报告编号：YN-CXQ-CR01
Report ID: YN-CXQ-CR01

版本号和日期：V2.0, 20250403
Version number and date: V2.0, 20250403

一次性使用凝胶补片成型器临床使用的安全性和有效性的前瞻性、多中心、随机、平行对照、优效性临床试验报告
Prospective, multicenter, randomized, parallel-controlled, superiority clinical trial report on the safety and efficacy of single-use gel patch formers for clinical use

试验医疗器械名称：一次性使用凝胶补片成型器
Name of the test medical device: Disposable gel patch former

临床试验使用的型号规格：YN-PAT 35
Model specification used in clinical trials: YN-PAT 35

需进行临床试验审批的第三类医疗器械 ：是 否
Class III medical devices subject to clinical trial approval: Yes No 

临床试验组长单位：浙江大学医学院附属邵逸夫医院
Clinical trial team leader unit: Run Shaw Hospital Affiliated to Zhejiang University School of Medicine

协调研究者：王强
Coordinating Investigator: Wang Qiang

临床试验开始时间：2024年10月10日
Clinical trial start time: October 10, 2024

临床试验结束时间（最后一例受试者出组）：2025年1月12日
End time of clinical trial (last subject out of the group): January 12, 2025

方案编号：YNCXQ-20240820
Scheme number: YNCXQ-20240820

方案版本号和日期：V4.0, 2025年3月17日
Solution version number and date: V4.0, March 17, 2025

申办者：杭州源囊生物科技有限公司
Sponsor: Hangzhou Yuannang Biotechnology Co., Ltd

原始资料保存地点：
Where the original materials are stored:

浙江大学医学院附属邵逸夫医院
Run Shaw Hospital Affiliated to Zhejiang University School of Medicine

宁波市第六医院
Ningbo Sixth Hospital

填写说明
Fill in the instructions

1.申办者、主要研究者应当本着认真负责的态度，严格按照临床试验方案实施临床试验，公正、客观地完成临床试验报告。
1. The sponsor and principal investigator shall conduct clinical trials in strict accordance with the clinical trial plan in a serious and responsible manner, and complete the clinical trial report fairly and objectively.

2.申办者、主要研究者应当对试验报告的真实性和科学性负责。
2. The sponsor and principal investigator shall be responsible for the authenticity and scientific nature of the test report.

3.本报告应当由主要研究者签名和注明日期，经医疗器械临床试验机构审核签章后交申办者。多中心临床试验报告应当由协调研究者签名、注明日期，经组长单位医疗器械临床试验机构审核签章后交申办者。
3. This report shall be signed and dated by the principal investigator, and submitted to the sponsor after being reviewed and signed by the medical device clinical trial institution. The multicenter clinical trial report shall be signed and dated by the coordinating investigator, and submitted to the sponsor after being reviewed and signed by the medical device clinical trial institution of the team leader unit.

4.报告应当有目录。
4. The report should have a table of contents.

5.可根据报告需要增加缩略语表、参考文献等内容。
5. Abbreviations, references, etc. can be added according to the needs of the report.

目 录
Table of contents

1. 报告摘要 1
1. Report Summary 1

2. 临床试验的背景 4
2. Background of clinical trials 4

3. 临床试验目的 5
3. Purpose of clinical trial 5

4. 临床试验的实施 6
4. Implementation of clinical trials6

4.1. 试验流程图 6
4.1. Test flow diagram 6

4.2. 受试者选择 9
4.2. Subject Selection 9

4.3. 临床试验样本量 10
4.3. Clinical trial sample size 10

4.4. 试验医疗器械 10
4.4. Test medical devices 10

4.5. 临床评价标准 11
4.5. Clinical evaluation criteria 11

5. 统计分析方法 16
5. Statistical analysis methods 16

5.1. 分析数据集 16
5.1. Analyze datasets 16

5.2. 受试者剔除标准 16
5.2. Subject Exclusion Criteria 16

5.3. 统计分析方法 17
5.3. Statistical analysis methods 17

5.4. 缺失值和异常值的处理 17
5.4. Handling of missing and outlier values 17

6. 临床试验结果 19
6. Clinical trial results 19

6.1. 分析数据集 19
6.1. Analyze the dataset 19

6.2. 人口学资料和基线特征分析 20
6.2. Demographic data and baseline characteristic analysis 20

6.3. 有效性评价指标 23
6.3. Effectiveness evaluation index 23

6.4. 安全性评价 26
6.4. Safety evaluation 26

6.5. 不良事件及其处理情况 30
6.5. Adverse events and their treatment 30

6.6. 器械缺陷 31
6.6. Defects in instruments 31

7. 临床试验结果分析、讨论及其适应症、禁忌症和注意事项等 32
7. Analysis and discussion of clinical trial results and their indications, contraindications and precautions, etc.32

7.1. 临床试验结果分析、讨论 32
7.1. Analysis and discussion of clinical trial results 32

7.2. 适应症 34
7.2. Indications 34

7.3. 禁忌症 34
7.3. Contraindications 34

7.4. 注意事项 35
7.4. Precautions 35

8. 临床试验结论 35
8. Clinical trial conclusions 35

9. 存在问题及改进建议 35
9. Existing problems and suggestions for improvement 35

10. 多中心临床试验所有临床试验机构 36
10. Multicenter clinical trials All clinical trial institutions 36

11. 试验人员名单 36
11. List of test personnel 36

12. 伦理情况说明 37
12. Explanation of ethical situations 37

13. 其他需要说明的情况 38
13. Other circumstances that need to be explained 38

13.1. 方案修订情况说明 38
13.1. Description of the revision of the plan 38

13.2. 试验方案的偏离情况 39
13.2. Deviation of the test protocol 39

14. 协调研究者签名，注明日期，临床试验机构审核签章 40
14. Coordinate the signature of the researcher, indicate the date, and the review signature of the clinical trial institution 40

报告摘要
Report Summary

本次临床试验共筛选41例受试者，筛选失败1例，筛选期退出2例，最后成功入组38例，纳入全分析集（FAS）38例，其中试验组19例，对照组19例；符合方案集（PPS）38例，其中试验组19例，对照组19例；纳入安全分析集（SS）37例，其中试验组18例，对照组19例，均符合统计学要求的试验组和对照组各至少18例，总病例数36例。此外，次要评价指标中，生长因子浓度、极限拉力强度和血小板浓度三个指标在符合方案集的前提下，将所有受试者的血液分成2组（补片组和PRP组）进行配对试验，因此每组样本量为38例。
A total of 41 subjects were screened in this clinical trial, 1 case failed screening, 2 cases withdrew from the screening period, and finally 38 cases were successfully enrolled and included in the full analysis set ( FAS), including 19 in the experimental group and 19 in the control group. 38 cases met the protocol set (PPS), including 19 cases in the experimental group and 19 cases in the control group. Thirty-seven cases were included in the safety analysis set (SS), including 18 cases in the experimental group and 19 cases in the control group, all of which met the statistical requirements of at least 18 cases in the experimental group and the control group. The total number of cases was 36. In addition, the blood of all subjects was divided into two groups (patch group and PRP group) for pairing experiments under the premise that the three indicators of growth factor concentration, ultimate tensile intensity and platelet concentration were in accordance with the protocol set, so the sample size of each group was 38 Example.

