A system for detecting the degradation rate of an injectable hydrogel wound dressing

Abstract

The present application relates to the technical field of material analysis, and discloses a system for detecting the degradation rate of an injectable hydrogel wound dressing, comprising: a hydrogel-tracer composite structure, release of the tracer of which is controlled by a critical size relationship between particle size and dynamic pore size of the gel, an in-vitro optical probe module and a data processing module, the modules first perform in-vivo self-calibration through a photothermal effect response to determine a real initial reference, and then monitor optical signal attenuation based on the reference to determine the degradation rate, the present application converts a chemical degradation process that is difficult to directly observe into a physical diffusion event that can be stably characterized by an optical signal, is independent of specific chemical components, and has a measurement result that is directly related to material structural integrity, thereby solving the problem of the prior art that information correlation is not directly related and applicability is limited.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of injectable hydrogel wound dressing degradation rate detection system, belong to material analysis technical field. BACKGROUND

[0002] At present, the performance change of material in specific application environment is characterized by specific physical or chemical means, which is the conventional technical means in this field. For degradable materials used in vivo, real-time acquisition of the change information of its structural integrity is of great technical significance for evaluating its functional period and guiding clinical application.

[0003] When the application object is a kind of medical dressing such as injectable hydrogel, the conventional analysis method has limitations. This kind of material is usually composed of polymer network and water. When it degrades in vivo, the breaking process of molecular chain itself does not produce characteristic optical or acoustic signals that can be recognized by in-vitro detection equipment, which makes it difficult to effectively apply the traditional monitoring principle that relies on the response signal emitted by the material itself, and the structural state of the material in vivo is difficult to be accurately known.

[0004] To solve this problem, the prior art attempts to use medical imaging methods for indirect observation, but such methods can only reflect the macroscopic volume change of the material, and there is no precise correspondence between the volume change of the material and the true integrity of its network structure. For example, tissue edema or material swelling can cause volume change, which brings uncertainty to the accurate judgment of whether the material has structural failure due to degradation. Specifically, the prior art mainly has the following technical problems: 1. The correlation between the measured information and the degradation of the material is not direct, and it is easy to be disturbed by other physiological factors; 2. The monitoring has a lag, and it is usually difficult to effectively monitor the early change of the structural integrity of the material; 3. The applicability is limited, and there is no universal rule for the correlation between volume change and degradation degree, which is difficult to be used for standardized evaluation among different materials. It can be seen that the prior art path has not solved the core technical problem that the monitoring information comes from the inside of the material, and the material itself does not produce direct signals during the degradation process. Therefore, how to establish a new analysis method to obtain internal information directly related to the network structural integrity of the material in real time without changing the chemical components of the general hydrogel material has become a technical problem to be solved by the present application. SUMMARY

[0005] The present application provides a kind of injectable hydrogel wound dressing degradation rate detection system, which is mainly used to solve the problem that the prior art cannot non-invasively and in real time monitor the degradation state of general hydrogel dressing that does not produce characteristic signals in vivo, which is directly related to the structural integrity.

[0006] To achieve the above purpose, the present application provides a kind of injectable hydrogel wound dressing degradation rate detection system, which comprises:

[0007] A hydrogel-tracer composite structure formed by in vivo solidification of a physically mixed injectable hydrogel precursor and tracer particles, a pre-set physical critical size correspondence between the particle size of the tracer particles and the pore size of the hydrogel network dynamically evolving during degradation is established, which enables the transition of the tracer particles from a physically entrapped state to a releasable state only when the pore size evolves to a critical size larger than the particle size; an in vitro optical probe module configured to emit electromagnetic radiation of a predetermined wavelength to an in vivo region where the hydrogel-tracer composite structure is implanted, and to detect optical signals caused by the concentration change of the tracer particles; a data processing module configured to: firstly execute a self-calibration mode in which the in vitro optical probe module is controlled to emit high-energy light pulses, and to determine a reference value representing the real initial state of the hydrogel-tracer composite structure in vivo based on the detected transient optical response characteristics caused by the photothermal effect of the tracer particles; and then execute a regular monitoring mode in which the decay rate of the optical signals over time is determined based on the reference value of the real initial state, and the decay rate is processed as the degradation rate of the hydrogel.

[0008] Preferably, the data processing module is further configured to: perform frequency domain analysis on the optical signals detected by the in vitro optical probe module to extract a physiological indicator representing the local tissue blood perfusion state in a pre-set heart rate frequency range covering 0.8 Hz to 2.5 Hz wherein, wherein, is the signal energy of the optical signals in the heart rate frequency range, is the signal energy of the direct current component of the optical signals; and based on the synergistic changes between the acceleration of the degradation rate and the sustained increase of the physiological indicator, a complication risk warning is generated.

[0009] Preferably, the tracer particles comprise at least two tracer components with different release kinetics, wherein the first tracer component is a free-state tracer particle, and the second tracer component is a slow-release state tracer particle encapsulated in a degradable microsphere; and the data processing module is further configured to determine the early stage and the late stage of the hydrogel degradation process by analyzing the optical signal change curve with a biphasic decay pattern formed by the sequential release of the at least two tracer components.

