Blood detection method and system for compatibility of degradation products of implanted medical device

Abstract

The invention discloses a blood detection method and system for compatibility of degradation products of an implanted medical device, and relates to the technical field of biocompatibility evaluation of the implanted medical device, and the method comprises the following steps: obtaining a degradation product solution subjected to solid-liquid separation and gradient dilution treatment; and preparing a pretreated blood sample. A pretreated blood sample and degradation product solutions with different concentrations are mixed according to a set proportion, reaction treatment is completed under the controlled temperature and time conditions, and then reaction system supernate is obtained through termination and separation operation. Blood chemical indexes are detected, an allowable fluctuation threshold value is determined based on blank control statistics, and the relative offset, the standard exceeding degree and the compatibility index of aggregation output of all the indexes are calculated. And finally, carrying out unified recording, contrast arrangement and structured output on detection results under different concentration conditions. The quantitative characterization of the influence of the degradation product on the blood chemical system can be realized under the same detection framework, and the comparability and repeatability of the detection result are improved.

Description

Technical Field

[0001] This invention relates to the field of biocompatibility evaluation technology for implantable medical devices, specifically to a blood testing method and system for the compatibility of degradation products of implantable medical devices. Background Technology

[0002] With the rapid development of biomedical materials and implantable medical device technology, biodegradable metals, biodegradable polymers, and their composite materials are widely used in orthopedics, cardiovascular medicine, and nerve repair. These implantable medical devices undergo varying degrees of degradation during their service in the body, and their degradation products may enter the circulatory system, interacting with blood components in complex chemical or biological ways. Therefore, the evaluation techniques for the biocompatibility of implantable medical device materials have gradually expanded from traditional cytotoxicity and tissue compatibility testing to a systematic analysis of blood compatibility and blood chemical reactions. In existing research, blood testing methods mainly rely on blood biochemical indicators, inflammatory factors, or coagulation parameters to qualitatively or semi-quantitatively assess the interaction between the material or its extract and blood, providing fundamental data support for the safety evaluation of implantable medical devices.

[0003] Although existing blood testing technologies have been used for biocompatibility evaluation of implantable medical devices, they still have significant shortcomings in analyzing the blood compatibility of degradation products from these devices. First, existing technologies often use material extracts or single leachates as the detection targets, failing to accurately reflect the multi-component, dynamically changing degradation product system formed by the gradual degradation of implantable medical devices under physiological conditions in vivo. This leads to discrepancies between test results and the actual in vivo environment. Second, existing blood testing methods typically rely on absolute detection values ​​or single thresholds of blood chemical indicators, failing to fully consider individual differences in blood samples and natural fluctuations during the testing process. This results in poor comparability between different batches of tests and makes it difficult to accurately distinguish between abnormal changes and normal fluctuations caused by degradation products. Third, existing technologies often focus on single or a few blood indicators, lacking a systematic characterization of the synergistic changes of multiple indicators, making it difficult to reflect the comprehensive impact of degradation products on the blood system from a holistic perspective. Furthermore, current result processing methods often remain at the stage of simple recording or qualitative evaluation, lacking a unified data processing and structured output mechanism, which is not conducive to comparative analysis of test results under different degradation conditions and concentration levels. For the reasons mentioned above, existing technologies are unable to achieve precise, quantitative, and repeatable evaluation of the blood compatibility of degradation products from implanted medical devices, and are also unable to obtain stable and reliable test results. Summary of the Invention

[0004] In view of the above-mentioned problems, the present invention is proposed.

[0005] Therefore, the technical problem solved by the present invention is that existing methods for detecting the blood compatibility of implantable medical devices have problems such as mismatch between the test object and the actual in vivo degradation process, difficulty in eliminating the influence of natural blood fluctuations based on absolute test values, lack of unified quantitative characterization methods for multiple blood chemical indicators, and how to achieve stable, comparable and quantitative detection of the blood compatibility of degradation products of implantable medical devices.

[0006] To address the aforementioned technical problems, this invention provides the following technical solution: a blood testing method for the compatibility of degradation products from implantable medical devices, comprising: cleaning and drying materials identical to the actual implantable medical device, and subjecting them to controlled degradation in a buffer solution under physiological conditions to obtain a solution of degradation products from the implantable medical device after solid-liquid separation and gradient dilution; preparing pretreated blood samples by aseptic collection, anticoagulation treatment, centrifugation, and isotonic environment adjustment; mixing the pretreated blood samples with degradation product solutions of different concentrations in a set ratio, and completing the reaction treatment under controlled temperature and time conditions; subsequently obtaining the supernatant of the reaction system for detection through termination and separation operations; detecting blood chemical indicators in the supernatant of the reaction system, and determining the allowable fluctuation threshold based on blank control statistics, calculating the relative offset, exceedance degree, and compatibility index of each indicator; uniformly recording, comparing, and structurally outputting the blood chemical detection values, threshold parameters, and compatibility index obtained under different degradation product concentration conditions, and outputting the detection result dataset.