人口学资料
Demographic data

人口统计学指标包括年龄、性别、身高、体重，采用全分析集（FAS）进行分析，结果如下：
Demographic indicators include age, gender, height, and weight, and are analyzed using the full analysis set (FAS), and the results are as follows:

年龄，试验组平均年龄为（57.95±12.08）岁，对照组平均年龄为（61.63±7.05）岁，组间比较差异不具有统计学意义（P>0.05）。
The average age of the experimental group was (57.95±12.08) years old and that of the control group was (61.63±7.05) years, and the difference between the groups was not statistically significant (P>0.05).

性别，试验组男性18例，占比94.74%，女性1例，占比5.26%；对照组男性13例，占比68.42%，女性6例，占比31.58%，组间比较差异具有统计学意义（P＜0.05）。
Gender, 18 males in the experimental group, accounting for 94.74%, and 1 female, accounting for 5.26%. In the control group, there were 13 males, accounting for 68.42% and 6 females, accounting for 31.58%, and the differences between groups were statistically significant (P<0.05）。

身高，试验组平均身高为（169.38±7.23）cm，对照组平均身高为（168.01±8.38）cm，组间比较差异不具有统计学意义（P>0.05）。
The average height of the experimental group was (169.38±7.23) cm, and the average height of the control group was (168.01±8.38) cm, and the difference between the groups was not statistically significant (P>0.05). ）。

体重，平均体重为（68.41±11.99）kg，对照组平均体重为（64.42±9.96）kg，组间比较差异不具有统计学意义（P>0.05）。
The mean weight was (68.41±11.99) kg, and the mean weight of the control group was (64.42±9.96) kg, and the difference between the groups was not statistically significant (P>0.05）。

既往史情况
Past history

既往史情况包括既往病史和用药史，采用全分析集（FAS）进行分析，结果如下：
The anamnesis includes past medical history and medication history, which were analyzed using the full analysis set (FAS), and the results are as follows:

既往病史，试验组中有既往病史的受试者19例，占比100%，无既往病史的受试者0例，占比0%；对照组中有既往病史的受试者19例，占比100.00%，无既往病史的受试者0例，占比0%，组间比较差异不具有统计学意义（P>0.05）。
In the experimental group, there were 19 subjects with past medical history, accounting for 100%, and 0 subjects with no past medical history, accounting for 0%. In the control group, there were 19 subjects with a history of medical history, accounting for 100.00%, and 0 subjects with no past medical history, accounting for 0%. There was no significant difference between groups (P>0.05).

用药史，试验组中有用药史的受试者19例，占比100%，无用药史的受试者0例，占比0%；对照组中有用药史的受试者19例，占比100.00%，无用药史的受试者0例，占比0%，组间比较差异不具有统计学意义（P>0.05）。
Medication history, 19 subjects in the experimental group had a history of medication, accounting for 100%, and 0 subjects had no history of medication, accounting for 0%. In the control group, there were 19 subjects with a history of medication, accounting for 100.00%, and 0 subjects with no history of medication, accounting for 0%, There was no significant difference between groups (P>0.05).

过敏史，试验组中有过敏史的受试者2例，占比10.53%，无用药史的受试者17例，占比89.47%；对照组中有用药史的受试者1例，占比5.26%，无用药史的受试者18例，占比94.74%，组间比较差异不具有统计学意义（P>0.05）。
Allergy history, 2 subjects in the experimental group had a history of allergy, accounting for 10.53%, and 17 subjects had no history of medication, accounting for 89.47%. In the control group, there was 1 subject with a history of medication, accounting for 5.26%, and 18 subjects with no history of medication, accounting for 94.74%. There was no significant difference between groups (P>0.05).

创面大小情况
Wound size

基于FAS的分析结果显示，试验组中创面大小为小、浅表的受试者11例，占比61.11%，有暴露的关节或骨头的受试者6例，占比33.33%，广泛、深且累及周边组织的受试者1例，占比5.56%；对照组中创面大小为小、浅表的受试者10例，占比55.56%，有暴露的关节或骨头的受试者2例，占比11.11%，广泛、深且累及周边组织的受试者6例，占比33.33%；组间比较差异不具有统计学意义（P>0.05）。
The results of FAS-based analysis showed that there were 11 subjects in the experimental group with small and superficial wound size, accounting for 61.11%, and exposed joints or bones6 cases, accounting for 33.33%, and 1 case with extensive, deep and involving surrounding tissues, accounting for 5.56%. In the control group, 10 subjects with small and superficial wound size, accounting for 55.56%, and 2 subjects with exposed joints or bonescases, accounting for 11.11%, and 6 subjects with extensive, deep and involving surrounding tissues, accounting for 33.33%; There was no significant difference between groups (P>0.05).

清创评估得分
Debridement assessment score

基于FAS的分析结果显示，试验组清创评估得分为12.58±0.96分；对照组清创评估得分为12.58±0.96分；组间比较差异不具有统计学意义（P>0.05）
The results of FAS-based analysis showed that the debridement assessment score of the experimental group was 1 2.58±0.96 points. The debridement assessment score of the control group was 12.58±0.96 points. There was no significant difference between groups (P>0.05).

研究器械使用情况
Study device use

在全分析集（FAS）中，试验组均使用一次性使用凝胶补片成型器制备的凝胶补片，型号：YN-PAT 35，共19例(占比100.00%)；对照组使用二次离心法制备的富血小板血浆凝胶，共19例(占比100.00%)。
In the full analysis set (FAS), the experimental group used a single-use gel patch former, model: YN-PAT 35, a total of 19 cases (accounting for 100.00%). A total of 19 cases (100.00%) of platelet-rich plasma gels were prepared by secondary centrifugation in the control group.

有效性评价指标
Effectiveness evaluation indicators

主要评价指标为血小板浓度合格率。
The main evaluation index was the qualified rate of platelet concentration.

在全分析集（FAS）中，试验组共有12例血小板浓度符合设定阈值，7例不符合，血小板浓度合格率63.16%；对照组共有2例血小板浓度符合设定阈值，17例不符合，血小板浓度合格率10.53%；组间比较差异具有统计学意义（P＜0.05）。两组血小板浓度合格率差值为52.63%(95%CI：22.02%～73.22%)，其95%CI置信区间下限为22.02%，大于优效界值10%，可推断试验组的有效性优于对照组。
In the full analysis set (FAS), a total of 12 platelet concentrations in the experimental group met the set threshold, and 7 cases did not, and the platelet concentration was qualified 63.16%； In the control group, 2 platelet concentrations met the set threshold, 17 cases did not, and the platelet concentration pass rate was 10.53%. The difference between the groups was statistically significant (P<0.05). The difference in the qualified rate of platelet concentration between the two groups was 52.63% (95%CI: 22.02%~73.22%) The lower limit of the 95% CI confidence interval was 22.02%, which was 10% higher than the superiority cut-off, inferring that the effectiveness of the experimental group was better than that of the control group.

在符合方案集（PPS）中，试验组共有12例血小板浓度符合设定阈值，7例不符合，血小板浓度合格率63.16%；对照组共有2例血小板浓度符合设定阈值，17例不符合，血小板浓度合格率10.53%；组间比较差异具有统计学意义（P＜0.05）。两组血小板浓度合格率差值为52.63%(95%CI：22.02%～73.22%)，其95%CI置信区间下限为22.02%，大于优效界值10%，可推断试验组的有效性优于对照组。符合方案集（PPS）的结论与全分析集（FAS）一致。
In the protocol set (PPS), a total of 12 platelet concentrations in the experimental group met the set threshold, and 7 did not, the platelet concentration pass rate was 63.16%; In the control group, 2 platelet concentrations met the set threshold, 17 cases did not, and the platelet concentration pass rate was 10.53%. The difference between the groups was statistically significant (P<0.05). The difference in the qualified rate of platelet concentration between the two groups was 52.63% (95%CI: 22.02%~73.22%) The lower limit of the 95% CI confidence interval was 22.02%, which was 10% higher than the superiority cut-off, inferring that the effectiveness of the experimental group was better than that of the control group. The conclusions of conformity with the protocol set (PPS) were consistent with the full analysis set (FAS).

