural properties within a region within the joint and feeding back detected information regarding the physical, chemical, mechanical and / or structural properties to a feedback controller in real time; b) modulating in real time by a feedback controller, based on the real-time detection information, a laser light irradiating a first portion of the region within the joint, the first portion being suitable for activating first stem cells outside the first portion of the region to form hyaline cartilage tissue.

[0228] Below is presented an example of a method for treating a joint using temporally and / or spatially modulated laser light, which corresponds to the method shown in Figure 4 with additional optional steps.

[0229] In the first step of this method, the patient's skin is treated with iodine and alcohol, for example, by infiltration of anesthesia with 2% lidocaine and 0.5% novocaine solution. Next, an access channel to the joint is created. This can be performed by standard arthrocentesis using an 18G needle 5-15 cm long.

[0230] In a second step of the method, the first light-delivery element 102 is introduced into the treatment target 202 within the joint 201 and positioned as directed by the feedback controller 106 .

[0231] In a third step of the method, an initial dosimetry for the laser source 101 is selected based on real-time detection information from the detection element 105. The initial dosimetry may be determined based on a previous diagnosis or may be determined in the field.

[0232] In a fourth step of the method, the region 202 is irradiated based on the real-time detection information to form a porous structure in the region 202, eg, cartilage tissue, within the joint 201 in a controlled manner.

[0233] The formation or restoration of cartilage tissue occurs due to the formation of new porous structures and / or the cleaning and declogging of existing porous structures in the articular vitreous plate. Conventional drilling techniques for cartilage plates and adjacent bone are used to create pores tens of microns in diameter. However, these pores tend to regrow, and therefore, this effect is temporary. Laser-induced formation of smaller pores of micron and submicron sizes makes this effect permanent due to the stabilization of the small pores by calcium ions. Figure 5a shows a structured illumination microscopy (SIM) image of unirradiated cartilage. Pores in laser-treated cartilage tissue are shown in Figures 5b-5d. SIM images of cartilage from a miniature pig articular cartilage after laser treatment show a porous structure with pores of 3-10 μm in size in Figure 5b. Under natural mechanical load, fluid is forced out of the cartilage plate, while cations, calcium and sodium, leave the cartilage. Sodium ions migrate faster, while potassium remains and accumulates on the surface of the pores. The repulsion of calcium ions within the small pores prevents their contraction and stabilizes the pores. A laser-induced pore 3 μm wide and 15 μm long with its surface covered by calcium ions is shown in Figure 5c.

[0234] A stable bubble of 1–2 μm size whose surface is covered by calcium ions (white ring) is shown in Figure 5 d.

[0235] In a fifth step of the method, biochemicals are introduced into region 202. The biochemicals may include therapeutic stem cells or drugs. The stem cells may be irradiated with a laser system prior to their introduction into region 202 of joint 201, so that signaling molecules are already produced prior to their introduction into region 202 of joint 201.

[0236] In particular, biochemicals may further include biochemicals that affect metabolic processes in cartilage tissue, biochemicals that modulate the cellular response of cartilage tissue to external effects, biochemicals that affect the histological components of other types of tissues such as nerve, vascular tissue, etc., biochemicals that intentionally modify the physical and / or chemical properties of cartilage tissue, and / or biochemicals that have a combined effect on both the biological processes within the tissue and its physical or chemical properties.

[0237] Examples of such biochemicals may include corticosteroids and analogs thereof, such as dexamethasone, vitamins or vitamin-like preparations, such as vitamin C, enzymes or antienzymes, amino acids, macrophages or their chemical precursors, glucose, antioxidants, vitreous or another biostimulant, and / or calcium preparations.

[0238] Biochemicals may include, in particular, signaling molecules, such as growth factors and cytokines, that stimulate repair processes in cartilage tissue, as well as corresponding expression inducers and / or synthesis of one or more growth factors or cytokines. Examples of such growth factors or cytokines include TGF-β, pDGF, IGF-1, FGF, EGF, OP-1, BMP-2, and BMP-12. These types of biochemicals can be obtained by culturing chondrocytes. These types of biochemicals can increase the production of proteoglycans and type II collagen, enhance the expression of aggrecan mRNA, induce cell proliferation, and inhibit their apoptotic death. They can further promote regenerative modifications in cartilage tissue, such as an increase in proteoglycan content and the appearance of cell clusters similar to those in normal hyaline cartilage.

[0239] Biochemicals may further include blockers or competitors of receptors for growth factors and cytokines that have anti-inflammatory effects, as well as biochemicals that suppress or inhibit the synthesis of certain classes of receptors.

[0240] The biochemicals may further include substances that affect the ion permeability of the outer and inner membranes of chondrocytes, such as blockers or activators of ion channels.

[0241] The biochemicals may further include heat-labile precursors of biologically active substances, such as small amounts of metalloproteinases, provided that the tissue temperature does not exceed 38°C.

[0242] The biochemical may further include a photosensitizer or a bioactive agent coupled to a photosensitizer.