[0007] As a preferred embodiment of the blood testing method for compatibility of degradation products of implantable medical devices described in this invention, the controlled degradation under physiological conditions in a buffer solution includes selecting materials consistent with the actual implantable medical device in terms of material composition and manufacturing process as the treatment object, cleaning and drying the materials, and then immersing them in a buffer solution with ionic composition matching the body fluid environment and pH within the physiological range, allowing the materials to undergo natural degradation under in vivo conditions; no additional chemical catalysts or external reaction-promoting conditions are introduced during the degradation process; after the degradation treatment is completed, the buffer solution is subjected to solid-liquid separation, retaining only the degradation product components in the dissolved state, and the obtained degradation product solution is subjected to multi-level concentration treatment.

[0008] As a preferred embodiment of the blood testing method for compatibility of degradation products of implantable medical devices according to the present invention, the preparation of pretreated blood samples includes: collecting blood samples under sterile conditions and performing anticoagulation treatment; centrifuging the anticoagulated blood samples to obtain plasma or serum components; adjusting the environment of the blood samples with an isotonic solution of the same composition as the buffer solution used for the degradation product solution, so that different blood samples are consistent in ion composition and osmotic pressure conditions; and equilibrating the environmentally adjusted blood samples under controlled temperature conditions.

[0009] As a preferred embodiment of the blood testing method for compatibility of degradation products of implantable medical devices according to the present invention, the step of obtaining the supernatant of the reaction system for testing through termination and separation operations includes mixing pretreated blood samples with degradation product solutions of different concentration gradients in a predetermined ratio, so that the blood samples maintain a certain volume fraction in the reaction system; the mixed reaction system is subjected to reaction treatment under controlled temperature and time conditions, the system is kept closed during the reaction, and no sampling or liquid replenishment is performed; after the reaction is completed, the reaction is terminated by lowering the system temperature, and the reaction system is separated.

[0010] As a preferred embodiment of the blood testing method for compatibility of degradation products of implantable medical devices described in this invention, the blood chemical indicators in the supernatant of the reaction system are detected by comparing the test results of the reaction system sample containing degradation products with the test results of the blank control reaction system sample to obtain the degree of change of each blood chemical indicator relative to the blank control; the natural fluctuation range of the blank control reaction system sample under repeated testing conditions is used as a reference baseline, so that the evaluation of changes in blood chemical indicators is based on comparative statistics.

[0011] As a preferred embodiment of the blood testing method for compatibility of degradation products of implantable medical devices according to the present invention, the step of determining the allowable fluctuation threshold based on blank control statistics and calculating the relative offset, degree of exceeding the standard, and compatibility index of each indicator includes, when evaluating the changes of each blood chemical indicator, if the degree of change of the blood chemical indicator relative to the blank control exceeds the natural fluctuation range of the indicator under blank conditions, the excess part is recorded as the effective perturbation contribution of the indicator; if the degree of change does not exceed the natural fluctuation range, the indicator is not included in the calculation of the overall blood chemical perturbation level.

[0012] As a preferred embodiment of the blood detection method for compatibility of degradation products of implantable medical devices according to the present invention, the following steps are included: determining the allowable fluctuation threshold based on blank control statistics, calculating the relative offset, exceedance degree, and aggregated compatibility index of each indicator, including summarizing the perturbation contributions of each indicator when performing aggregated processing on the effective perturbation contributions of blood chemical indicators; and outputting a compatibility index to characterize the overall perturbation degree of blood chemistry under different degradation product concentration conditions through aggregated processing.

[0013] Another objective of this invention is to provide a blood testing system for the compatibility of degradation products of implantable medical devices. This system can detect blood chemical indicators in the supernatant of the reaction system, determine the allowable fluctuation threshold based on blank control statistics, calculate the relative deviation, degree of exceedance, and compatibility index of each indicator, and solve the problem that current blood compatibility testing methods for implantable medical devices lack a unified quantitative characterization method for multiple blood chemical indicators.

[0014] As a preferred embodiment of the blood testing system for the biocompatibility of degradation products of implantable medical devices according to the present invention, the system includes: a sample preparation module, a reaction construction module, and a detection quantification module. The sample preparation module is used to prepare the test object, including controlled degradation of a material identical to the actual implantable medical device to obtain a degradation product solution, and collecting, anticoagulating, separating, and environmentally adjusting blood samples to form a basic sample. The reaction construction module is used to mix the pretreated blood sample with degradation product solutions of different concentrations under controlled conditions and complete the reaction process to obtain a reaction system sample. The detection quantification module is used to detect blood chemical indicators in the reaction system sample, and quantify the detection results based on blank control statistics, outputting detection results characterizing the blood biocompatibility of the degradation products.

[0015] A computer device includes a memory and a processor, the memory storing a computer program, the processor executing the computer program to implement steps of a blood testing method for compatibility with degradation products of implantable medical devices.

[0016] A computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the steps of a blood testing method for compatibility with degradation products of implantable medical devices.