综上，可证实试验组有效性优效于对照组的结论。
In summary, it can be confirmed that the effectiveness of the experimental group is better than that of the control group.

次要评价指标为术后术后三天创面细菌情况，生长因子浓度、极限拉力强度、术后伤口情况、产品使用性能、血小板浓度，具体统计分析结果如下：
The secondary evaluation indicators were the bacterial condition of the wound, the concentration of growth factors, the ultimate tensile strength, the postoperative wound, the performance of the product, and the platelet concentration in the three days after the operation, and the specific statistical analysis results were as follows:

术后三天创面细菌情况：在全分析集（FAS）中，试验组术后三天创面细菌情况评分为（0.833±0.514），对照组术后三天创面细菌情况评分为（0.667±0.594），组间比较差异不具有统计学意义（P>0.05）。在符合方案集（PPS）中，试验组术后三天创面细菌情况评分为（0.833±0.514），对照组术后三天创面细菌情况评分为（0.667±0.594），组间比较差异不具有统计学意义（P>0.05。
Wound bacteria at three days after surgery: In the full analysis set (FAS), the bacterial status score of the wound in the experimental group was (0.833±0.514, and the score of wound bacteria in the control group was (0.667±0.594 at three days after surgery), and the difference between the groups was not statistically significant (P% 3E0.05）。 In the conformity set (PPS), the bacterial score of the wound in the experimental group was (0.833±0.514 at three days after surgery, and the score of bacterial status in the wound at three days after operation in the control group was (0.667±0.594), and the difference between the groups was not statistically significant ( P>0.05。

生长因子浓度：在基于符合方案集（PPS）的基础上，补片组浸提液中生长因子PDGF-BB的浓度为（5.89±4.35）pg/mL，PRP组浸提液中生长因子PDGF-BB的浓度为（7.13±5.16）pg/mL，组间比较差异不具有统计学意义（P>0.05）。补片组浸提液中生长因子TGF-β1的浓度为（2.52±2.42）ng/mL，PRP组浸提液中生长因子TGF-β1的浓度为（2.49±2.50）ng/mL，组间比较差异不具有统计学意义（P>0.05）。补片组浸提液中生长因子IL-1β的浓度为（2.62±6.88）pg/mL，PRP组浸提液中生长因子IL-1β的浓度为（3.26±7.85）pg/mL，组间比较差异不具有统计学意义（P>0.05）。
Growth factor concentration: Based on the conformity to protocol set (PPS), the concentration of growth factor PDGF-BB in the patch group extract was (5.89±4.35) pg/mL, PRP The concentration of growth factor PDGF-BB in the extract was (7.13±5.16) pg/mL, and the difference between the groups was not statistically significant (P>0.05). ）。 The concentration of growth factor TGF-β1 in the patch group was (2.52±2.42) ng/mL, and the growth factor TGF-β1 in the PRP group was in the extractThe concentration was (2.49±2.50) ng/mL, and the difference between groups was not statistically significant (P>0.05). The concentration of growth factor IL-1β in the patch group was (2.62±6.88) pg/mL, and the growth factor IL-1β in the PRP group was (2.626.88) pg/mL The concentration was (3.26±7.85) pg/mL, and the difference between the groups was not statistically significant (P>0.05).

极限拉力强度：在基于符合方案集（PPS）的基础上，补片组极限拉力强度为（0.711±0.141），PRP组极限拉力强度为（0.393±0.106）N，补片组极限拉力强度显著高于PRP组（P＜0.05）。
Ultimate tensile strength: Based on the conformity scheme set (PPS), the ultimate tensile strength of the patch group was (0.711±0.141, and the ultimate tensile strength of the PRP group was (0.393±0.106) N, the ultimate tensile strength of the patch group was significantly higher than that of the PRP group (P<0.05).

术后伤口情况：在全分析集（FAS）中，试验组术后3天伤口情况得分为（0.21±0.42）分，对照组术后3天伤口情况得分为（0.28±0.46）分，组间比较差异不具有统计学意义（P>0.05）。在符合方案集（PPS）中，试验组术后3天伤口情况得分为（0.21±0.42）分，对照组术后3天伤口情况得分为（0.28±0.46）分，组间比较差异不具有统计学意义（P>0.05）。
Postoperative wound status: In the full analysis set (FAS), the wound condition score of the experimental group at 3 days after operation was (0.21±0.42) points, and the control group was controlled The wound status score at 3 days after surgery was (0.28±0.46), and the difference between the groups was not statistically significant (P>0.05). ）。 In the protocol set (PPS), the wound condition score was (0.21±0.42) in the experimental group and (0.210.42) after surgery The score of the wound situation at 3 days was (0.28±0.46), and the difference between groups was not statistically significant (P>0.05).

产品使用性能：在全分析集（FAS）中，试验组中产品使用性能评价为满意的共19例，不满意的0例，产品使用性能满意度为100.00%。在符合方案集（PPS）中，试验组中产品使用性能评价为满意的共19例，不满意的0例，产品使用性能满意度为100.00%。
Product use performance: In the full analysis set (FAS), a total of 19 cases in the experimental group were satisfied with the product use performance evaluation and 0 cases were dissatisfied, and the product use performance satisfaction rate was 100.00%. In the PPS protocol set, 19 cases in the experimental group were satisfied with the performance of the product, 0 cases were dissatisfied, and the satisfaction rate of the product performance was 100.00%。

血小板浓度：在基于符合方案集（PPS）的基础上，补片组血小板浓度为（458±285）×10⁹/L，PRP组血小板浓度为（253±181）×10⁹/L，补片组的血小板浓度显著高于PRP组（P＜0.05）。
Platelet concentration: Based on the conformity to protocol set (PPS), the platelet concentration in the patch group was (458±285) ×10⁹/L, and the platelet concentration in the PRP group was ( 253±181)×10⁹/L, and the platelet concentration in the patch group was significantly higher than that in the PRP group (P<0.05）。

综合以上分析，经试验组与对照组相比，试验器械制备的血小板凝胶补片优于富血小板血浆凝胶，有效性满足临床需要。
Based on the above analysis, compared with the control group, the platelet gel patch prepared by the experimental device was better than the platelet-rich plasma gel, and the effectiveness met the clinical needs.

安全性评价指标
Safety evaluation indicators

实验室检查异常情况：在安全分析集（SS）中，试验组和对照组术后3天血常规异常发生率组间比较差异不具有统计学意义（P＞0.05）。试验组和对照组术后3天肝功能异常发生率组间比较差异不具有统计学意义（P＞0.05）。试验组和对照组术后3天肾功能异常发生率组间比较差异不具有统计学意义（P＞0.05）。试验组和对照组术后3天C反应蛋白异常发生率组间比较差异不具有统计学意义（P＞0.05）。
Laboratory abnormalities: In the safety analysis set (SS), there was no significant difference in the incidence of blood routine abnormalities in the experimental group and the control group at 3 days after surgery (P>0.05). There was no significant difference in the incidence of abnormal liver function at 3 days after operation between the experimental group and the control group (P>0.05). There was no significant difference between the incidence of abnormal renal function at 3 days after operation between the experimental group and the control group (P>0.05). There was no significant difference in the incidence of C-reactive protein abnormalities between the experimental group and the control group at 3 days after operation (P>0.05).