[0010] Preferably, the extracorporeal optical probe module further comprises an ultrasonic transducer integrated coaxially with the electromagnetic radiation emitter; and the data processing module is further configured to control the extracorporeal optical probe module to emit nanosecond-level pulsed light to excite the generation of photoacoustic signals at the tracer particles, receive the photoacoustic signals through the ultrasonic transducer, and discriminate whether the tracer particles are in the confined state within the hydrogel network or in the released state outside the network based on the amplitude and spectral characteristics of the photoacoustic signals, and further correct the determined degradation rate of the hydrogel based on the discrimination results.

[0011] Preferably, the system is further configured to detect and analyze a transient response waveform associated with the macroscopic deformation of the hydrogel tracer composite structure caused by the mechanical disturbance on the optical signal, and determine a mechanical indicator representing the structural integrity of the hydrogel tracer composite structure based on the amplitude and rate of change characteristics of the transient response waveform in response to a standardized external mechanical disturbance applied to the in-vivo region.

[0012] Preferably, the electromagnetic radiation emitted by the extracorporeal optical probe module is broadband electromagnetic radiation covering the near-infrared waveband; and the data processing module is further configured to analyze the signal intensity at a preset wavelength related to the absorption characteristics of water molecules and the signal intensity at a reference wavelength in the optical signal, and determine an indicator representing the tissue edema state of the in-vivo region based on the change in the ratio of the two.

[0013] Preferably, the tracer particles are biocompatible inert particles with near-infrared absorption or scattering characteristics.

[0014] Preferably, the extracorporeal optical probe module comprises a light-emitting diode for emitting electromagnetic radiation and a photodiode for detecting the optical signal.

[0015] Preferably, the transient optical response characteristic is the fluctuation echo of the backscattered light signal caused by the transient thermal-elastic deformation of the microenvironment around the tracer particles immediately after the high-energy light pulse.

[0016] Preferably, the data processing module is further configured to convert the decay rate of the optical signal into the equivalent mass loss rate of the hydrogel through a preset calibration model.

[0017] Compared with the prior art, the present application has the following beneficial effects:

[0018] 1、Establish a direct conversion path between the chemical state of the material and the physical signal, by physically trapping inert optical tracers with a specific particle size in the network after the hydrogel solidifies, using the gradual increase in network pore size during gel degradation as the only release trigger, so that a molecular chain rupture process that is difficult to directly observe at the chemical level is converted into a tracer diffusion process that can be characterized by the rate of change of the optical signal at the physical level. This way avoids the complexity and uncertainty of relying on chemical reactions between degradation products and specific reagents, providing a stable and clear physical basis for monitoring the evolution of material structural integrity.

[0019] 2、The measurement principle of the present application does not depend on the chemical composition of the specific hydrogel or the specificity of the degradation product, but shifts the monitoring focus to the physical integrity changes of the three-dimensional structure of the hydrogel network; since the release behavior of the optical tracer is only determined by the relative relationship between its own particle size and the pore size of the gel network, this system can be applied to any commercial hydrogel dressing that meets the physical trapping conditions, providing a unified degradation state evaluation method for lateral comparison for different types and formulations of hydrogel materials, solving the technical limitations of existing detection methods that usually require special design or labeling for specific materials.

[0020] 3、The optical signal change rate obtained by the system directly represents the rate of the physical process of tracer escaping from the gel network, and this physical process occurs with the evolution of network pore size, so the signal rate is closely related to the structural integrity decay process of the hydrogel network skeleton in time synchronization. Compared with the evaluation method by observing the volume change of the implanted object and other indirect morphological indicators, the tracer loss event monitored by the present application is more closely related in time and cause and effect to the loss of hydrogel network integrity, eliminating the interference of volume changes caused by tissue edema and other non-degradation factors on the measurement results, so that the judgment of the functional state of the material is based on a more direct physical process. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 The working principle diagram of the detection system of the present application;

[0022] Figure 2 The state transition diagram of the system of the present application;

[0023] Figure 3 The logic judgment and generation timing diagram of the risk early warning of the present application. DETAILED DESCRIPTION

[0024] In order to make the technical solutions and advantages of the present application clearer, the technical solutions of the present application will be described in detail below. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the present application.