[0017] The beneficial effects of this invention are as follows: The blood detection method for compatibility of degradation products of implantable medical devices provided by this invention achieves systematic and quantitative characterization of the interaction process between degradation products and the blood system. First, by cleaning and drying materials identical to those used in actual implantable medical devices, and then subjecting them to controlled degradation in a buffer solution under physiological conditions, a degradation product solution after solid-liquid separation and gradient dilution is obtained. This ensures the consistency of the degradation product composition with the actual in vivo degradation environment from the material source, thus avoiding the insufficient representativeness caused by the use of artificial simulants or single chemical components in traditional methods. Second, by aseptically collecting, anticoagulating, centrifuging, and adjusting the isotonic environment of blood samples, pretreated blood samples are prepared, ensuring that different blood samples are in a consistent physicochemical state before the reaction, reducing the interference of individual differences and operational fluctuations on the detection results. Furthermore, the pretreated blood samples are mixed with degradation product solutions of different concentrations in a set ratio, and the reaction is completed under controlled temperature and time conditions. Combined with termination and separation operations, the supernatant of the reaction system is obtained, thereby achieving a controllable construction of the relationship between degradation product concentration and blood chemical response. Finally, by detecting multiple blood chemical indicators in the supernatant of the reaction system and determining the allowable fluctuation threshold based on blank control statistics, only changes exceeding the natural fluctuation range are included in the overall evaluation. A compatibility index is then output through multi-indicator aggregation, ensuring that the test results accurately reflect the degree of blood chemical disturbance caused by degradation products. Through the synergistic cooperation of the above steps, this invention avoids the biases caused by relying solely on a single indicator or absolute value in existing technologies, improving the stability, repeatability, and objectivity of blood compatibility test results. Attached Figure Description

[0018] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 The flowchart below shows the overall process of a blood testing method for compatibility with degradation products of implantable medical devices, as provided in the first embodiment of the present invention. Detailed Implementation

[0020] To make the above-mentioned objects, features, and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the protection scope of the present invention.

[0021] Example 1, referring to Figure 1 As one embodiment of the present invention, a blood testing method for compatibility with degradation products of implantable medical devices is provided, comprising: S1: By cleaning and drying materials identical to those used in actual implanted medical devices, and then subjecting them to controlled degradation in a buffer solution under physiological conditions, a solution of implanted medical device degradation products after solid-liquid separation and gradient dilution is obtained. Blood samples are then aseptically collected, anticoagulated, centrifuged, and subjected to isotonic environment adjustment to prepare pretreated blood samples.

[0022] Furthermore, material samples identical to those used in actual implanted medical devices were selected as the degradation treatment targets, with the materials originating from the same production process or equivalent batches. The materials were cut to ensure each sample had a substantially uniform exposed surface area, avoiding heat treatment or chemical modification during the cutting process. The cut materials were then sequentially cleaned with deionized water and organic solvents, with each cleaning medium lasting at least 5 minutes, to remove soluble residues from the material surface. After cleaning, the materials were dried under controlled temperature conditions of 30–40°C until no visible liquid residue remained on the surface.

[0023] After material pretreatment, a buffer solution was prepared to simulate the in vivo degradation environment. The buffer solution was a phosphate-buffered saline solution, whose ionic composition matched the body fluid environment, and the pH was controlled within the physiological range of 7.2–7.4 through acid-base adjustment. Before use, the buffer solution was filtered through 0.22 μm micropores and sterilized to avoid interference from exogenous particles and microorganisms on the degradation process. The source of the buffer solution used in the same batch of tests remained consistent.

[0024] The treated material sample was placed in a sealed container, and the buffer solution was added according to a preset mass-to-volume ratio to completely submerge the material in the solution. The mass-to-volume ratio was controlled within the range of 0.05–0.20 g / mL. The sealed container was then placed under constant temperature conditions for immersion treatment, with the immersion temperature controlled within the range of 36–38°C, and the degradation treatment time set to be no less than 48 hours. No additional chemical catalysts or strong mechanical shear conditions were introduced during the degradation process; only the natural convection state of the buffer solution was maintained.

[0025] It should be noted that after the degradation treatment, the resulting solution was sampled and solid-liquid separation was performed. Sampling was carried out under aseptic conditions, and the extracted solution was centrifuged to remove undissolved material residues. The centrifugation conditions were controlled at 3000–5000 g for 5–15 min. Subsequently, the supernatant was filtered with a pore size of 0.22 μm to obtain a clear degradation product solution.

[0026] The obtained degradation product solution was serially diluted according to a preset ratio to form at least three solutions with different concentration levels. The dilution solutions had the same composition as the degradation buffer solution. After dilution, the solutions were allowed to stand at 35–37°C for at least 20 minutes to ensure that the solution composition was uniform and stable.

[0027] The treated degradation product solution is temporarily stored before entering the blood test, with the storage temperature controlled at 2–8°C and the storage time not exceeding 24 hours. Simultaneously, a buffer solution free of the material is prepared following the same filtration, temperature control, and temporary storage process as described above, serving as a blank control sample for the blood test.

[0028] Furthermore, after preparing the degradation product solution of the implanted medical device, blood samples are collected and pretreated. The blood samples are selected from donor samples from the same batch. Disposable sterile blood collection instruments are used during collection, and an anticoagulant is added immediately after collection to prevent blood aggregation during processing. The amount of anticoagulant added is controlled according to the blood volume ratio to keep the blood sample in a liquid state without altering its original chemical composition.