生命体征情况：在安全分析集（SS）中，分析术后3天生命体征情况，试验组和对照组的收缩压分别为117.74±11.9 mmHg和123.50±15.14 mmHg，组间比较差异不具有统计学意义（P>0.05）；试验组和对照组的舒张压分别为74.16±8.27 mmHg和73.50±9.58 mmHg，组间比较差异不具有统计学意义（P>0.05）；试验组和对照组的呼吸分别为18.21±1.47 次/min和18.00±1.08 次/min，组间比较差异不具有统计学意义（P>0.05）；试验组和对照组的脉搏分别为73.26±8.10 次/min和73.22±6.91 次/min，组间比较差异不具有统计学意义（P>0.05）；试验组和对照组的体温分别为36.59±0.24 ℃和36.58±0.27 ℃，组间比较差异不具有统计学意义（P>0.05）。
Vital signs: In the safety analysis set (SS), the systolic blood pressure of the experimental group and the control group was 117.74±11.9 mmHg, respectively123.50±15.14 mmHg, and the difference between groups was not statistically significant (P>0.05). The diastolic blood pressure of the experimental group and the control group were 74.16±8.27 mmHg and 73.50±9.58 mmHg, respectively, and the difference between the groups was not statistically significant (P>0.05). ）； The respirations of the experimental group and the control group were 18.21±1.47 breaths/min and 18.00±1.08 breaths/min, respectively, and the comparison between the groups was not statistically significant (P>0.05）； The pulses of the experimental group and the control group were 73.26±8.10 beats/min and 73.22±6.91 beats/min, respectively, and the comparison between the groups was not statistically significant (P>0.05）； The body temperatures of the experimental group and the control group were 36.59±0.24 °C and 36.58±0.27 °C, respectively, and the difference between the groups was not statistically significant (P>0.05).。

不良事件和严重不良事件发生情况：在安全分析集（SS）中，试验组共有6例受试者发生不良事件，发生率为31.58%；对照组共8例受试者发生不良事件，发生率为44.44%，组间比较差异不具有统计学意义（P>0.05）。本临床试验中，未发生与器械相关的不良事件，未发生严重不良事件，未发生与器械相关的严重不良事件。
Occurrence of adverse events and serious adverse events: In the safety analysis set (SS), a total of 6 subjects in the experimental group had adverse events, with an incidence rate of 31.58%. A total of 8 subjects in the control group had adverse events, with an incidence rate of 44.44%, and the difference between groups was not statistically significant (P>0.05). In this clinical trial, there were no device-related adverse events, no serious adverse events, and no device-related serious adverse events.

综合以上分析，可证实杭州源囊生物科技有限公司委托浙江狄赛生物科技有限公司生产的一次性使用凝胶补片成型器在临床应用中是安全的，满足临床需要。
Based on the above analysis, it can be confirmed that the disposable gel patch molder entrusted by Hangzhou Yuansang Biotechnology Co., Ltd. to Zhejiang Disai Biotechnology Co., Ltd. is safe in clinical application and meets clinical needs.

临床试验的背景
Background of the clinical trial

数千年来，增强伤口组织愈合一直是医生的目标。随着中国加速进入老年化社会，创伤护理市场快速增长。很多患者，尤其是患有基础病的老年人受伤后，伤口未及时修复，容易发展成慢性创面，面临坏疽、截肢等风险。难愈性创面的治疗是一个持续存在的医疗问题，在中国，数千万患者饱受难愈性创面的折磨。以糖尿病足溃疡（Diabetic foot ulcer，DFU）为例，其治疗费用占糖尿病治疗总费用的25-50%。其中5%-8%的DFU的患者在第1年需要截肢，且截肢后5年约有45%-55%的患者死亡。难愈性创面已经成为一个患病群体基数大，急需解决的健康问题。
Enhancing wound tissue healing has been the goal of doctors for thousands of years. As China accelerates into an aging society, the trauma care market is growing rapidly. Many patients, especially the elderly with underlying diseases, are not repaired in time after injury, and are prone to develop into chronic wounds and face risks such as gangrene and amputation. Treatment of refractory wounds is an ongoing medical problem, with tens of millions of patients suffering from refractory wounds in China. Taking diabetic foot ulcer (DFU) as an example, its treatment cost accounts for 25-50% of the total cost of diabetes treatment. Among them, 5%-8% of DFU patients require amputation in the first year, and about 45%-55% of patients die 5 years after amputation. Refractory wounds have become a health problem with a large base of patients and urgently need to be solved.

目前难愈性创面的治疗方法主要包括坏死组织清创、感染控制、血运重建、局部减压和合并症治疗等。然而，这些治疗策略通常需要同时进行，并导致巨大的治疗成本和复杂性。为了改善难愈创面组织愈合，国际上一些公司开发了许多类型的新技术和促再生敷料产品，包括生长因子输送、基因治疗等。但由于难愈性创面的复杂性，不同的个体具有不同的生化特征，补充单一的生长因子或仅针对单一的基因难以达到理想的伤口愈合，且部分先进治疗方法存在未知风险。所以在国内这些治疗方法也未正式获得批准。自体PRP作为一种再生修复治疗方法，已在国内被广泛应用于骨折术后修复。国内外存在大量的临床研究证实自体PRP可以有效促进创面愈合。作为一种便捷无痛苦低风险的治疗手段，且富含大量生长因子，治疗效果显著，自体PRP治疗被广泛患者所接受。
At present, the treatment methods of refractory wounds mainly include necrotic tissue debridement, infection control, revascularization, local decompression and comorbidity treatment. However, these treatment strategies often need to be performed simultaneously and lead to significant treatment costs and complexities. In order to improve the healing of intractable wound tissue, some international companies have developed many types of new technologies and regenerative dressing products, including growth factor delivery, gene therapy, etc. However, due to the complexity of refractory wounds, different individuals have different biochemical characteristics, and it is difficult to achieve ideal wound healing by supplementing a single growth factor or targeting only a single gene, and some advanced treatments have unknown risks. Therefore, these treatments have not been officially approved in China. As a regenerative repair treatment, autologous PRP has been widely used in postoperative repair of fractures in China. There are a large number of clinical studies at home and abroad that confirm that autologous PRP can effectively promote wound healing. As a convenient, painless, low-risk treatment method, rich in a large number of growth factors, the therapeutic effect is remarkable, and autologous PRP treatment is widely accepted by patients.