[0243] The biochemical material may further include a first stem cell or a stem cell extract. The biochemical material may further include a composite of substitute cartilage tissue prepared using tissue engineering methods, the composite consisting of stem cells or chondrogenic cells. The composite may be cultured in vitro on a special matrix support, such as an artificial tissue substitute, provided that the structural and functional properties of such a tissue construct are preserved when passing through the channel element 103.

[0244] The biochemicals may include drugs that have an effect on nerve endings or local anesthetics. The biochemicals may further include drugs that have an effect on granulation tissue blood vessels that grow into cartilage defects under pathological conditions that depend on regulators of vascular tone, blood rheological properties, or vascular wall permeability.

[0245] The biochemicals may include substances that modulate the microcavitation process, such as surfactant additives. In other words, surfactants not only affect pore formation but also facilitate the movement of signaling molecules through the porous structure. The biochemicals may include substances that replenish and maintain the tissue fluid volume within the cartilage tissue, such as dextran-based drugs. The biochemicals may include weakly ionized or deionized solutions.

[0246] The biochemicals may include saline solutions to correct the acid-base, osmotic, or ionic status of the tissue, or to alter the electrical conductivity of the tissue. The biochemicals may include gelatin-based drugs, such as gelatinol. Such drugs may affect the osmotic balance within the tissue, be a source of amino acids for collagen, and / or contribute to the replenishment or replacement of tissue fluid volume.

[0247] Biochemical substances may include substances used for diagnostic purposes, for example, to facilitate real-time information detection. In particular, biochemical substances may include radiopaque preparations, substances with fluorescent labels, optically anisotropic substances such as substances for the detection of pathological tissue changes, tissue necrotic areas, tissue ultrastructural heterogeneities associated with the uneven distribution of bubbles or pores.

[0248] As will be shown later, all of these biochemicals, such as signaling molecules, can be transported over large distances due to modulated laser light, especially with the aid of stress waves induced by the modulated laser light, which results in a larger working area for the biochemicals mentioned above.

[0249] The biochemical may be in gas or fluid form. The biochemical is delivered to the joint through the channel element 103, which forms an access channel to the region 202 within the joint 201. For example, when introducing the channel element 103 into the region 202 of the joint 201, a guidewire is placed within its lumen, the guidewire is removed from the channel element 103, and the light delivering element 102 is placed within the channel element 103 instead. The light delivering element 102 may include or be attached to a piston configured to deliver a quantity of the biochemical into the region 202. In the case of a gaseous biochemical, a gas bubble is placed near the end of the channel element 103.

[0250] In a sixth step of the method, the area continues to be irradiated with a predetermined setting combined with an additional effect exerted by the effect exerting element 104 to form a thermomechanical zone with a controlled spatial and temporal distribution of stress based on real-time detection information, generating signaling molecules or stress waves, which are configured to activate distant stem cells 204.

[0251] In particular, the effect-producing element 104 is configured to exert mechanical vibrations on the region 202. The bubbles generated in the fifth step can be separated from the end of the channel element 103 using modulated laser light and / or mechanical vibrations. The bubbles then travel within the region 202 to a certain distance from the end of the channel element 103. The travel speed, which is limited by the bubble size, is taken into account in the real-time adjustment. The feedback controller then adjusts the laser source 101 and the effect-producing element 104 to cause a more efficient distribution of the gas within the region 202.

[0252] Modulated laser light promotes the activation of biological materials, including chondrocytes and stem cells, by inducing mechanical effects. Mechanical effects can be caused, in particular, by stress waves resulting from non-uniform heating waves generated as a result of coordinated rotational vibration of water dipoles within the cartilage matrix, or stress waves generated due to the introduction of gas or liquid microbubbles into (and their subsequent migration along) the cartilage matrix, as shown in Figure 6.

[0253] The laser radiation energy is primarily absorbed by the liquid contained in the intercellular matrix of cartilage tissue. The formation of a porous structure in the fourth step may optimize the liquid content. Exposed to the laser radiation, the liquid expands and contracts unevenly, disrupting gas bubbles into numerous smaller ones. These microbubbles periodically increase and decrease in volume. The temperature gradient created by the modulated laser light drives the microbubbles to migrate toward less heated areas away from the first light-delivery element 102. This results in the diffusion of gas bubbles within the tissue, which undergoes the described effects and increases the amplitude of the pressure wave, as shown in Figure 6.

[0254] Gas bubbles, especially CO2 bubbles, form due to the temperature-dependent solubility of gases in tissue water under moderate laser heating. Temporal modulation of the laser light provides specific amplitudes and frequencies of mechanical effects due to the vibration and movement of the bubbles. Spatial modulation of laser light generated by several lasers with different wavelengths and penetration depths allows for control of the distance of mechanical wave propagation, thus enabling treatment of various targets, particularly cells and various articular tissues, including cartilage, bone, and ligaments, as well as various types of joints, including hip, knee, and elbow joints.