[0025] The present application discloses a kind of injectable hydrogel wound dressing degradation rate detection system, it is by hydrogel-tracer composite structure, in vitro optical probe module and data processing module;Work, hydrogel-tracer composite structure as measured object, in vitro optical probe module is used to collect optical signal, data processing module is handled to determine degradation rate to the signal collected, jointly constitute a complete system for determining the physical property change of material;In the application of state monitoring to hydrogel dressing implanted in body, a technical problem is difficult to establish accurate measurement benchmark, specifically, manual mixing and injection process in clinical operation, the actual initial concentration of tracer particles implanted in body and its theoretical value between deviation, and then introduce systematic measurement error;To deal with this problem, the data processing module of the present application is configured to first execute a self-calibration procedure before routine monitoring;Under the procedure, data processing module controls light-emitting diode in in vitro optical probe module, emits a high-energy light pulse to implantation area, for example, the light pulse with 50ms duration and 100mJ total energy;The light pulse is absorbed by tracer particles in hydrogel-tracer composite structure to produce photothermal effect, causing transient thermoelastic deformation of microenvironment around tracer particles;This deformation produces a fluctuating echo of backscattered light signal on photodiode of in vitro optical probe module, which occurs immediately after high-energy light pulse;Data processing module captures this fluctuating echo waveform and calculates its integral area, a transient optical response characteristic, and according to the function relationship between the integral area value and the real concentration of tracer particles calibrated in advance, a benchmark value representing the real initial state in vivo is calculated By executing the self-calibration procedure, an initial benchmark derived from in vivo physical measurement can be established for subsequent rate analysis to correct measurement deviation introduced by initial state uncertainty.

[0026] Considering the optical property differences of overlying tissues of different individuals or different implantation sites, which can introduce variables to the measurement of this transient optical response characteristic, to eliminate the influence of the variable on the determination of the benchmark value , the function relationship is constructed as a multivariate calibration model containing tissue optical parameters;The establishment procedure of the model is as follows: in offline calibration stage, a series of tissue phantoms with different and known effective optical attenuation coefficients are used, and the effective optical attenuation coefficient of each specific under the tissue phantom, a plurality of hydrogel samples with different known tracer concentrations are prepared and measured, and the transient optical response characteristic value S is recorded, thereby obtaining a three-dimensional data set containing , , ) wherein is the true concentration of tracer particles; a multivariate regression analysis technique such as response surface method is used to fit the data set to establish a calibration model ; when performing in-vivo self-calibration, the system first quickly and non-invasively obtains the effective optical attenuation coefficient of the overlying tissue at the current implantation point by spatially resolved diffuse reflectance measurement method , then obtains the transient optical response characteristic value S by high-energy light pulse excitation , and finally substitutes the on-site measured data pair , ) into the above calibration model to calculate the true initial state reference value corrected by individualized tissue characteristics .

[0027] After establishing the reference value of the true initial state, the system enters the regular monitoring mode, in which the in-vitro optical probe module periodically emits low-power probe light and detects the optical signal caused by the change in tracer particle concentration ; the data processing module calculates the normalized optical signal decay rate based on the reference value , and converts the optical signal decay rate into the equivalent mass loss rate of the hydrogel according to a preset calibration model; the hydrogel-tracer composite structure is prepared by physically mixing the tracer particles with the injectable hydrogel precursor and then solidifying in vivo to form, wherein the hydrogel network serves as the matrix material to be analyzed, and the tracer particles, such as biocompatible inert particles with near-infrared absorption or scattering properties, serve as signal probes; the setting of the particle size of the tracer particles needs to follow a calibration procedure to establish a physical critical size correspondence; the procedure requires structural characterization of the target hydrogel material to determine its average network pore size in the undegraded state and the average network pore size at the preset functional failure point ; the selection of the particle size of the tracer particles is based on the constraint condition that ; if the particle size is less than , the tracer will leak in the early stage of gel solidification, and if the particle size is greater than , which is unable to be released after the gel function has been significantly lost, this size range can make the physical entrapment-critical release mechanism work effectively, transforming the chemical degradation process into a physical diffusion process that can be characterized by optical signals.

[0028] To correlate the preset function failure point with a determined critical network pore size , and thus provide a quantifiable selection window for the particle size of the tracer particles , the following offline calibration procedure needs to be performed; first, determine the quantitative indicator of the function failure of the hydrogel dressing according to its intended mechanical application scenario, for example, define the failure threshold as the time when the storage modulus drops to 20% of the initial value; then, prepare a series of hydrogel samples with different degradation time points through in vitro accelerated degradation experiments, and simultaneously perform two measurements on each sample: measure the storage modulus of the sample by a rheometer, and obtain the average network pore size of the sample by scanning electron microscope image analysis; then, perform function fitting on the obtained multiple sets of data pairs to establish a quantitative relationship model between the storage modulus and the average network pore size ; finally, substitute the preset storage modulus failure threshold, i.e., 20% of the initial value, into the relationship model to calculate the unique corresponding critical network pore size , which, together with the initial average network pore size of the hydrogel in the undegraded state, constitutes the constraint condition for the particle size of the tracer particles , i.e. , this procedure converts the particle size selection from a functional description to a deterministic process based on objective physical quantity measurement.