[0029] After anticoagulation, blood samples were briefly placed at a controlled temperature to allow for overall stabilization. The samples were then separated into plasma or serum components by centrifugation at 1500–3000 g for 10–15 minutes. After separation, the supernatant was carefully aspirated, taking care not to disturb the cell deposits.

[0030] The obtained plasma or serum samples are pretreated and adjusted according to the consistency requirements of the tests. No chemical reagents or modifiers are introduced during pretreatment; the sample volume and ionic environment are standardized solely through mixing with an isotonic buffer solution. The composition of the isotonic buffer solution is consistent with that of the buffer solution used to simulate the in vivo degradation environment to ensure the comparability of blood reaction conditions. The mixing ratio is controlled according to the sample volume to maintain stability in osmotic pressure and ionic composition of the pretreated blood sample.

[0031] After adjusting the volume and environment, the blood samples were subjected to temperature equilibration. The blood samples were allowed to stand at 35–37°C for at least 15 minutes to ensure the sample temperature matched the reaction conditions, thus preventing temperature differences from affecting the chemical state of the blood. No stirring or vigorous shaking was performed during the temperature equilibration process; the samples were simply kept in a static state.

[0032] Pre-treated blood samples were aliquoted into predetermined volumes using aseptic techniques, with volume errors for each aliquot controlled within acceptable limits. The aliquoted blood samples were then temporarily stored at 2–8°C for no more than 12 hours before proceeding to the next reaction step; samples exceeding this storage time were discarded. Simultaneously, blank blood control samples were prepared following the same collection, anticoagulation, centrifugation, and pre-treatment procedures. These blank blood control samples, along with a prepared buffer solution free of materials, served as controls.

[0033] S2: The pretreated blood sample is mixed with degradation product solutions of different concentrations in a set ratio, and the reaction is completed under controlled temperature and time conditions. Then, the supernatant of the reaction system for detection is obtained through termination and separation operations.

[0034] Furthermore, after preparing the degradation product solution of the implanted medical device and collecting and pretreating the blood sample, a reaction process is performed between the blood sample and the degradation product solution. The reaction process is carried out under aseptic conditions, using disposable sterile reaction tubes or sterilized sealed containers. The reaction containers are kept dry before use to avoid introducing additional chemical components.

[0035] The pretreated blood sample was mixed with the obtained degradation product solution at a predetermined volume ratio. The mixing ratio was controlled within the range of 1:(0.1 to 1), that is, 0.1 to 1 volume of degradation product solution was added to each blood sample, so that the blood sample still maintained its major volume fraction in the reaction system. The mixing process was carried out by slow pipetting to avoid generating bubbles or violently disturbing the blood sample.

[0036] The mixed reaction system was subjected to reaction treatment under controlled temperature conditions. The reaction temperature was controlled within the range of 35–37°C, and the reaction system was kept in a static state under these conditions without high-speed shaking or forced mixing. Only slight inversion was performed in the initial stage of mixing to ensure the system homogeneity. The reaction duration was set to 30–120 min, and no sampling or liquid replenishment was performed during the reaction.

[0037] During the reaction process, the blood sample and the degradation product solution interact in a closed system. The reaction system is kept closed during the reaction to prevent external air ingress or solution evaporation from affecting its composition. For degradation product solutions of different concentration gradients, separate reaction systems were constructed with equal volumes of blood samples, and each system was processed simultaneously under the same temperature and time conditions.

[0038] It should be noted that the reaction system was terminated immediately after the reaction treatment was completed. Termination was achieved by transferring the reaction system from the reaction temperature environment to a temperature of 2–8°C, causing the overall temperature of the reaction system to drop rapidly. After termination, the reaction system was allowed to stand at low temperature for at least 10 minutes to stabilize its state.

[0039] The reaction system, after completing the reaction termination process, undergoes separation treatment according to the requirements of blood chemistry testing. Separation is performed by centrifugation at 1500–3000 g for 5–10 min to obtain the supernatant components for detection. Disturbing the sediment layer is avoided during separation, and the resulting supernatant serves as the test sample for blood chemistry indicators. Simultaneously, following the same mixing, reaction, termination, and separation procedure as described above, a prepared blank blood control sample is reacted with a prepared buffer solution containing no materials; the resulting sample serves as the corresponding blank control.

[0040] S3: Detect blood chemical indicators in the supernatant of the reaction system, determine the allowable fluctuation threshold based on the blank control statistics, and calculate the relative deviation, degree of exceedance, and compatibility index of each indicator and the polymer output.

[0041] Furthermore, after completing the reaction treatment of the blood sample with the degradation product solution and obtaining the supernatant to be tested, the blood chemical indicators in the supernatant are detected. The detection operation is performed in an experimental environment that meets the requirements for blood chemical analysis, using the same detection equipment and reagent conditions as described above to ensure comparability of detection conditions between different samples. The selected blood chemical indicators are quantitative indicators that can reflect changes in the chemical state of the blood system, and all indicators are detected using the same detection method in the same batch of tests.