尽管促创面愈合效果优异，但因为临床上组织创面的多样性，目前市面上没有很好的适应于创面修复的PRP产品，所以国内自体PRP/PRP凝胶在创面治疗中应用并不广泛。目前上市的PRP产品最终制成的多数为PRP液体，无法直接适用于难愈性创面等组织修复的治疗。有些产品结合了凝血酶，使PRP血浆中纤维蛋白原凝聚形成PRP凝胶。但是，自然成型的PRP凝胶结构松散，含水量极高。直接在伤口上使用会出现诸多不良后果：a) 自然成型的PRP凝胶具有极高的含水量，经纱布包扎后，凝胶中的水分会被纱布逐渐吸收，失水后的凝胶会立即内缩，会造成生长因子大量的流失，并造成纱布渗液，增加伤口进一步感染风险。b) 自然成型的PRP凝胶结构松散，易被降解。且凝胶表面湿润光滑，难以持续附着于伤口，极易因患者的移动而导致凝胶移位。c) 从微观结构中发现，自然成型的PRP凝胶的孔径大于白细胞和血小板（＞9μm），因此，无法有效地实现对白细胞和血小板的包载，易在体液的冲刷下快速流失并降解，无法起到持续促修复的作用。因此，PRP在难愈创面治疗使用时仍存在诸多不便和问题。所以急需一款能够改进PRP在难愈伤口应用的产品，以实现PRP在加速伤口组织愈合的良好治疗效果。
Although the wound healing effect is excellent, due to the diversity of clinical tissue wounds, there are no PRP products on the market that are well adapted to wound repair, so domestic autologous PRP/PRP gel is not widely used in wound treatment. Most of the PRP products currently on the market are finally made of PRP liquid, which cannot be directly applied to the treatment of tissue repair such as refractory wounds. Some products combine thrombin to make fibrinogen aggregate in PRP plasma to form PRP gels. However, naturally formed PRP gels have a loose structure and extremely high water content. There are many adverse consequences when used directly on the wound: a) Naturally formed PRP gel has a very high water content, after gauze bandaging, the water in the gel will be gradually absorbed by the gauze, and the gel will immediately shrink after water loss, which will cause a large loss of growth factors and cause gauze exudation, increasing the risk of further infection of the wound. b) Naturally formed PRP gels have a loose structure and are easily degraded. Moreover, the surface of the gel is moist and smooth, making it difficult to continue to adhere to the wound, and it is very easy to cause the gel to shift due to the patient's movement. c) From the microstructure, it is found that the pore size of the naturally formed PRP gel is larger than that of leukocytes and platelets (>9μm), so it cannot effectively realize the encapsulation of leukocytes and platelets, and is easy to be quickly lost and degraded under the washing of body fluids. It cannot play a role in promoting continuous repair. Therefore, there are still many inconveniences and problems in the treatment of refractory wounds. Therefore, there is an urgent need for a product that can improve the application of PRP in difficult-to-heal wounds to achieve a good therapeutic effect of PRP in accelerating wound tissue healing.

鉴于目前市面上多数PRP制备产品针对难愈创面使用的不便捷性，杭州源囊生物科技有限公司研究团队开发出一款可将PRP制备形成浓缩的PRP凝胶补片的成型器产品。该产品作为成型器，通过物理挤压的方式，不改变PRP凝胶的化学结构、生物性能，将松散的血浆凝胶制备成较高强度的血浆凝胶补片。该产品操作简单，制备时间短。挤压成型后的凝胶补片相比于自然成型PRP凝胶，凝胶补片具有更强的力学强度，可以用缝线进行与伤口组织的缝合，可以应伤口的形态随意裁剪；成型后的凝胶补片显著延长了凝胶的降解时间，提升生长因子缓释浓度和时长。目前，本产品已通过国家药品监督管理局（NMPA）认证的检验机构检验且结论为合格，为了进一步评价器械的临床安全性、有效性以及可操作性而申请临床试验。
In view of the inconvenience of most PRP preparation products on the market for the use of difficult-to-heal wounds, the research team of Hangzhou Yuancapsu Biotechnology Co., Ltd. has developed a molder product that can prepare PRP into concentrated PRP gel patches. As a former, the product prepares loose plasma gels into higher-strength plasma gel patches without changing the chemical structure and biological properties of PRP gels through physical extrusion. The product is simple to operate and has a short preparation time. Compared with the naturally formed PRP gel, the gel patch has stronger mechanical strength, and can be sutured with sutures with wound tissue, and can be cut at will according to the shape of the wound. The formed gel patch significantly prolonged the degradation time of the gel and increased the slow-release concentration and duration of growth factors. At present, this product has been inspected by the National Medical Products Administration (NMPA) certified inspection agency and concluded to be qualified, and has applied for clinical trials in order to further evaluate the clinical safety, efficacy and operability of the device.

临床试验目的
Clinical trial objectives

本研究的目的是验证杭州源囊生物科技有限公司委托浙江狄赛生物有限公司生产的研究一次性使用凝胶补片成型器临床操作使用的安全性和有效性。
The purpose of this study is to verify the safety and efficacy of the clinical operation of the research single-use gel patch former commissioned by Hangzhou Yuancapsu Biotechnology Co., Ltd. and produced by Zhejiang Disai Biotechnology Co., Ltd.

临床试验的实施
Implementation of clinical trials

试验流程图
Test flow chart

病例入组
Case enrollment

签署知情同意书（签名及日期），记录受试者基本信息，包括出生日期、性别、身高、体重、临床诊断和既往病史、过敏史等。记录入组前需要进行临床相关项目的检查结果。根据入选标准和排除标准选择合适的受试者。
Sign the informed consent form (signature and date), and record the subject's basic information, including date of birth, gender, height, weight, clinical diagnosis and past medical history, allergy history, etc. Record the results of the examination that need to be performed before enrollment. Appropriate subjects are selected according to the inclusion and exclusion criteria.

检查/检测项目
Inspection/Inspection Items

访视1：筛选期检查
Visit 1: Screening period examination

术前肝功能检查：谷丙转氨酶（ALT）、谷草转氨酶（AST）。
Preoperative liver function tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST).

术前肾功能检查：肌酐（CRE）、尿素氮（BUN）或尿素（UREA）。
Preoperative renal function tests: creatinine (CRE), urea nitrogen (BUN), or urea (UREA).

术前血常规检查：红细胞计数（RBC）、白细胞计数（WBC）、中性粒细胞比率（NEUT%）、淋巴细胞比率（LTMPH%）、血红蛋白浓度（HGB）、血小板计数（PLT）。
Preoperative blood routine examination: red blood cell count (RBC), white blood cell count (WBC), neutrophil ratio (NEUT%), lymphocyte ratio (LTMPH%), hemoglobin concentration (HGB). ), platelet count (PLT).

术前C反应蛋白检查。
Preoperative C-reactive protein test.

生命体征（体温、脉搏、呼吸、血压）。
Vital signs (temperature, pulse, respiration, blood pressure).

访视2：慢性溃疡修复术
Visit 2: Chronic ulcer repair

术前外周血抽取。
Preoperative peripheral blood draw.

清创术后创面分泌物细菌培养。
Bacterial culture of wound secretions after debridement.

术后产品使用性能评价。
Evaluation of product use performance after surgery.

访视3（术后3天内）：
Visit 3 (within 3 days after surgery):

创面分泌物细菌培养。
Bacterial culture of wound secretions.

血常规检查：红细胞计数（RBC）、白细胞计数（WBC）、中性粒细胞比率（NEUT%）、淋巴细胞比率（LTMPH%）、血红蛋白浓度（HGB）、血小板计数（PLT）。
Blood routine tests: red blood cell count (RBC), white blood cell count (WBC), neutrophil ratio (NEUT%), lymphocyte ratio (LTMPH%), hemoglobin concentration (HGB). ), platelet count (PLT).

肝功能检查：谷丙转氨酶（ALT）、谷草转氨酶（AST）。
Liver function tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST).

肾功能检查：肌酐（CRE）、尿素氮（BUN）或尿素（UREA）。
Renal function tests: creatinine (CRE), urea nitrogen (BUN), or urea (UREA).