[0255] In particular, the combination of bubbles generated during direct thermomechanical activation and signaling molecules generated during indirect biochemical activation can further improve the effectiveness of laser therapy. For example, when exposed to laser irradiation, free radical oxidation of oxygen molecules can be activated in primary bubbles in a fluid medium, such as air bubbles. Active oxygen is formed, and as a result of electrostatic interactions with charged molecules in the intercellular matrix, the surface of the bubbles can acquire an electric charge. The electrostatic interaction between the surface of the microbubbles and the number of signaling molecules increases the active surface for intercellular receptor interactions, improving tissue metabolic activation, such as remote control of the first stem cells 204.

[0256] The surfaces of the bubbles become electrically neutral, preventing lipid peroxidation of cell membranes. This is achieved by the binding of oxygen free radicals to ionized matrix molecules. Furthermore, the porous structure facilitates the transport of molecules that interact with the bubbles and their surfaces. These molecules can be ions derived from signaling molecules or drugs.

[0257] It should be noted that the microbubbles appearing in the exposed region can be formed by different methods. For example, as outlined above, bubbles can be formed directly through the channel element 102 into the region 202, particularly the irradiated first portion 203 of the region 202, during the introduction of a gaseous biochemical, such as CO or air. Bubbles can also be formed indirectly upon the introduction of a non-gaseous biochemical, such as tissue material or a fluid substance, which promotes bubble formation in the laser-irradiated first portion 203 of the region 202. The desired effect of bubble formation can be achieved as a result of degassing of the flowing liquid medium resulting from the electromagnetic radiation of the exposed region, such as the bubble formation mechanism shown in FIG. 6. In an exemplary embodiment, a non-gaseous biochemical that promotes the formation of bubbles in the irradiated first portion 203 of the region 202 can be administered along the formed access channel.

[0258] In conclusion, the controlled formation of stabilized bubbles induced by modulated laser light based on real-time detection information can promote the generation of stress waves or increase their amplitude, facilitating the transport of chemicals, including signaling molecules and other biochemicals, and thus activating the first stem cells in the tissue, thereby enhancing the healing effect of each laser treatment step or session.

[0259] The structure of cartilage tissue is heterogeneous in terms of the distribution of its main components, such as water, collagen fibers, and proteoglycans. Its structure is also heterogeneous in terms of its thermomechanical properties. Therefore, different domains of the tissue can be distinguished. For example, each domain may contain regions with similar orientations of the dipole momentum of water molecules. The displacement of air bubbles and the formation of porous structures occur most easily along the boundaries between different domains. Water molecules can undergo rotational vibrations. The vibrational motions of different molecules can interact with each other, for example, to enhance or annihilate each other. Domains with similarly oriented dipole moments can enhance vibrational motions and promote the formation of stress waves that promote primary stem cell activation.

[0260] External effects, such as mechanical, thermal, or electrical effects exerted by the effect-producing element 104, can destroy or destabilize the domain structure, which can delay the transformation process. Therefore, exposure to external effects is reasonably provided by several series with distinct time intervals between series. This interval is necessary to restore the domain structure and reorganize the porous structure.

[0261] During one laser treatment session, the irradiated first portion 203 of the region 202 may be sequentially varied, which can be achieved via servo elements, for example under ultrasound or OCT control.

[0262] To accelerate the reorganization process of the porous structure during this time interval, it is necessary to use moderate heating, for example to maintain a temperature below 50°C. This heating can also be useful in inactivating nerve endings resulting from cartilage degeneration.

[0263] The boundaries of this additional heating zone must be tightly controlled, which is achieved by the laser system within the enclosure.

[0264] While introducing the channel element 103 with the guidewire into the joint, the channel element 103 can be driven in an oscillating motion, which can reduce damage to the tissue matrix. Local tissue damage caused by the introduction of the channel element 103 can result in a small amount of cell death. Cell death also induces the production of signaling molecules. In other words, the signaling molecules are generated solely due to the mechanical effect from the guidewire and can be transported by the stress waves induced by the modulated laser light.

[0265] The effectiveness of the method implemented by the laser system of the present disclosure is also reflected in improved laser-assisted cross-linking of collagen fibers. While cross-linking with riboflavin and blue or ultraviolet lasers has been used previously, the corresponding therapeutic effects are slow and sometimes result in side effects in the form of edema. Our approach utilizes low-intensity UV laser irradiation combined with stem cell injection, making the treatment faster, safer, and more complete.

[0266] 7. In the seventh step of the method, a graft is introduced into region 202 to repair the large defect within region 202.

[0267] 8. In the eighth step of the method, a stress distribution is detected on the implant or the defect tissue, between the implant and the defect tissue, or in the vicinity thereof. The stress may be a mismatch stress between the cartilage tissue and the implant after the implant is introduced. Then, the stress is relieved by forming a porous structure using modulated laser light.

[0268] 9. In a ninth step of the method, the laser system is displaced to another area within the joint 201 according to instructions from the feedback controller 106, and one or more of the first to eighth steps described above are repeated.