[0042] For each sample of the reaction system, the first step was to detect... The measured values ​​of the blood chemical indicators are denoted as follows: Simultaneously, the blank control reaction system samples prepared according to the described procedure were simultaneously detected to obtain the corresponding blank control detection values, denoted as... All test values ​​are recorded as data directly output by the instrument, without manual correction.

[0043] After obtaining the test values, the standardized offset of the test results for each blood chemical indicator is calculated. For the first... The relative offset of each blood chemical indicator is expressed as follows:

[0044] in, Indicates the relative offset. To avoid positive numbers with excessively small denominators, the value is determined by the minimum resolution of the detection instrument used and remains consistent across the same batch of tests. Through the above calculations, the test results of each blood chemical indicator are uniformly converted into an expression of offset relative to the blank control.

[0045] Before determining the degree of exceedance, the permissible fluctuation thresholds for each blood chemical indicator are first determined. These permissible fluctuation thresholds are obtained based on the statistical distribution of the blank control reaction system samples. Specifically, multiple blank control reaction system samples are prepared under conditions where no degradation product solution is added, following a completely consistent mixing, reaction, termination, and separation process. The permissible fluctuation thresholds for the blank control reaction system samples are then analyzed. The test results of several blood chemical indicators were statistically analyzed to obtain the average level and natural fluctuation range of each indicator under blank conditions. Based on the statistical results, the relative fluctuation range of the indicator under blank conditions was taken as the allowable fluctuation range, and the corresponding allowable fluctuation threshold was determined accordingly. Within the same batch of tests, the permissible fluctuation thresholds for each blood chemical indicator remain fixed and do not change with a single sample.

[0046] After determining the allowable fluctuation threshold, the degree of exceedance of the relative deviation of each blood chemical indicator is calculated. For the first... The degree to which a blood chemical indicator exceeds the standard is determined according to the following formula:

[0047] in, Indicates the first The degree to which several blood chemical indicators exceed the standard.

[0048] After obtaining the exceedance levels of various blood chemical indicators, the exceedance levels of multiple blood chemical indicators are aggregated to obtain a compatibility index characterizing the overall perturbation level of blood chemistry. The compatibility index is expressed as:

[0049] in, The number of blood chemical indicators involved in the test. This represents the compatibility index, which is obtained by aggregating the levels of exceedance of multiple blood chemical indicators. The compatibility index is obtained by summing the exceedance levels of each indicator and then performing logarithmic processing. It is output as a continuous numerical value, serving as the blood chemical test result for the sample in this reaction system.

[0050] S4: Record, compare, and structure the blood chemical test values, threshold parameters, and compatibility indices obtained under different degradation product concentration conditions, and output the test result dataset.

[0051] Furthermore, after completing the detection of blood chemistry indicators, determining the allowable fluctuation thresholds, and calculating the compatibility index, the detection results corresponding to the samples of each reaction system are uniformly recorded and organized. The recorded content includes: the detection values ​​of each blood chemistry indicator in the reaction system samples, the detection values ​​in the corresponding blank control reaction system samples, the determined allowable fluctuation thresholds, relative deviations, the degree of exceeding the standard, and the compatibility index obtained by aggregating the degree of exceeding the standard of multiple blood chemistry indicators.

[0052] When processing the results, corresponding data record entries were established for degradation product solutions with different concentration gradients, ensuring that each record clearly corresponds to the specific concentration conditions of the prepared degradation product solution and the specific reaction system constructed. For multiple parallel samples obtained under the same degradation product solution conditions, their test results were recorded independently, with the sample number and batch information marked in the record.

[0053] After completing the single-sample recording, the results of multiple reaction system samples under the same degradation product solution conditions were compared and compiled. The detection values, relative offsets, exceedance levels, and compatibility indices of each blood chemical indicator were summarized and arranged according to a unified data format, enabling horizontal comparison of detection results between different samples within the same indicator dimension. This compilation process only involves data summarization and format standardization; no threshold judgments or classifications are performed on the original detection results or calculation results.

[0054] It should be noted that after data comparison and processing are completed, the test results will be output according to a predetermined format. The output content will include at least the test values ​​of each blood chemical indicator, the corresponding allowable fluctuation threshold, the degree of exceedance, and the compatibility index, and will be stored in tabular or structured data form. The output results can be grouped and arranged according to the concentration of degradation product solutions, so that the differences between blood chemical test results under different concentration conditions can be presented intuitively.

[0055] Simultaneously, following the same recording, processing, and output procedures as described above, the test results of the prepared blank control reaction system samples were processed. The blank control test results and the test results of the reaction system samples containing degradation products were stored in the same data structure. All test results retained the original data source information after output, including the test batch, test time, and sample number.

[0056] Furthermore, after recording, comparing, and outputting the blood chemistry test results, the data obtained from different test batches are correlated, organized, and stored in batches. This correlation and organization uses the prepared degradation product solution of the implantable medical device as the index object, and aggregates the blood reaction system sample data corresponding to each degradation product solution, so that the test results under the same degradation product conditions form an independent dataset.