[0029] In some applications that require stage-by-stage analysis of the degradation process, the tracer particles can be configured to contain at least two tracer components with different release kinetics characteristics; for example, the first tracer component is a free-state tracer particle, such as a silica microsphere with a particle size of 500 nm, and the second tracer component is the same tracer particle but encapsulated in a degradable microsphere (such as a PLGA microsphere) with an average particle size of 5 µm and a slower degradation rate, forming a slow-release state tracer particle; after implantation, with the initial degradation of the hydrogel network, when the pore size of the hydrogel network is large enough to release the free-state tracer particles, the first wave of optical signal attenuation occurs; then, the PLGA microsphere itself degrades and breaks, releasing the internal tracer particles, forming the second wave of optical signal attenuation; the data processing module analyzes the optical signal change curve formed with the two-phase attenuation morphology, for example, fits the curve with a double-exponential decay function , and obtains the fitting parameters and The characteristic rate of the early and late stages of the degradation process of the hydrogel is determined respectively; in order to deal with the signal artifacts caused by the false release or false aggregation of the tracer, the in-vitro optical probe module can further comprise an ultrasonic transducer coaxially integrated with the electromagnetic radiation emitting source; the data processing module is correspondingly configured to periodically perform state discrimination, in which process, the in-vitro optical probe module is controlled to emit nanosecond pulse light to excite a photoacoustic signal at the tracer particles; the photoacoustic conversion efficiency of the tracer particles is related to the acoustic impedance and heat capacity characteristics of their microenvironment; when the tracer particles are trapped in the hydrogel network, their thermal elastic expansion is restrained, and the generated photoacoustic signal has a high amplitude and a specific high-frequency spectral characteristic, while when they are released into the surrounding body fluid or phagocytosed by cells, the amplitude and spectrum of their photoacoustic signal will change; the ultrasonic transducer receives this photoacoustic signal, and the data processing module discriminates whether the tracer particles are in a trapped state or a released state based on the amplitude and spectral characteristics of the photoacoustic signal, and generates a weight coefficient based on this discrimination result to correct the degradation rate determined in the conventional monitoring mode.

[0030] The data processing module of the system can also be configured to extract parameters related to the risk of complications, and the algorithm logic is to perform frequency domain analysis on the original optical signals detected by the in-vitro optical probe module, as the heartbeat-driven microvascular pulsation will superimpose a weak photoplethysmography (PPG) signal on the optical signal; the data processing module extracts a physiological indicator representing the local tissue blood perfusion state in a preset heart rate frequency range covering 0.8Hz to 2.5Hz through fast Fourier transform , which is defined as , wherein is the signal energy of the optical signal in the heart rate frequency range, and is the signal energy of the direct current component of the optical signal; when complications such as bacterial infection occur, the local tissue appears persistent blood perfusion enhancement due to inflammatory response, which is manifested as a persistent increase in the baseline of the physiological indicator ; the data processing module generates a complication risk warning based on the synergistic change between the acceleration of the calculated degradation rate and the persistent increase in the physiological indicator, and outputs a neutral risk parameter that needs to be further interpreted by professionals; another extended implementation is that the electromagnetic radiation emitted by the in-vitro optical probe module can be configured as broadband electromagnetic radiation covering the near-infrared band, and the data processing module performs water content analysis logic in parallel; based on the physical principle that water molecules have a characteristic absorption peak at about 970nm in the near-infrared band, the data processing module analyzes the signal intensity at the preset wavelength (970nm) related to the water molecule absorption characteristic in the broadband optical signal, and the signal intensity at a reference wavelength (850nm), and based on the ratio of the two The system determines an index characterizing the state of tissue edema in vivo by analyzing changes in the hydrogel's structure. Furthermore, to characterize the macroscopic structural integrity and mechanical properties of the hydrogel, the system can be configured to perform active mechanical property probing. This process responds to a standardized external mechanical disturbance applied to the in vivo region, for example, by an operator applying a preset pressure from 10 grams to 50 grams to the skin surface via an external optical probe module. Under this disturbance, the underlying hydrogel-tracer composite structure undergoes macroscopic deformation. This deformation alters the optical path length and scattering characteristics, inducing a transient response waveform in the optical signal synchronized with the mechanical disturbance. The data processing module detects and analyzes characteristics such as the amplitude and rate of change of this transient response waveform, and based on these characteristics, determines a mechanical index characterizing the structural integrity of the hydrogel-tracer composite structure, providing a physical dimension information orthogonal to chemical degradation for the assessment of the material's functional state.

[0031] Example 1: In a postoperative irregular wound filling application, an injectable hydrogel dressing containing tracer particles was used to monitor changes in the structural integrity of the dressing in vivo. Initially, conventional imaging analysis showed changes in the material volume at the implantation site, but it was impossible to distinguish whether this volume change was caused by the degradation and swelling of the material itself or by inflammatory edema of the surrounding tissue. This lacked direct physical quantity support for determining whether the material network structure remained intact. To obtain parameters directly related to the material network structure, the detection system of this invention was applied to this scenario. During the first measurement, the in vitro optical probe module was applied to the skin on the surface of the wound. The data processing module first executed a self-calibration procedure, which controlled the light-emitting diode in the probe to emit high-energy light pulses. Based on the transient optical response characteristics caused by the photothermal effect of the tracer particles, a baseline value characterizing the initial state of the hydrogel-tracer composite structure in vivo was determined. This step provides an in-vivo calibrated initial signal reference for all subsequent measurements. The system then switches to normal monitoring mode, periodically recording the optical signal. and based on the benchmark value The equivalent mass loss rate of the hydrogel was calculated.