[0269] 10. In the tenth step of the method, nerve endings in the region 202 of the joint 201 are activated or deactivated as required using modulated laser light, thermal, mechanical, or chemical effects of the effect-producing element 104. This can include mechanical removal or volume reduction of objects compressing the nerve, such as muscle traps or ligaments. The objects can be removed by ultrasonic disruption, laser ablation, or other effects. This transformation can eliminate pathological swelling by reducing blood flow events. In this way, the changes in the joint macrostructure due to its remodeling, such as the regeneration of new tissue, can have an improved lasting effect.

[0270] Throughout the method, at any time the laser source 101 or the effect-producing element 104 is used. The method may include the following steps for performing real-time adjustments: a) measuring cartilage tissue modification properties including deformation, stress, temperature, structural modification, mechanical and optical properties of the tissue, and electrical impedance; b) adjusting the laser dosimetry or dosimetry of the effect-producing element 104 based on the measured parameters, in particular shutting off or switching off the laser source 101 or the effect-producing element when a predetermined threshold is reached;

[0271] It is understood that one or more of the steps described above may be performed simultaneously or in a different order than numbered.

[0272] For example, the fifth step of introducing the biochemical agent may occur before, during, or after the fourth or sixth step of irradiation. As another example, the seventh step of introducing the implant can be performed before steps two through six.

[0273] Each step may also achieve other effects of other steps, for example, stem cells or other cells may be activated to produce signaling molecules during the formation of the porous structure in the fourth or eighth step.

[0274] The method, or portions of the method, may be repeated for as many cycles as necessary. Repetition of this method step facilitates increasing the volume of gas or other substance delivered to the tissue if necessary for removal of the substance or diffusion into the joint tissue volume. Completion of the method is determined based on the detected information, for example, when a predetermined value is achieved by the detected information. The laser system is removed from the patient's body. The skin around the puncture is treated with iodine and alcohol, a sterile dressing is applied, and the patient is taken to a hospital ward.

[0275] In addition to the effects outlined above, modulated laser light may have other additional positive effects on cartilage tissue.

[0276] For example, intracellular Ca 2+ This may promote the release of chondrocytes, which in turn may promote the regeneration or rejuvenation of the cell population as a result of the control of apoptotic death of inactive chondrocytes.

[0277] As another example, it may promote an increase in the functionally active surface of cell membranes, enhancing cell-cell interactions.

[0278] The combination of all the possible positive effects of modulated laser light results in the replacement of pathologically altered joint or articular cartilage with younger or newly formed cartilage tissue, i.e., improved regeneration of damaged or lost structures compared to conventional techniques. The newly formed hyaline cartilage in the joint fills in the pathologically altered areas of the joint surface resulting from degenerative or traumatic diseases such as osteoarthritis, chondromalacia, and joint trauma. This provides a clinically significant restoration of functional joint activity.

[0279] Typical Algorithms As outlined above, the modulated laser light used in the present disclosure can alter thermodynamic parameters in the joint region. The most significant changes in parameters can be attributed to structural and phase transformations that occur in the tissue during laser irradiation. In particular, the nonlinear nature of the mathematical problem makes it difficult to provide accurate calculations in real time using existing medical equipment associated with internal conventional computers. A remote high-performance computer provides accurate calculations of these changes.

[0280] A typical algorithm can be characterized by the mathematical problems and sub-problems that need to be solved by the feedback controller 106 for real-time adjustment of the laser system. The mathematical problems, sub-problems, and tasks may include: 1. 3D thermomechanical problems taking into account the thermal expansion of various three-dimensional objects.

[0281] 2. 3D dynamics of laser-induced bond breaking with allowance for partial bond recovery.

[0282] 3. Accurate calculation of laser heat source based on the problem of light propagation and absorption in different structures of the joint.

[0283] 4. Proper calculation of laser heating. 3D unsteady thermal problems for spatial and temporal modulation of laser sources consider both linear and nonlinear terms for laser-induced phase transformations of tissues, such as tissue degeneration induced by laser light.

[0284] 5. Kinetics of porous structure formation, including pore branching and merging. Figure 7 shows an example of pore size dynamics calculated in real time.

[0285] 6. Calculation of the kinetics of tissue degeneration and the range of safe laser dosimetry to minimize tissue degeneration.

[0286] The algorithms used in this disclosure should solve the inverse problem of determining the dosimetry of the laser source 101, the dosimetry of the effect-producing element 104, and / or the dosimetry of the biochemical introduction to achieve a desired positive effect, such as stress wave generation, while minimizing negative effects, such as overheating.

[0287] Examples of successful treatments The present disclosure has been embodied in certain preliminary experiments disclosed below. Although the present disclosure has been embodied in these examples, these examples may include additional steps, which should not be construed as limiting the present disclosure.