[0057] During the correlation and collation process, each dataset must contain at least the following: concentration information of degradation product solutions, identification of reaction system construction conditions, detection values ​​of various blood chemical indicators, detection values ​​of blank control, allowable fluctuation thresholds, relative offset, degree of exceedance, and calculated and output compatibility index. The above data are arranged in a unified field order within the same dataset, without merging or simplifying the original values.

[0058] For test results obtained at different times or from different batches, batch identification is used for differentiation. Each batch is assigned a unique batch number in the data record, along with the corresponding test date, test time period, and sample number range. This allows data obtained under the same degradation product conditions from different batches to be differentiated and traced using the batch number.

[0059] It should be noted that after data association and batch identification are completed, the processed data is stored in a structured format. This structured storage is implemented using either tabular or database methods, with each field name consistent with the output data name. For multiple batches of test data under the same degradation product conditions, each batch of data remains independent within the storage structure, and no cross-batch merging is performed.

[0060] During data storage, complete detection data of the blank control reaction system samples are also retained. The blank control data and the corresponding batch of degradation product reaction system data are stored using the same data structure and linked by batch number to ensure rapid identification of the correspondence when a comparison is needed. All stored data retains its original detection source identifier, and the data content is not manually revised.

[0061] After completing the batch storage process described above, the stored data undergoes integrity verification. This verification includes checking field completeness, consistency, and for any missing data. The verification process is solely for confirming the integrity of the data records and does not adjust the test values ​​themselves. The verified data is then saved as the final data record for this blood chemistry testing procedure.

[0062] Example 2, one embodiment of the present invention, provides a blood testing method for compatibility with degradation products of implantable medical devices. In order to verify the beneficial effects of the present invention, scientific demonstration is carried out through economic benefit calculation and simulation experiments.

[0063] First, a biodegradable polymer implant material (using samples from the same batch of raw materials and manufactured using the same process to represent actual device materials) was selected as the degradation treatment target. After sequential washing with deionized water and organic solvents, the samples were dried under controlled temperature conditions and then placed in a buffer solution with an ionic composition matching the body fluid environment and a pH within the physiological range. The samples were then immersed in the solution under sealed conditions at temperatures close to the in vivo environment to obtain an immersion solution containing degradation products. After immersion, the immersion solution was first centrifuged to remove insoluble residues, then filtered through micropores to obtain a clear degradation product solution. This solution was then serially diluted with isotonic buffer of the same composition to create four concentration conditions: 1×, 1 / 2×, 1 / 4×, and 1 / 8×. Simultaneously, a buffer solution without the material was prepared as a blank control.

[0064] Blood samples were collected under aseptic conditions and anticoagulated. The plasma matrix was then separated by centrifugation and equilibrated with an isotonic buffer solution identical to the degradation system to form pretreated blood samples. These pretreated blood samples were mixed with degradation product solutions of varying concentrations at predetermined ratios and reacted within a controlled temperature and time. After the reaction, the temperature was lowered to terminate the reaction, and the supernatant was obtained by centrifugation again as the test sample. A blank control reaction system was prepared from pretreated blood samples and a buffer solution without the material using the same procedure. Blood chemistry tests simultaneously measured hemolysis-related, complement-related, coagulation-related, and inflammation-related chemical indicators. The permissible fluctuation threshold was obtained from repeated testing of the blank control reaction system samples and was consistently applied within the same batch of tests. Finally, the test values, threshold parameters, and compatibility indices under different concentration conditions were uniformly recorded, compiled, and structured for output. The data was stored and verified by batch number to ensure traceability. For comparison, two control groups were set up: Existing Technology A (detecting only hemolysis rate) and Existing Technology B (detecting multiple indicators but not introducing blank statistical thresholds or outputting a comprehensive index).

[0065] Table 1. Blood compatibility test data of degradation products from implanted medical devices.

[0066] As shown in Table 1, in terms of the completeness of evaluation dimensions, existing technology A only evaluates based on the hemolysis rate. Under the condition of 1× degradation products, the hemolysis rate is 0.68%, which is still near the common hemolysis safety threshold and is difficult to reflect the potential impact of degradation products on the blood system. However, the data from the examples show that under the same conditions, the complement activation index C3a increased to 225 ng / mL, the coagulation-related index TAT increased to 17.5 ng / mL, and the inflammatory factor IL-6 increased to 17.0 pg / mL, indicating that the blood system has undergone a significant multi-pathway chemical response. This invention, by simultaneously collecting multiple blood chemical indicators, can identify changes in complement, coagulation, and inflammatory pathways even when the hemolysis reaction is not significant, avoiding the information loss caused by evaluation with a single indicator.

[0067] Regarding stability assessment, while existing technology B detects multiple blood chemical indicators, it only describes the absolute changes in the detected values ​​and does not introduce a blank control to form a natural fluctuation baseline, making it difficult to distinguish between detection noise, individual differences, and actual material effects. In contrast, this invention uses the statistical results of the blank control reaction system to determine the allowable fluctuation threshold, only including changes exceeding the natural fluctuation range in the effective perturbation contribution. In the example, the number of exceeding indicators was 4 under the 1× condition, while it decreased to 0 under the 1 / 8× condition, demonstrating that this invention can clearly distinguish between the natural fluctuation range and abnormal changes caused by materials, significantly improving the stability and reliability of the detection results.