[0032] After 48 hours of system operation, the equivalent mass loss rate calculated by the data processing module showed an unexpected acceleration. It should be noted that this single dimension of information is insufficient to determine whether the acceleration stemmed from individual metabolic differences or degradation caused by complications. At this point, another parallel analysis logic within the data processing module—frequency domain analysis of the same original optical signal—revealed a coordinated change. This analysis logic continuously tracked signal energy changes within the heart rate frequency range of 0.8 Hz to 2.5 Hz and calculated physiological indicators characterizing the local tissue blood perfusion status. Data shows that in the 12 hours prior to the acceleration of this equivalent mass loss rate, physiological indicators... The baseline has shown a continuous upward trend; the data processing module outputs a complication risk warning based on the established synergistic relationship between the accelerated degradation rate and the continuous increase in physiological indicators; this warning is not a clinical diagnosis, but a technical indicator at the material analysis level, which characterizes the correlation between the changes in the physicochemical state of the material and the changes in the physical state of its microenvironment; this information provides an objective data reference for subsequent intervention decisions before other signs appear. This approach transforms an analytical problem that originally relied on indirect morphological observation into a quantitative analysis process that can be cross-validated through the synergistic changes of two independent physical parameters.

[0033] Example 2: To verify the accuracy of the detection system of the present invention in quantifying the degradation rate of hydrogels, and to compare its performance with indirect measurement methods and systems lacking calibration, this example experiment was conducted. The purpose of the experiment was to simulate the material degradation process in an in vitro controlled environment and compare the equivalent mass loss rate output by the system with the actual mass loss of the material and conventional volume change indicators. The experimental platform consisted of a constant temperature water bath, an optical measurement system, and a reference data acquisition system. The constant temperature water bath was used to provide 37.0... The system provides a stable environment containing simulated bodily fluids with collagenase to degrade the hydrogel. The optical measurement system, which is the detection system of this invention, includes an external optical probe module containing a near-infrared light-emitting diode with a peak wavelength of 808 nm and a silicon photodiode with a sampling rate of 100 Hz. The reference data acquisition system includes an analytical balance with an accuracy of 0.1 mg, used to determine the actual mass loss of the hydrogel by freeze-drying and weighing, and a volume measurement device consisting of a 5-megapixel camera and image analysis software.

[0034] The preparation process of the test samples is as follows: silica microspheres with an average particle size of 500 nm were used as tracer particles and physically mixed with a gelatin-methacrylyl hydrogel precursor solution to form the test mixture; three sample groups were set up in the experiment, namely the sample group of the present invention, control group A, and control group B; wherein, during the preparation of the sample group of the present invention, the volume of each sample mixture fluctuated by 10% around 1.0 mL to simulate the dose difference in clinical injection operation; the preparation method of control group A was the same as that of the sample group of the present invention; control group B did not perform optical measurements, but was only used for the benchmark measurement of volume and actual mass; at the beginning of the experiment, all sample groups were placed in a constant temperature water bath; for the sample group of the present invention, at time 0, the system first executed the self-calibration procedure, and by applying a high-energy light pulse and analyzing the resulting transient optical response characteristics, independently determined the true initial state benchmark value for each sample. For control group A, the self-calibration procedure was not performed, and its data processing module used a fixed initial signal value based on the theoretical concentration for subsequent calculations. Subsequently, measurements were taken on each sample group at time points of 12h, 24h, 36h, 48h, 60h, 72h, 84h, and 96h. The sample group of this invention and control group A output the equivalent mass loss rate through their respective calculation methods. At each time point, one sample was taken from each sample group, and its true mass loss was determined by the freeze-drying and weighing method. At the same time, the sample of group B was photographed to calculate its volume change. The experimental data are recorded as shown in Table 1.

[0035] Table 1: A comparison table of measurement data for each sample group at different time points.

[0036] Time (h) Actual mass loss (%) Inventive sample group - calculated value (%) Control group A - calculated value (%) Control group B - volume change (%) 0 0.0 0.0 8.1 5.2 12 8.5 8.3 16.5 3.1 24 19.2 19.5 27.8 -2.5 36 31.8 31.5 40.2 -11.6 48 45.1 44.7 53.9 -22.8 60 58.6 59.1 67.8 -35.1 72 70.3 69.8 79.5 -46.7 84 81.2 81.9 90.1 -58.2 96 89.5 88.7 97.4 -69.4

[0037] Data analysis shows that the coefficient of determination for linear fitting between the calculated values ​​of the sample group of this invention and the actual mass loss values ​​measured by the freeze-drying weighing method over the entire monitoring period is... Greater than 0.99; Control group A, lacking in vivo calibration of the initial state, had an initial error at time 0 caused by sample dosage differences, and this error persisted in subsequent calculations; Volume change data of control group B showed that in the initial 0-12h degradation period, the sample volume increased due to water absorption and swelling, and this trend was opposite to the actual mass loss trend. The subsequent volume reduction rate was also not proportional to the mass loss rate, indicating that the indirect measurement method based on volume change lacked a direct correspondence between the measurement information and the integrity of the material network structure; Experimental results show that the detection system of this invention, by performing self-calibration of the initial state, can correct variables introduced by operation, providing a quantitative degradation rate analysis method directly related to the actual mass loss of the material. Its data accuracy is higher than that of systems lacking calibration and indirect measurement methods based on morphological changes.