[0288] First Example Two-year-old minipigs underwent surgery under ketamine anesthesia after romifidine sedation. Two defects measuring 4 x 6 mm and 0.5 mm deep were created on the cartilage of the medial femoral condyle. The ligaments of the knee joints of both hind limbs (left and right) were partially amputated. After surgical creation of the defects, the animals were subjected to forced movement on the joints for 56 days. On the 57th day, the left joint was opened, leaving the right joint as a control. Visual observation showed that the surgically created defect did not change in size, but an additional secondary defect of irregular shape and larger size (approximately 7 x 15 mm) appeared approximately 2 mm from the primary defect on the surface of the cartilage in the area of ​​maximum mechanical load during movement. Severe edema was observed around the damaged ligaments.

[0289] The left joint was treated according to the following protocol: First, diagnostic parameters such as elastic modulus and electrical impedance were measured by a feedback control system using optical coherence elastography and electrical measurements to establish initial dosimetry for laser treatment. A laser device including a 1440 nm diode laser source 101, a detection element 105 configured to perform OCE and impedance measurements, and a feedback controller 106 for real-time adjustments was used to perform a first set of laser treatments to form porous structures in the cartilage plate and periosteum. The initial dosimetry of the laser source included a 0.8 W power output, a 200 ms pulse duration, a 2.5 Hz pulse repetition rate, 10 pulse trains, and 6 seconds between trains. The feedback controller 106 stopped irradiation when the preset parameters of elastic modulus and electrical impedance were achieved. In the second step, the damaged area of ​​the ligament was hydrated with 0.1% riboflavin, and a laser beam with a wavelength of 368 nm (corresponding to one of the riboflavin optical absorption peaks) and an irradiation diameter of 7 mm was applied at ~10 mW / cm. 2 The ligament was then irradiated for 20 seconds at 1000 W to form additional reinforced crosslinks between collagen fibers within the ligament. In the third step, the defect was hydrated using bone marrow aspirated from the animal's sternum. In the fourth step, the cartilage at the border of the secondary defect was irradiated with laser light at a wavelength of 1440 nm, an initial laser power of 0.5 W, a spot diameter of 0.6 mm, a distance between laser spots of 3 mm, a pulse duration of 70 ms, a pulse repetition rate of 1 Hz, and a series of eight pulses with a 5-second interval between the series. The laser power during treatment was controlled by a remote high-performance computer based on the light scattering characteristics measured in real time by the detection element 105, maintaining the amplitude of the vibration pressure in the range of 5–15 kPa. The total exposure time for each spot was also controlled by a feedback controller, which stopped the irradiation when the specified parameters were reached.

[0290] After 52 days of treatment, the animals were sacrificed and visual and morphological analyses were performed. In the treated joints, (i) both the irradiated (secondary) and non-irradiated (primary) lesions were found to be covered with cartilage-like tissue, (ii) the ligament appeared nearly normal without visible edema, and (iii) the coverage of the lesion was more complete and approximately three times faster than that achieved by laser-induced regeneration without additional crosslinking and stem cell impregnation and activation.

[0291] Figure 5 demonstrated structured illumination microscopy (SIM) images showing the formation of porous structures and gas bubbles in the laser-treated cartilage plates.

[0292] Tissue sections (4–5 μm thick) were prepared using a Leica CM1900 cryomicroscope at -15°C using the refrigerant Jung Tissue Freezing Medium. Ca2+ ions were detected using Fluo-4 Ca dye (Thermo Fisher Scientific, USA). Images were obtained using a super-resolution microscope, the Optical Microscopy Experiment (OMX) System v3.0 (Applied Precision, Inc., GE Healthcare). A 532 nm laser was used for fluorescence excitation, and the refractive index of the objective immersion oil was 1.514. Super-resolution fluorescence images were reconstructed using softWoRx 2.0 (Applied Precision, Inc.) using the raw data collected by OMX. Reconstructed images were post-processed and displayed using ImageJ.

[0293] Histological analysis demonstrated the prevalence of hyaline and fibro-hyaline cartilage in both areas of injury (primary and secondary) with repair of the splenic lamina (LS), which has not been achieved previously using any other technique. Figure 8 demonstrates histological images of minipig articular cartilage, the injured area, and the treated area 52 days after treatment.

[0294] Although LS is crucial for providing the lubrication and mechanical properties of articular cartilage, it does not recover after replacing the damaged area with fibrous cartilage or fibrous connective tissue. The recovery of LS is important evidence of the advanced regeneration properties under laser irradiation combined with bone marrow stem cell injection. Therefore, this example clearly demonstrates that the combination of different real-time modulated laser beams and biochemical signals detected from different targets (cartilage plate, stem cells, and ligaments) results in laser-induced regeneration of crosslinks resulting from activated stem cells. This allows for rapid and more complete repair of the joint with a high prevalence of hyaline cartilage. Figure 9 demonstrates an electron micrograph of articular cartilage growing in the treated lesion. The untreated joint (shown in Figure 8a) maintained its damaged state with osteoarthritic areas and necrotic tissue. Note that simple laser treatment restored the damaged joint of a miniature pig within six months (three times longer than in this example).