术后C反应蛋白检查。
Postoperative C-reactive protein examination.

创面情况评估。
Wound assessment.

生命体征（体温、脉搏、呼吸、血压）。
Vital signs (temperature, pulse, respiration, blood pressure).

确认组别
Confirm the group

本试验根据随机原则确认受试者试验组别。
This trial identifies the trial group of subjects according to the principle of randomization.

受试者签署知情同意书后先给筛选号，筛选合格后给予受试者编号。
After the subjects sign the informed consent form, they will be given a screening number first, and the subject number will be given after passing the screening.

筛选号为S+2位数的试验中心编号+2位数的流水号组成，按照签署知情同意书时间给予筛选号，流水号不足2位时往前增加0补足2位。
The screening number is composed of S+2-digit test center number + 2-digit serial number, and the screening number is given according to the time of signing the informed consent form, and if the serial number is less than 2 digits, 0 is added forward to make up for 2 digits.

用统计软件编程，按中心分层，给定区组长度，按1:1比例将受试者分为试验组和对照组，产生至少38例受试者的随机分组安排，并制定相应的随机数字表。
Programmed with statistical software, stratified by center, given block length, subjects were divided into experimental and control groups in a 1:1 ratio, resulting in a randomization arrangement of at least 38 subjects, and a corresponding random number table was developed.

受试者编号为中心编号和流水号组成的四位数，前2位为试验中心编号，后2位为流水号，流水号不足2位时往前增加0补足2位。受试者入选后，研究者根据随机信封确认受试者组别，并采取相应组别的器械给受试者进行治疗。
The subject number is a four-digit number composed of the center number and the serial number, the first 2 digits are the test center number, the last 2 digits are the serial number, and if the serial number is less than 2 digits, 0 is added forward to make up for 2 digits. After the subjects are selected, the investigator confirms the subject group according to the random envelope and takes the corresponding group of devices for treatment.

试验器械操作步骤
Procedure of operation of the test instrument

手术当天术前，静脉抽取患者大概50-60mL外周血，尽量可采集到60mL。
On the day of surgery, about 50-60mL of peripheral blood was drawn from the patient's vein, and 60mL was collected as much as possible.

取其中约20mL外周血，对照组经150×g离心后获得上层血浆和血小板，转移至新的离心管中，再次800×g离心，弃去3/4的上清，下层混匀获得富血小板血浆。试验组进行相同的第一步离心操作，获得含血小板血浆备用。制备完成后于1-10℃保存，根据需要送至手术室。剩余血液用于检测血小板浓度、拉力和生长因子浓度。
About 20mL of peripheral blood were taken, and the control group was centrifuged at 150×g to obtain the upper layer of plasma and platelets, which were transferred to a new centrifuge tube for another 800 ×g centrifugation, discard 3/4 of the supernatant, and mix the lower layer to obtain platelet-rich plasma. The test group performed the same first step of centrifugation to obtain platelet-containing plasma for backup. After preparation, store at 1-10°C and send to the operating room as needed. The remaining blood is used to measure platelet concentration, tension, and growth factor concentration.

按照常规手术要求对创面部位进行消毒，充分切除坏死组织，彻底清创，直至健康出血的软组织完全暴露。根据文献报道，我们设计了针对清创治疗的评估表（表4《清创评估表》），研究者根据表进行打分，当三个维度分数均≥4分，且总分≥12分时，可认为清创完全，取创面处分泌送进行细菌培养检测。
The wound site is disinfected according to the requirements of routine surgery, the necrotic tissue is fully removed, and the debridement is thorough until the soft tissue with healthy bleeding is completely exposed. According to the literature report, we designed an evaluation form for debridement treatment (Table 4 "Debridement Evaluation Form"), according to which the researcher scored according to the table, and when the scores of all three dimensions ≥ 4 points, and the total score ≥ 12 points, the debridement can be considered complete, and the secretion from the wound surface can be sent for bacterial culture testing.

参考文献：
References:

Schultz, G., et al. Wound Bed Preparation: A Systematic Approach to Wound Management. Wounds International, 2003. Mar;11 Suppl 1:S1-28.
Schultz, G., et al. Wound Bed Preparation: A Systematic Approach to Wound Management. Wounds International, 2003. Mar; 11 Suppl 1:S1-28.

Falanga, V. Wound Healing and Its Impairment in the Diabetic Foot. The Lancet, 2005. Nov 12;366(9498):1736-43.
Falanga, V. Wound Healing and Its Impairment in the Diabetic Foot. The Lancet, 2005. Nov 12; 366(9498):1736-43.

Armstrong, D.G., et al. Debridement: The Key to Wound Healing. Podiatry Management, 2000. Dec;6(4):627-60.
Armstrong, D.G., et al. Debridement: The Key to Wound Healing. Podiatry Management, 2000. Dec; 6(4):627-60.

Wolcott, R.D., et al. "Biofilms and Chronic Wound Inflammation." Journal of Wound Care, 2008. Aug;17(8):333-41.
Wolcott, R.D., et al. "Biofilms and Chronic Wound Inflammation." Journal of Wound Care, 2008. Aug; 17(8):333-41.

对照组在富血小板血浆中以1:10的体积加入凝血酶，静置3分钟后形成凝胶。其中对照组用无菌镊子轻轻夹取凝胶敷于创面处。
The control group added thrombin in platelet-rich plasma at a volume of 1:10 and left for 3 minutes to form a gel. The control group used sterile forceps to gently pick up the gel and apply it to the wound.

试验组按器械操作说明书将血浆和凝血酶注入成型器中，挤压形成凝胶补片，用无菌镊子轻轻夹取凝胶敷于创面处。
The experimental group injected plasma and thrombin into the molding device according to the instrument operation manual, squeezed to form a gel patch, and gently picked up the gel with sterile forceps and applied it to the wound.

若手术中有特殊需要，可在无菌条件下对凝胶补片进行适当裁剪，并根据需要将补片与软组织进行缝合固定。
If there is a special need for surgery, the gel patch can be cut appropriately under sterile conditions, and the patch can be sutured and fixed with the soft tissue as needed.

按照常规手术要求缝合创面并用敷料覆盖包扎。
The wound is sutured and covered with a dressing according to the requirements of the routine operation.

受试者选择
Subject selection

入选标准
Selection criteria

可以加入本试验的受试者，必须符合下述所有条件：
Subjects eligible for this trial must meet all of the following criteria:

18周岁-75周岁；
18-75 years old;

需进行清创修复的慢性创面患者；
Patients with chronic wounds requiring debridement repair;

伤口持续时间＞4周；
Wound duration> 4 weeks;

自愿参加本研究，并签署知情同意书；
Volunteer to participate in this study and sign the informed consent form;

排除标准
Exclusion Criteria  

如遇下列任何情况之一，受试者不应参加试验：
Subjects should not participate in the trial if any of the following conditions occur:

重度血小板减少症、败血症的患者；
Patients with severe thrombocytopenia and sepsis;

对橡胶成分过敏患者；
Patients who are allergic to rubber ingredients;

1月内注射过糖皮质激素、或2周内进行全身皮质激素治疗的患者；
Patients who have been injected with glucocorticoids within 1 month or systemic corticosteroid therapy within 2 weeks;

恶性肿瘤患者；
Patients with malignant tumors;

血红蛋白＜100g/L，血小板计数＜100×10⁹/L；
Hemoglobin < 100g/L, platelet count < 100×10⁹/L ；

精神疾病者、认知损伤者、危重患者、未成年人、孕妇；
Mental illness, cognitive impairment, critically ill patients, minors, and pregnant women;

3个月内参加过或正在参加药物临床试验，或 30天内参加过或正在参加其他医疗器械临床试验者；
Those who have participated in or are participating in drug clinical trials within 3 months, or have participated in or are participating in other medical device clinical trials within 30 days;

研究者认为不宜参与研究的其他情况。
Other conditions that the investigator deems unsuitable for participation in the study.