[0068] Regarding dose-response comparability, the data from the examples show that as the concentration of degradation products gradually decreases from 1× to 1 / 8×, indicators such as C3a, TAT, and IL-6 exhibit a consistent decreasing trend, and the compatibility index gradually decreases from 1.61 to 0.00, demonstrating a good concentration-dependent relationship. These results indicate that the present invention can not only identify the presence of blood chemical disturbances but also perform stratified quantification of different concentration conditions within the same evaluation framework, continuously characterizing the relationship between the degree of material degradation and the intensity of blood response—something difficult to achieve with existing technologies.

[0069] Furthermore, in terms of result presentation and data management, this invention aggregates and outputs multi-indicator information through a compatibility index, enabling complex multi-dimensional detection results to be characterized by a single quantitative parameter, while retaining the information of each individual indicator and its threshold, facilitating horizontal comparison between different batches and different material conditions. In the embodiments, the same material under different concentration conditions forms a structured dataset, supporting batch identification and traceability, which is significantly superior to existing solutions that only provide discrete detection values.

[0070] In summary, as can be clearly seen from Table 1, this invention, without relying on a single hemolysis criterion, introduces a blank control statistical baseline and a multi-index aggregation quantification mechanism, which can more comprehensively, stably and comparablely reflect the impact of implanted medical device degradation products on the blood chemical system. It overcomes the shortcomings of existing technologies in terms of single evaluation dimensions, unstable judgment, and difficulty in structured comparison of results, demonstrating significant technical advantages and practical value.

[0071] Example 3, one embodiment of the present invention, provides a blood detection system for compatibility with degradation products of implantable medical devices, including a sample preparation module, a reaction construction module, and a detection quantification module.

[0072] The sample preparation module is used to prepare the test object, including controlled degradation of materials consistent with the actual implanted medical device to obtain degradation product solution, and collection, anticoagulation, separation and environmental adjustment of blood samples to form a basic sample; the reaction construction module is used to mix the pretreated blood sample with degradation product solution of different concentrations under controlled conditions and complete the reaction process to obtain the reaction system sample; the detection and quantification module is used to detect the blood chemical indicators in the reaction system sample, and quantify the detection results based on blank control statistics to output the detection results characterizing the blood compatibility of degradation products.

[0073] If a function is implemented as a software functional unit and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of this invention, or the part that contributes to the prior art, or a part of the technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute all or part of the steps of the methods of the various embodiments of this invention. The aforementioned storage medium includes various media capable of storing program code, such as USB flash drives, portable hard drives, read-only memory (ROM), random access memory (RAM), magnetic disks, or optical disks.

[0074] The logic and / or steps represented in the flowchart or otherwise described herein, for example, can be considered as a sequenced list of executable instructions for implementing logical functions, and can be embodied in any computer-readable medium for use by, or in conjunction with, an instruction execution system, apparatus, or device (such as a computer-based system, a processor-including system, or other system that can fetch and execute instructions from, an instruction execution system, apparatus, or device). For the purposes of this specification, "computer-readable medium" can be any means that can contain, store, communicate, propagate, or transmit programs for use by, or in conjunction with, an instruction execution system, apparatus, or device.

[0075] More specific examples (a non-exhaustive list) of computer-readable media include: electrical connections (electronic devices) having one or more wires, portable computer disk drives (magnetic devices), random access memory (RAM), read-only memory (ROM), erasable and editable read-only memory (EPROM or flash memory), fiber optic devices, and portable optical disc read-only memory (CDROM). Furthermore, computer-readable media can even be paper or other suitable media on which programs can be printed, because programs can be obtained electronically, for example, by optically scanning the paper or other medium, followed by editing, interpreting, or otherwise processing as necessary, and then stored in computer memory.

[0076] It should be understood that various parts of the present invention can be implemented using hardware, software, firmware, or a combination thereof. In the above embodiments, multiple steps or methods can be implemented using software or firmware stored in memory and executed by a suitable instruction execution system. For example, if implemented in hardware, as in another embodiment, it can be implemented using any one or a combination of the following techniques known in the art: discrete logic circuits having logic gates for implementing logical functions on data signals, application-specific integrated circuits (ASICs) having suitable combinational logic gates, programmable gate arrays (PGAs), field-programmable gate arrays (FPGAs), etc. It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

[0077] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A blood testing method for the biocompatibility of degradation products from implantable medical devices, characterized in that, include: By cleaning and drying materials identical to those of actual implanted medical devices, and then subjecting them to controlled degradation in a buffer solution under physiological conditions, a solution of implanted medical device degradation products after solid-liquid separation and gradient dilution is obtained. Blood samples are then aseptically collected, anticoagulated, centrifuged, and adjusted to an isotonic environment to prepare pretreated blood samples. Pretreated blood samples were mixed with degradation product solutions of different concentrations in a set ratio and the reaction was completed under controlled temperature and time conditions. Then, the supernatant of the reaction system was obtained for detection through termination and separation operations. Blood chemical parameters in the supernatant of the reaction system were detected, and the allowable fluctuation threshold was determined based on the blank control statistics. The relative deviation, degree of exceedance, and compatibility index of the polymer output of each parameter were calculated. The blood chemical test values, threshold parameters and compatibility indices obtained under different degradation product concentration conditions are uniformly recorded, compared and organized and structured for output, resulting in a test result dataset.