[0295] Second Example A 64-year-old patient had suffered from knee pain for 6 years. There had been prolonged periods of exacerbation over the past 1.5 years. X-rays revealed signs of osteoarthritis of the knee. MRI revealed changes in the vitreous plate, the latter thinning and displaying pathological "fringing." The diagnosis included osteoarthritis of the knee and femoro-patellar joint stage II, medial meniscus stage III and lateral meniscus stage III damage, Stoller's classification, subtotal anterior cruciate ligament rupture, lateral collateral ligament injury, and degenerative changes of the medial collateral ligament. There was thinning and rupture of the medial collateral ligament, and focal periarticular swelling. A Baker's cyst (73 x 14 mm) was also present.

[0296] The treatment was performed in several stages. Under local anesthesia with lidocaine and bupivacaine, arthroscopy of the knee joint was performed with sufficient saline injection to create an outflow channel from the knee joint. A first light delivery element 102, in this case an optical light guide, was introduced through a channel element 103, in this case an endoscope.

[0297] Laser irradiation of the fringe-coated surface was performed with the following parameters: irradiation wavelength 2.09 μm, pulse duration 500 μs, pulse sequence frequency 10 Hz, irradiation sequence duration 10 s, interval between irradiation sequences 10 s, initial power 3 W, and total irradiation time 8 min.

[0298] The laser output during treatment was controlled by a remote high-performance computer 106d based on light scattering and speckle dynamics measured in real time by the detector element 105. The feedback controller 106 adjusted the system to maintain the amplitude of the vibration pressure in the range of 5–15 kPa. The total exposure time and fringe smoothing were controlled using the feedback controller 106. A pulsatile flow of fluid (saline) through the knee joint area was maintained during irradiation. During the next phase of treatment, 5 ml of bone marrow aspirate was injected into the joint. During the final phase of treatment, a high-frequency current source was introduced into the joint, and the articular surface and cartilage plate were irradiated with the following parameters: frequency 2 MHz, exposure sequence duration 5 seconds, and interval between sequences 5 seconds. The radiation power was controlled using the feedback controller 106 based on light scattering and photoacoustic temperature measurements. The temperature of the impact zone reached 42 °C and was maintained at this value with an accuracy of ±0.3 °C for 25 seconds for each impact zone. During exposure, a flow of fluid (saline) was maintained along the articular surface through the area of ​​the glass plate. A total of four zones were treated.

[0299] In the post-treatment period, there was significant improvement. Three weeks after treatment, there was a significant reduction in pain during walking. The pain completely stopped after two months. A 12-month MRI showed thickening of the cartilage plate, significant reconstruction of the posterior cruciate ligament and partial reconstruction of the anterior cruciate ligament, no perifocal edema, and a 40% reduction in the size of the Baker's cyst. The patient returned to normal life and activities. This case demonstrated rapid pain relief and significant repair (supported by MRI evidence) of the knee joint, including the cartilage plate and ligaments.

[0300] Third Example A 59-year-old patient had been suffering from back pain syndrome for over 8 years, with regular attacks of back pain. Exacerbations continued for several months. Conservative treatment was successful in the majority of cases. Sanatorium-resort treatment was performed regularly over the past 4 years. Last year, leg pain increased sharply, and neurogenic intermittent claudication syndrome developed.

[0301] MRI was used to examine images of an elderly patient with lumbar spondyloarthropathy, revealing spinal canal stenosis at the L3-L4, L4-L5, and L5-S1 levels. The primary causes of the stenosis were L3-L4 disc protrusion and bilateral hypertrophy of the ligamentum flavum. The spinal canal size was 8 mm. At the L4-L5 level, the stenosis was associated with a dural sac, a central 8 mm disc herniation, thickened joints, and rough compression of the smooth ligament. The spinal canal size was 5 mm.

[0302] CT scans detected a "vacuum effect" at this level. At the L5-S1 level, spinal channel stenosis was caused by disc protrusion and gross hypertrophy of the ligamentum flavum, with signs of retrograde degeneration at this level. Signs of joint hyperplasia and hypertrophy were present. The spinal channel size at this level was 9 mm.

[0303] Under general anesthesia, the treatment was carried out in several steps: Microdisc compression was performed at the L3-L4, L4-L5, and L5-S1 levels, and compression of the dural sac and nerve roots by thickened areas of the ligamentum flavum and facet joints was eliminated at all levels.

[0304] The manipulation of the intervertebral disc and vertebral joint was then performed.

[0305] L3-L4 disc: A disc puncture was performed, but there was no disc tension. Discography showed a rupture of the annulus fibrosus in the zone of the left lateral disc section and paravertebral penetration of radiopaque material. 0.5 cm 3A chondroitin sulfate-based gel was injected into the disc space. A light guide was then introduced into the disc (using the same needle) and irradiated with a 1.56 micron laser wavelength in five zones. The irradiation time for each zone was automatically determined using a feedback controller 106, which turned off the radiation 1 second after turbulence occurred in the exposure zone. The occurrence of turbulence was recorded using caking picture dynamics. The radiation power was initially set to 0.7 W and then automatically changed using the feedback controller 106, which turned on temperature measurement, so that the temperature of the exposure zone was maintained at 46°C with an accuracy of ±0.5°C.