受试者退出标准
Subject withdrawal criteria

受试者自行退出
Subjects withdraw on their own

无论何种原因，受试者不愿意或不可能继续进行临床试验，向研究者提出退出临床试验的要求而终止临床试验者；
Regardless of the reason, the subject is unwilling or unable to continue the clinical trial, and the clinical trial is terminated by requesting the investigator to withdraw from the clinical trial;

受试者虽未明确提出退出临床试验，但不再接受治疗及检查而失访者。
Although the subjects did not explicitly propose to withdraw from the clinical trial, they no longer received treatment and examination and were lost to follow-up.

研究者决定退出
The researcher decided to withdraw

受试者出现过敏反应或严重不良事件（Serious Adverse Event，SAE），且无法完成后续的试验，根据研究者判断应终止临床试验；
Subjects with allergic reactions or serious adverse events (SAEs) and unable to complete subsequent trials, the clinical trial should be terminated according to the investigator's judgment;

临床试验过程中，受试者发生其他并发症，不宜继续接受临床试验；
During the clinical trial, the subject has other complications and is not suitable to continue to undergo the clinical trial;

受试者不符合试验的入选标准、符合排除标准而被错误入选，且未使用试验器械；
Subjects who do not meet the inclusion criteria of the trial, are wrongly selected due to meeting the exclusion criteria, and do not use the test device;

临床试验过程中该受试者出现严重的方案偏离，如试验过程中使用非本方案中规定器械，或中途用非规定范围内联合用药，以无法对其临床试验结果进行有效评价；
During the clinical trial, the subject has serious protocol deviations, such as using devices other than those specified in this protocol during the trial, or using drugs not within the specified range in the middle of the trial, so that the clinical trial results cannot be effectively evaluated;

受试者依从性差。
Poor subject compliance.

受试者试验终止后，研究者应该从保障受试者权益的角度，继续为受试者提供适当的治疗，并详细告知受试者在其试验期间所接受的治疗及相关处理。受试者的相关数据依旧可以用于评价产品的安全性。研究者应将受试者试验终止的情况及时反馈给申办方。
After the termination of the subject's trial, the investigator should continue to provide appropriate treatment to the subject from the perspective of protecting the rights and interests of the subject, and inform the subject in detail of the treatment and related treatment received during the trial. Data from subjects can still be used to evaluate the safety of the product. The investigator should promptly feedback the termination of the subject's trial to the sponsor.

临床试验样本量
Clinical trial sample size

本试验主要评价指标为经一次性使用凝胶补片成型器制备的血小板凝胶补片中血小板浓度优于相同条件下制备的富血小板血浆中血小板浓度。因此本试验根据公式：
The main evaluation index of this trial was that the platelet concentration in platelet gel patches prepared by a disposable gel patch molder was better than that in platelet-rich plasma prepared under the same conditions. Therefore, this trial is based on the formula:

其中α=0.05，β=0.2。PC和PT为对照组和试验组血小板浓度符设定合阈值的成功率， 为PC和PT的差值绝对值，∆为优效界值，取正值。
where α=0.05, β=0.2. PC and PT set thresholds for the platelet concentration symbols of the control group and the test group, which were PC and PT The absolute value of the difference is ∆ the efficiency threshold, and the positive value is taken.

根据临床实际情况，此处PC为15%，PT为65%，∆=0.1。
According to the clinical situation, PC is 15%, PT is 65%, ∆=0.1.

代入公式得，N=36。
The substitution formula yields , N=36.

按照统计学要求，此次临床试验共选合格病例36例才具有统计学意义。按照5%的脱落率计算，最终需要入选病例38例。
According to statistical requirements, a total of 36 qualified cases were selected for this clinical trial to be statistically significant. According to the 5% dropout rate, 38 cases need to be selected in the end.

试验医疗器械
Experiment with medical devices

试验组
Experimental group

采集外周血液，清创术后，采用经一次性使用凝胶补片成型器制备的PRP凝胶补片敷于创面。剩余血液用于PRP凝胶和凝胶补片的性能检测。
Peripheral blood was collected, and after debridement, PRP gel patches prepared by a disposable gel patch former were applied to the wound surface. Remaining blood is used for performance testing of PRP gels and gel patches.

对照组
Control group

采集外周血液，清创术后，采用PRP凝胶敷于创面。剩余血液用于PRP凝胶和凝胶补片的性能检测。
Peripheral blood was collected, and after debridement, PRP gel was applied to the wound surface. Remaining blood is used for performance testing of PRP gels and gel patches.

临床评价标准
Clinical evaluation criteria

有效性评价
Effectiveness evaluation

主要评价指标
Main evaluation indicators

主要评价指标为血小板浓度合格率。
The main evaluation index was the qualified rate of platelet concentration.

评价方法：测试PRP和通过产品制备的凝胶补片中的血小板浓度。
Evaluation methods: Platelet concentrations in PRP and gel patches prepared by the product were tested.

取抗凝外周血（约20mL，平均分为富血小板血浆（PRP）组和凝胶补片（补片）组），PRP组经150×g离心10分钟后获得上层血浆和血小板，将10mL含血小板血浆转移至新的离心管中，再次800×g离心5分钟，弃去约3/4的上清，下层混匀获得富血小板血浆，测量血小板浓度记为。
Anticoagulant peripheral blood (about 20mL, evenly divided into platelet-rich plasma (PRP) group and gel patch (patch) group) was collected, and the PRP group was 150 ×g centrifugation 1 0 min to obtain the upper layer of plasma and platelets, transfer 10 mL of platelet-containing plasma to a new centrifuge tube, and centrifuge again at 800×g For 5 minutes, discard about 3/4 of the supernatant, mix the lower layer well to obtain platelet-rich plasma, and measure the platelet concentration as .

补片组经150×g离心10分钟后获得上层血浆和血小板，测量血小板血浆体积和血小板浓度。根据产品说明书，将血小板血浆和1/10体积的凝血酶在一次性凝胶补片成型器中混匀，然后挤压加工成凝胶补片。保留滤出液体，测得滤出液体积和血小板浓度。
The upper layer of plasma and platelets were obtained after centrifugation of 150×g for 10 minutes, and the platelet plasma volume and platelet concentration were measured. According to the product manual, platelet plasma and 1/10 volume of thrombin are mixed in a disposable gel patch former and then extruded into a gel patch. The leachate liquid was retained, and the volume of the leachate fluid and platelet concentration were measured.

测量并根据公式计算各组的血小板浓度。
Platelet concentrations in each group were measured and calculated according to the formula.

记录时间：PRP凝胶补片制备完成后3小时内。
Recording time: within 3 hours after the preparation of PRP gel patches.

分析方法：根据评价方法制备样品并测量，根据下列公式计算凝胶补片中血小板浓度。
Analysis method: Prepare the sample according to the evaluation method and measure it, and calculate the platelet concentration in the gel patch according to the following formula.