[0038] Example 3: This example combines Figures 1 to 3 A description of a degradation rate detection system for injectable hydrogel wound dressings, such as... Figure 1As shown, the hydrogel tracer composite structure located in the in vivo environment serves as the core signal source. The release of its tracer is controlled by the dynamic changes in the pore size of the gel network. The external optical probe module of the external probe part emits probe light towards the implantation area and detects the returned optical signal caused by changes in tracer concentration. The data processing part first performs self-calibration before the monitoring task using the original optical signal through the in vivo self-calibration module. By emitting high-energy light pulses and analyzing transient optical responses, a benchmark value characterizing the true initial state is determined. Subsequently, in routine monitoring, the optical signal attenuation rate analysis module continuously calculates the attenuation rate of the optical signal over time based on the calibrated initial benchmark value and converts it into the equivalent mass loss rate of the material, thereby obtaining a quantitative hydrogel degradation rate directly related to the structural integrity of the material. At the same time, the complication risk warning analysis module performs frequency domain analysis on the original optical signal, extracts the energy in the heart rate frequency range as a physiological indicator, and analyzes the synergistic change between the continuous increase of this indicator and the accelerated degradation rate, ultimately generating the analysis result of complication risk warning.

[0039] like Figure 2 As shown, after the system starts up, it first enters a standby / ready state, waiting for the operator to issue a start monitoring command. Upon receiving the command, the system enters an in vivo self-calibration state, performing high-energy light pulse emission and transient response analysis to establish a measurement benchmark. Once calibration is complete and a true initial benchmark is obtained, the system automatically switches to a regular monitoring state. In this state, the system initiates low-power periodic detection and continuously collects optical signals to analyze degradation rates and physiological indicators. If preset risk conditions of accelerated degradation and continuously rising physiological indicators are detected, the system transitions from the regular monitoring state to a complication risk warning state and issues a warning signal to the user. This warning state will return to the regular monitoring state after the risk conditions disappear or the operator confirms. Regardless of whether the system is in a regular monitoring or risk warning state, once it receives a stop monitoring command from the operator, the system will terminate the current task.

[0040] like Figure 3As shown, the flow is completed by five logical units of monitoring system, degradation rate analysis, blood perfusion analysis, risk assessment and early warning output in cooperation, wherein the monitoring system first transmits the optical signal to the degradation rate analysis unit, the unit compares the current rate with the 24-hour average value after calculating the current rate, and if the condition is met, the rate acceleration state signal is sent to the risk assessment unit, at the same time, the monitoring system transmits the PPG signal to the blood perfusion analysis unit, the unit calculates the physiological index through frequency domain analysis and compares it with the baseline value, if the condition is met, the perfusion enhancement state signal is sent to the risk assessment unit, the risk assessment unit enters the judgment process after receiving the above two state signals, only when the condition of double abnormality lasting for 6 hours is met, the cooperative change is confirmed and the risk warning instruction is generated to the early warning output unit, finally the early warning signal is outputted by the early warning output unit, then the system returns and continues regular monitoring, if the double abnormality condition is not met, the system directly maintains the normal state and continues regular monitoring.

[0041] Embodiment 4: In order to ensure that the analysis results outputted by the system of the present application have consistency and comparability when applied to different formula hydrogel materials and different individual tissue conditions, a set of standardized offline calibration and model establishment procedures need to be performed; the purpose of the procedure is to provide determined parameters for the data processing model built in the system under controllable conditions in vitro, so as to associate the original physical signal with the specific physical state of the material to be tested; the calibration procedure is performed on an experimental platform composed of a tissue simulation phantom and a standard mechanical test; first, in order to establish a photoacoustic signal feature model for discriminating the physical state of tracer particles, three groups of samples need to be prepared: the first group is to physically imprison tracer particles in undegraded hydrogel network, representing the imprisoned state; the second group is to suspend the same kind of tracer particles in simulated body fluid, representing the released state outside the network; the third group is to prepare samples after co-culturing the tracer particles with macrophages, representing the state after being phagocytosed by cells; then, the in vitro optical probe module of the present application containing an ultrasonic transducer is used to excite and receive the three groups of samples respectively to obtain their respective photoacoustic signals.