[0306] L4-L5 intervertebral disc: A free sequestrant (2 cm in size) was removed from below the longitudinal ligament. The disc space was irrigated with NaCl solution (0.5%). Endoscopy revealed a large defect in the hyaline lamina in the central region of the L5 vertebral body and disruption of the annulus fibrosus throughout the disc. Laser irradiation of the disc in six zones was performed.

[0307] A laser with a wavelength of 1.32 microns was used. The zone irradiation time was automatically determined using a feedback controller 106, which turned off the radiation after the appearance of porous structures (micropores) in the irradiation zone. The appearance of the micropores was recorded using optical coherence tomography. A biological tissue suspension (stem cells collected from the same patient during sternal puncture) was then injected into the disc space.

[0308] L5-S1 intervertebral disc: After removing fragments of the annulus fibrosus from both sides and forming a bed, a B-Twin cage was introduced into the disc space. The remaining disc elements were then laser-irradiated in three zones on the right and three zones on the left. The L3-L4, L4-L5, and L5-S1 facet joints were also exposed to laser irradiation at a wavelength of 1.44 microns after puncture and air introduction. The irradiation time for each zone was automatically determined using a feedback controller 106, which turned off the irradiation 2 seconds after microbubbles formed in the exposure zone. Microbubble formation was recorded using an acoustic transducer. The radiation power was initially set to 1 W and then automatically changed using the feedback controller 106, which turned on photoacoustic temperature measurement to maintain the temperature in the exposure zone at 42 °C with an accuracy of ±0.3 °C.

[0309] During the post-treatment period, significant improvements were observed: leg pain on weight bearing disappeared and the lumbar pain syndrome decreased. Restriction of physical load and wearing a corset were recommended for 2.5 months after the laser procedure. During this time, no exacerbation of pain was observed. Examinations at 6 months and 1 year showed no signs of spondyloarthropathy at L3-L4 and L4-L5 (MRI), and no signs of joint hypertrophy or destruction.

[0310] Fourth Example A 9-year-old Irish Sport Horse presented with severe gelation of a 3 / 5 lame on the left hip joint, beginning after turning out. There was moderate bony proliferation on the medial aspect of the left hind femoral joint, with an angular bone fragment on the medial dorsal aspect of the P1 articular margin. Bone density at the mid-distal aspect of the left third metatarsal was slightly heterogeneous with focal radiolucencies. There was moderately increased soft tissue opacity within the femoral joint. Multiple pinpoint mineral opacities were present in the plantar soft tissue, overlying the articular joint. The diagnosis was (i) moderate osteoarthritis of the left femoral joint with synovitis / joint effusion, (ii) a large (20 x 30 mm) defect of the cartilage plate, and (iii) tendon and ligament damage.

[0311] Treatment was performed in several stages under ultrasound imaging and ketamine anesthesia after romifidine sedation. First, the horse was injected with prostride (autologous conditioned plasma) into the actual joint. Laser treatment was then performed using a laser system employing two laser sources 101 with wavelengths of 720 nm and 1320 nm, pulse durations of 500 ms and 20 ms, and pulse repetition rates of 0.25 Hz and 2 Hz, respectively. Initially, the radiation power was set to 2 W and then varied using a feedback controller 106 based on photoacoustic and light scattering measurements. Laser treatment was performed offline using a predefined setting table for laser settings that provided the desired spatial distribution of porous structures (micropores) that enhance water permeability and cell supply (see Figure 7). Three series of six laser pulses, spaced 5 seconds apart, were applied to each zone around the lesion. Twenty elliptical zones with a 3.5 mm distance between zones were treated.

[0312] In the next step, a liquid, fast-setting implant made from silk fibroin and stem cell-containing hyaluronic acid hydrogel was introduced into the lesion. After 12 minutes, laser treatment was performed using laser radiation with a wavelength of 1560 nm, a pulse duration of 200 ms, and a pulse repetition rate of 0.5 Hz to relieve mismatch stress at the implant-cartilage interface. The laser power and exposure time were controlled by a feedback controller 106, which measured temperature by photoacoustics and residual stress by optical coherent elastography.

[0313] Significant improvement was observed during the post-treatment period. Lameness significantly improved after 40 days of treatment and nearly disappeared after two and a half months. CT data showed no signs of osteoarthritis or joint effusion, an almost complete absence of osteophytes, and a significant reduction in synovial calcification. MRI showed good graft survival and nearly complete recovery of tendons and ligaments. Thus, by three months, significant improvement had been achieved, including in areas adjacent to the laser-irradiated area.