2. The blood testing method for compatibility of degradation products of implantable medical devices as described in claim 1, characterized in that: The controlled degradation under physiological conditions by placing the material in a buffer solution includes selecting materials that are consistent with the actual implanted medical device in terms of material composition and preparation process as the treatment object, cleaning and drying the material, and then immersing it in a buffer solution with ionic composition matching the body fluid environment and pH within the physiological range, so that the material undergoes natural degradation under the conditions of the body environment. No additional chemical catalysts or external reaction-promoting conditions are introduced during the degradation process; After the degradation treatment is completed, the buffer solution is subjected to solid-liquid separation to retain only the degradation product components in the dissolved state, and the obtained degradation product solution is subjected to multi-stage concentration treatment.

3. The blood testing method for compatibility of degradation products of implantable medical devices as described in claim 2, characterized in that: The preparation of pretreated blood samples includes collecting blood samples under aseptic conditions and performing anticoagulation treatment. Centrifuge the anticoagulated blood sample to obtain plasma or serum components; An isotonic solution with the same composition as the buffer solution used for the degradation product solution was used to adjust the environment of the blood samples so that different blood samples could be kept consistent in terms of ion composition and osmotic pressure. The environmentally conditioned blood samples were equilibrated under controlled temperature conditions.

4. The blood testing method for compatibility with degradation products of implantable medical devices as described in claim 3, characterized in that: The subsequent termination and separation operation to obtain the supernatant of the reaction system for detection includes mixing the pretreated blood sample with degradation product solutions of different concentration gradients in a predetermined ratio, so that the blood sample maintains a volume fraction in the reaction system. The mixed reaction system was subjected to reaction treatment under controlled temperature and time conditions. The system was kept closed during the reaction process, and no sampling or liquid replenishment was performed. After the reaction is complete, the reaction is terminated by lowering the system temperature, and the reaction system is then separated.

5. The blood testing method for compatibility of degradation products of implantable medical devices as described in claim 4, characterized in that: The detection of blood chemical indicators in the supernatant of the reaction system includes comparing the detection results of the reaction system sample containing degradation products with the detection results of the blank control reaction system sample to obtain the degree of change of each blood chemical indicator relative to the blank control. Using the natural fluctuation range of the blank control reaction system samples under repeated testing conditions as a reference baseline, the evaluation of changes in blood chemical indicators is based on control statistics.

6. The blood testing method for compatibility of degradation products of implantable medical devices as described in claim 5, characterized in that: The method of determining the allowable fluctuation threshold based on blank control statistics, calculating the relative offset, degree of exceeding the standard, and compatibility index of aggregated output for each indicator includes recording the excess portion as an effective perturbation contribution of the indicator when evaluating the changes of each blood chemical indicator relative to the blank control exceeds the natural fluctuation range of the indicator under blank conditions. When the degree of change does not exceed the natural fluctuation range, the indicator is not included in the calculation of the overall blood chemical disturbance level.

7. The blood testing method for compatibility with degradation products of implantable medical devices as described in claim 6, characterized in that: The allowable fluctuation threshold is determined based on blank control statistics, and the relative offset, degree of exceeding the standard, and compatibility index of each indicator are calculated. This includes summarizing the perturbation contributions of each indicator when performing aggregation processing on the effective perturbation contributions of blood chemical indicators. Through polymerization, a compatibility index is output to characterize the overall degree of perturbation of blood chemistry under different concentrations of degradation products.

8. A system employing a blood testing method for compatibility with degradation products of implantable medical devices as described in any one of claims 1 to 7, characterized in that: It includes a sample preparation module, a reaction construction module, and a detection and quantification module; The sample preparation module is used to prepare the test object, including controlled degradation of materials consistent with the actual implanted medical device to obtain degradation product solution, and collection, anticoagulation, separation and environmental adjustment of blood samples to form basic samples; The reaction construction module is used to mix pretreated blood samples with degradation product solutions of different concentrations under controlled conditions and complete the reaction process to obtain a reaction system sample; The detection and quantification module is used to detect blood chemical indicators in the reaction system sample, and to quantify the detection results based on blank control statistics, outputting detection results characterizing the blood compatibility of degradation products.

9. A computer device comprising a memory and a processor, wherein the memory stores a computer program, characterized in that, When the processor executes the computer program, it implements the steps of the blood testing method for compatibility of degradation products of implantable medical devices as described in any one of claims 1 to 7.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the computer program is executed by the processor, it implements the steps of the blood testing method for compatibility of degradation products of implantable medical devices as described in any one of claims 1 to 7.

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