[0042] The data processing module processes the collected photoacoustic signals of each group, and the algorithm path is as follows: first, Fourier transform is performed on the time domain waveform of each photoacoustic signal to obtain its corresponding frequency spectrum; second, two characteristic parameters of peak amplitude and energy centroid frequency are extracted from the frequency spectrum; by statistically analyzing the data of the three groups of samples, a state classification rule is established, and when a photoacoustic signal meets the condition of peak amplitude greater than a preset amplitude threshold and energy centroid frequency greater than a preset frequency threshold , the tracer particles corresponding to the photoacoustic signal are determined to be in the imprisoned state; the threshold here is determined by statistical analysis of the data of the three groups of samples is the classification boundary parameter obtained by training the calibration dataset with the support vector machine (SVM) classification algorithm, and the procedure converts the state discrimination problem into a classification process based on objective measurement and statistical model; secondly, to determine the calculation parameters of the mechanical index representing the structural integrity of the hydrogel, the correlation with the mechanical properties of the material needs to be established; the process first prepares a series of hydrogel samples at different degradation levels, i.e. the actual mass loss is 0%, 20%, 40%, 60%, and 80%, respectively, and measures and records the corresponding storage modulus of each sample as the reference value of its structural integrity; then, the standardized external mechanical disturbance of the present application is performed on each sample, and the transient response waveform of the optical signal under this disturbance is recorded; the data processing module extracts the maximum change amplitude and the rising slope of the two features from the waveform; through the multivariate linear regression analysis of all sample data pairs, the weight coefficient in the calculation formula can be determined; and ; it should be noted that the mechanical index here is different from the unit of the storage modulus , but through the regression calibration, a mapping relationship between the two is established; after completing the above procedure, the classification threshold for state discrimination and the weight coefficient for calculating the mechanical index in the data processing module are determined; after the calibration process of any detection system, the subsequent degradation rate output in the normal monitoring mode is corrected after the photoacoustic signal correction, which can correct the interference of factors such as pseudo-release and pseudo-aggregation, and the output mechanical index also establishes a correlation with the actual mechanical properties of the material, so that the comprehensive analysis of the material state is based on a traceable calibrated data model.

[0043] Example 5: Before applying the detection system of the present application to a new hydrogel material formula, an offline calibration procedure needs to be performed to establish a quantitative calibration model between the optical signal decay rate and the equivalent mass loss rate of the specific material; the procedure prepares multiple groups of new formula hydrogel samples containing tracer particles, and places them in an accelerated degradation environment in vitro; at multiple preset time points, the optical signal decay rate of the system is measured , and the actual mass loss rate is measured by the freeze-drying weighing method , so as to obtain a series of data pairs , and through polynomial regression fitting of these data pairs, the functional relationship , and the fitting coefficients of the function relationship constitute a preset calibration model, and are stored in the data processing module in association with an identifier of the specific hydrogel material formula.

[0044] Correspondingly, before performing a routine monitoring task on a specific monitoring target, a field baseline determination procedure needs to be performed to correct the influence of individual tissue optical properties on the measurement of the tissue edema state indicator; in the procedure, before the routine monitoring on the hydrogel-tracer composite structure starts, the operator places the extracorporeal optical probe module on a healthy tissue region adjacent to the monitoring target and not affected by trauma, the system performs a measurement using broadband electromagnetic radiation, and calculates the water absorption index of the healthy tissue ; the measurement value is stored by the data processing module as the personalized baseline value of the monitoring target In subsequent routine monitoring, the tissue edema state indicator reported by the system is the difference between the currently measured water absorption index and the baseline value , thereby providing a differential measurement result that has been normalized against the individual baseline.

[0045] Embodiment 6: In order to make the dual-peak sequential release tracer system have optimal time separation between the early and late stages of signals when analyzing the degradation process of a specific hydrogel, an offline optimization parameter search procedure needs to be performed; the procedure first determines the half-life of the target hydrogel material in a preset degradation environment, i.e. the time when the mass loss reaches 50% through in vitro degradation experiments ; accordingly, multiple batches of degradable microspheres encapsulating the tracer particles are prepared, each batch of microspheres using a polylactic acid-glycolic acid copolymer material with a different molecular weight or monomer ratio, and the half-life of each batch of microspheres is determined through in vitro release experiments ; finally, the batch of microspheres whose half-life is closest to the half-life of the target hydrogel is selected as the combination that achieves the optimization goal.

[0046] In order to establish the baseline reference model and the quantitative judgment basis for abnormal states relied on by the complication risk early warning function, the data processing module is configured to perform the following judgment procedure: first, compare the currently measured equivalent mass loss rate with the sliding average value of the rate 24 hours ago, and when is greater than 1.5 times the average value, it is determined that the degradation process enters an accelerated state; secondly, compare the currently measured physiological indicator The 12-hour moving average value is compared with the initial 24-hour baseline value, and when the average value continuously exceeds 1.2 times the baseline value, it is determined that the local blood perfusion enters a continuously enhanced state; only when the degradation acceleration state and the continuously enhanced blood perfusion state appear simultaneously, and the duration of the double state exceeds 6 hours, the data processing module of the system finally outputs the complication risk warning.

[0047] It is obvious to those skilled in the art that the present application is not limited to the details of the above exemplary embodiments, and the present application can be implemented in other specific forms without departing from the spirit or essential characteristics of the present application.

[0048] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application and are not limiting. Although the present application has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solutions of the present application can be modified or replaced equivalently without departing from the spirit and scope of the technical solutions of the present application.