[0314] The description of specific embodiments and drawings merely serves to illustrate the technology of the present disclosure and its associated advantageous effects, and should not imply any limitations, the scope of the present disclosure should be inferred from the appended claims. [Explanation of symbols]

[0315] 101 Laser Source 102 Light Delivery Element 103 Channel Elements 104 Effect Factors 105 Detection Elements 106 Controller 106a Diagnostic Elements 106b Feedback control element 106c Radiation Modulation Factor 106d Remote Ultra-High Speed ​​Computer 201 joints 202 areas 203 First Part 204 First Stem Cells

Claims

1. 1. A laser system suitable for treating cartilage tissue within a joint (201), comprising: a laser source (101); a feedback controller (106) configured to adjust the dosimetry of the laser source (101) to generate spatially and / or temporally modulated laser light; a first light delivery element (102) configured to direct the spatially and / or temporally modulated laser light to a region (202) within the joint (201) and illuminate a first portion (203) of the region (202); a sensing element (105) configured to sense one or more physical, chemical, mechanical and / or structural properties in said region (202) in real time and generate real-time sensing information; Equipped with the feedback controller (106) is configured to adjust the dosimetry of the laser source (101) in real time based on the real-time detected information regarding the one or more physical, chemical, mechanical and / or structural properties within the region (202) for controlled activation of stem cells (204) outside the first portion (203) of the region (202) to form hyaline cartilage tissue; the feedback controller (106) is configured to adjust the dosimetry of the laser source (101) so that the generated modulated laser light changes the temperature and / or stress of tissue in the first portion (203) of the region (202) in a specific sequence and / or simultaneously. Laser system.

2. a channel element (103) configured to form an access channel to the region (202) within the joint (201); the channel element (103) is configured to deliver pre-activated stem cells to the region (202); the first light delivering element (102) is configured to direct the spatially and / or temporally modulated laser light through the channel element (103) to the first portion (203) of the region (202); 10. The laser system of claim 1.

3. the feedback controller (106) is further configured to control in real time the position of the first light delivering element (102) within the region (202) during irradiation based on the real-time detected information.

10. The laser system of claim 1.

4. the feedback controller (106) is further configured to adjust the dosimetry of the laser source (101) based on the real-time detection information for controlled formation of a porous structure on cartilage tissue and / or another object in the region (202).

10. The laser system of claim 1.

5. the first light-delivery element (102) is configured to irradiate the first portion (203) of the region (202) to induce the formation of tissue bridges between the implant and the cartilage tissue within the region (202); 10. The laser system of claim 1.

6. the feedback controller (106) is further configured to adjust the dosimetry of the laser source (101) based on the real-time detection information for controlled formation of a porous structure on cartilage tissue and / or another object in the region (202); the sensing element (105) is configured to sense a stress distribution at or near the interface between the implant and the cartilage tissue; the feedback controller (106) is configured to control the laser source (101) and the first light-delivery element (102) according to the detected stress distribution to form the porous structure at or near the interface between the implant and the cartilage tissue.

6. The laser system of claim 5.

7. an effect-producing element (104) configured to produce a thermal, electrical, magnetic, and / or mechanical effect on tissue within the region (202), and the feedback controller (106) is configured to adjust the effect-producing element (104) in real time based on the real-time detected information.

10. The laser system of claim 1.

8. The feedback controller (106) is configured to adjust the laser source (101) and / or the effect-producing element (104) to activate or deactivate nerve endings in real time based on the real-time detection information.

8. The laser system of claim 7.

9. the feedback controller (106) comprises a remote high performance computer, a remote hybrid quantum-classical computing facility, and / or a remote quantum computer (106d), and / or is coupled to the remote high performance computer, the remote hybrid quantum-classical computing facility, and / or the remote quantum computer; and / or the feedback controller (106) comprises and / or is connected to a storage device, the storage device storing an offline configuration table, the configuration table being calculated by a remote high performance computer, a remote hybrid quantum-classical computing facility, and / or a remote quantum computer (106d); 10. The laser system of claim 1.

10. 1. A method for detecting and processing information, comprising: a) detecting one or more physical, chemical, mechanical and / or structural properties of tissue in a region (202) within a joint (201) and generating detected information; b) processing said detected information regarding said physical, chemical, mechanical and / or structural properties of said tissue in said region (202) in said joint (201); c) acquiring in real time, during the stress wave generation, signal molecule generation, and / or porous structure formation, the properties of the stress wave generation, stress wave propagation, signal molecule generation, signal molecule transport, and / or porous structure formation in the region (202) of the joint (201), method.

11. processing the detection information, generating a dosimetry value of the laser source (101) in real time based on the detected information regarding the physical, chemical, mechanical and / or structural properties in the region (202) within the joint (201); The method of claim 10.

12. Detecting the physical, chemical, mechanical and / or structural properties in the region (202) within the joint (201) comprises: detecting a temperature in the region (202) within the joint (201), wherein the dosimetry of the laser source (101) is generated when the temperature is within a predetermined range. The method of claim 11.

13. and acquiring a characteristic of said crosslinking of the tissue in real time during crosslinking.

13. The method according to any one of claims 10 to 12.

14. detecting a stress distribution at or near the interface between the cartilage tissue and the implant; The method of claim 13.

Images