Claims

1. An injectable hydrogel wound dressing degradation rate detection system, characterized in that, The system comprises: a hydrogel-tracer composite structure formed by in vivo solidification of a physically mixed injectable hydrogel precursor and tracer particles, the tracer particles having a particle size and the hydrogel network having a pore size dynamically evolving during degradation, the particle size and the pore size being set to have a preset physical critical size correspondence, which makes the tracer particles only change from a physically trapped state to a releasable state when the pore size evolves to a critical size larger than the particle size; an in vitro optical probe module configured to emit electromagnetic radiation of a predetermined wavelength to an in vivo region implanted with the hydrogel-tracer composite structure, and to detect an optical signal caused by a change in the concentration of the tracer particles; a data processing module configured to: first execute a self-calibration mode, in which the in vitro optical probe module is controlled to emit high-energy light pulses, and determine a reference value representing a real initial state of the hydrogel-tracer composite structure in vivo based on a transient optical response feature caused by a photothermal effect of the tracer particles; and then execute a regular monitoring mode, in which the decay rate of the optical signal over time is determined based on the reference value of the real initial state, and the decay rate is processed as a degradation rate of the hydrogel; the tracer particles comprise at least two tracer components having different release kinetics, wherein a first tracer component is a free-state tracer particle, and a second tracer component is a slow-release-state tracer particle encapsulated in a degradable microsphere; and the data processing module is further configured to analyze a bi-phasic decay curve of the optical signal change formed by sequential release of the at least two tracer components. And, the system quickly and non-invasively acquires the effective optical attenuation coefficient of the overlying tissue at the current implantation point by means of spatially resolved diffuse reflectance measurement before emitting the high-energy light pulse , then obtains the transient optical response characteristic value by means of high-energy light pulse excitation , and finally substitutes the in-situ measured data into a calibration model to solve the real initial state reference value corrected by individualized tissue characteristics , ;​ wherein the calibration model is established according to the following procedure: in the offline calibration stage, a series of tissue phantoms with different and known effective optical attenuation coefficients are used, under each specific tissue phantom, a plurality of groups of hydrogel samples with different known tracer concentrations are prepared and measured, and their transient optical response characteristic values S are recorded, thereby obtaining a three-dimensional data set containing , , , wherein is the true concentration of the tracer particles; The data set is fitted by using response surface methodology and other multivariate regression analysis techniques to establish a calibration model .

2. The injectable hydrogel wound dressing degradation rate detection system of claim 1, wherein, The data processing module is further configured to perform frequency domain analysis on the optical signal detected by the extracorporeal optical probe module to extract a physiological indicator representing local tissue blood perfusion status in a preset heart rate frequency range covering 0.8 Hz to 2.5 Hz wherein, wherein, is a signal energy of the optical signal in the heart rate frequency range, is a signal energy of a direct current component of the optical signal; and based on a synergistic change between the acceleration of the degradation rate and the sustained increase of the physiological indicator, generating a complication risk warning.

3. The injectable hydrogel wound dressing degradation rate detection system of claim 1, wherein, The in vitro optical probe module further comprises an ultrasonic transducer coaxially integrated with the electromagnetic radiation emission source; and the data processing module is further configured to control the in vitro optical probe module to emit nanosecond-level pulsed light to excite a photoacoustic signal at the tracer particles, receive the photoacoustic signal through the ultrasonic transducer, and identify whether the tracer particles are in a trapped state within the hydrogel network or in a released state outside the network based on the amplitude and spectral features of the photoacoustic signal, and then correct the determined degradation rate of the hydrogel based on the identification result.

4. The injectable hydrogel wound dressing degradation rate detection system of claim 1, wherein, The system is further configured to detect and analyze a transient response waveform related to the macroscopic deformation of the hydrogel-tracer composite structure caused by a mechanical disturbance on the in vivo region, and determine a mechanical indicator representing the structural integrity of the hydrogel-tracer composite structure based on the amplitude and change rate features of the transient response waveform.

5. The injectable hydrogel wound dressing degradation rate detection system of claim 1, wherein, The electromagnetic radiation emitted by the in vitro optical probe module is broadband electromagnetic radiation covering the near-infrared band; and the data processing module is further configured to analyze the signal intensity at a preset wavelength related to the absorption feature of water molecules and the signal intensity at a reference wavelength in the optical signal, and determine an indicator representing the tissue edema state of the in vivo region based on the change in the ratio of the two.

6. The injectable hydrogel wound dressing degradation rate detection system of claim 1, wherein, The tracer particles are biocompatible inert particles having near-infrared absorption or scattering properties.

7. The injectable hydrogel wound dressing degradation rate detection system of claim 1, wherein, ​ 8. The injectable hydrogel wound dressing degradation rate detection system of claim 1, wherein, The in-vitro optical probe module comprises a light emitting diode for emitting electromagnetic radiation, and a photodiode for detecting optical signals.

9. The injectable hydrogel wound dressing degradation rate detection system of claim 1, wherein, The transient optical response is characterized by a fluctuation echo of the backscattered light signal following a high-energy light pulse, due to a transient thermoelastic deformation of the micro-environment around the tracer particles.

10. The injectable hydrogel wound dressing degradation rate detection system of claim 1, wherein, The data processing module is further configured to convert the decay rate of the optical signal into an equivalent mass loss rate of the hydrogel by a preset calibration model.

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