根据患者V1访视的血常规血小板浓度，根据下列公式计算对照组和试验组血小板的富集倍数N：
According to the blood routine platelet concentration of the patient V1 visit, the enrichment factor N of platelets in the control group and the test group was calculated according to the following formula:

对照组： 试验组：
Control group: Experimental group:

若富集倍数处于2-8倍区间内，则认为合格。
If the enrichment multiple is in the range of 2-8 times, it is considered qualified.

计算两组血小板浓度的合格率并进行优效性检验
The pass rate of platelet concentration in the two groups was calculated and the superiority test was performed

次要评价指标
Secondary evaluation indicators

次要评价指标1：术后3天创面细菌情况。
Secondary evaluation indicator 1: Wound bacteria 3 days after surgery.

评价方法：术中清创术结束和术后3天，由研究者取对照组和试验组创面部位分泌物进行细菌培养检查。
Evaluation methods: At the end of intraoperative debridement and 3 days after surgery, the investigator took the secretions from the wound site of the control group and the experimental group for bacterial culture examination.

记录时间：术中（清创术结束）和术后3天。
Recording time: intraoperative (end of debridement) and 3 days postoperatively.

析方法：根据表2，对两组创面细菌情况进行评分，并在两组间对评分结果进行组间差异性分析。
Analysis methods: According to Table 2, the bacterial situation of the wound in the two groups was scored, and the difference between the two groups was analyzed.

次要评价指标2：生长因子浓度。
Secondary evaluation index 2: growth factor concentration.

评价方法：取约20mL抗凝外周血，平均分为PRP组和补片组。PRP组经150×g离心10分钟后获得上层血浆和血小板，将含血小板血浆转移至新的离心管中，再次800×g离心5分钟，弃去3/4的上清，下层混匀获得富血小板血浆，加入1/10体积的凝血酶成胶后放入50mL离心管中，加入4倍体积的生理盐水37℃浸提1小时。
Evaluation methods: Approximately 20mL of anticoagulant peripheral blood was collected, and it was evenly divided into PRP group and patch group. The upper layer of plasma and platelets were obtained after centrifugation at 150×g for 10 minutes, and the platelet-containing plasma was transferred to a new centrifuge tube againCentrifuge 800×g for 5 minutes, discard 3/4 of the supernatant, mix the lower layer well to obtain platelet-rich plasma, add 1/10 volume of thrombin to form a gel and put in 50 In a mL centrifuge tube, add 4 times the volume of normal saline at 37°C for 1 hour.

补片组经150×g离心10分钟后获得含血小板血浆，根据产品说明书，将含血小板血浆和1/10体积的凝血酶在一次性凝胶补片成型器中混匀，然后挤压加工成凝胶补片，将补片放入50mL离心管中，加入4倍体积的生理盐水37℃浸提1小时。浸提结束后，取出凝胶和凝胶补片，用ELISA试剂盒检测PDGF-BB、TGF-β1和IL-1β三个因子的浓度。
According to the product manual, platelet-containing plasma and 1/10 volume of thrombin were mixed in a disposable gel patch former, and then extruded into gel patches.× Place the patch in a 50mL centrifuge tube and add 4 times the volume of normal saline to 37 °C for 1 h. After the extraction, the gel and gel patch were removed, and the concentrations of PDGF-BB, TGF-β1 and IL-1β were detected with the ELISA kit.

记录时间：PRP凝胶和凝胶补片制备完成后12小时内。
Recording time: within 12 hours after the preparation of PRP gel and gel patch is completed.

分析方法：根据评价方法检测PRP凝胶和凝胶补片释放的生长因子浓度，并进行组间差异分析。
Analysis methods: The concentration of growth factors released by PRP gel and gel patch was detected according to the evaluation method, and the difference analysis between groups was carried out.

次要评价指标3：极限拉力强度。
Secondary evaluation index 3: ultimate tensile strength.

评价方法：取血小板浓度检测试验的剩余富血小板血浆（PRP组）和凝胶补片（补片组）进行拉力强度检测。
Evaluation methods: The remaining platelet-rich plasma (PRP group) and gel patch (patch group) were taken for tensile strength testing.

PRP组将1.8mL富血小板血浆和1/10体积的的凝血酶加入φ35mm的圆饼型培养皿中成胶。
In the PRP group, 1.8mL of platelet-rich plasma and 1/10 volume of thrombin were added to φ35 mm round cake dish to form a gel.

将PRP组凝胶和补片组凝胶补片用手持式拉力计检测凝胶能承受的最大拉力。
The maximum tensile force that the gel can withstand is tested with a handheld tensile meter.

记录时间：PRP凝胶和凝胶补片制备完成后3小时内。
Recording time: within 3 hours after the preparation of PRP gel and gel patch is completed.

分析方法：根据评价方法记录PRP凝胶和凝胶补片的最大极限拉力，并进行组间差异分析，以验证产品增强凝胶拉力的有效性。
Analysis methods: The maximum ultimate tensile force of PRP gel and gel patch was recorded according to the evaluation method, and the difference analysis between groups was performed to verify the effectiveness of the product in enhancing the gel tensile force.

次要评价指标4：术后伤口情况
Secondary evaluation criterion 4: postoperative wound condition

评价方法：术后3天，研究者按照《表3伤口评估表》对受试者伤口进行打分，以评估伤口感染情况。《伤口评估表》如下：
Evaluation method: 3 days after surgery, the investigator scored the wound of the subjects according to the "Table 3 Wound Assessment Form" to evaluate the wound infection. The Wound Assessment Form is as follows:

参考文献：
References:

Armstrong DG., et al. Diabetic Foot Ulcers: A Review. JAMA. 2023. Jul; 3;330(1):62-75.
Armstrong DG., et al. Diabetic Foot Ulcers: A Review. JAMA. 2023. Jul; 3; 330(1):62-75.

记录时间：术后3天。
Recording time: 3 days postoperatively.

分析方法：根据评价方法检测对照组和试验组术后3天创面情况进行打分，进行组间差异性分析。
Analysis method: According to the evaluation method, the wound conditions of the control group and the test group were scored 3 days after surgery, and the difference between the groups was analyzed.

次要评价指标5：产品使用性能
Secondary evaluation indicator 5: product use performance

评价方法：术后由手术研究者对试验器械进行使用性能评价，评价内容如下：
Evaluation method: The performance of the test instrument was evaluated by the surgical investigator after surgery, and the evaluation content was as follows:

产品性能、操作过程、制备性能三个维度中，每个维度至少有1项评价为“是”，并且上述12项评价内容至少9项评价为“是”，使用性能评价为“满意”；否则，使用性能评价为“不满意”。
Among the three dimensions of product performance, operation process, and preparation performance, at least one evaluation in each dimension is "yes", and at least 9 of the above 12 evaluation contents are rated as "yes", and the performance evaluation is "satisfactory". Otherwise, the performance of the use is rated as "unsatisfactory".

记录时间：手术完成当天。
Recording time: The day the surgery is completed.

分析方法：根据评价方法及下列公式，统计试验器械使用性能满意度。
Analysis method: According to the evaluation method and the following formula, the satisfaction of the performance of the test instrument is counted.

次要评价指标6：血小板浓度
Secondary evaluation indicator 6: platelet concentration

评价方法：根据主要评价指标中测量计算结果获得PRP组和补片组血小板浓度。进行组间差异性分析。
Evaluation methods: The platelet concentrations of P RP group and patch group were obtained according to the measurement and calculation results in the main evaluation indicators. Analysis of differences between groups was performed.

记录时间：PRP凝胶补片制备完成后3小时内。
Recording time: within 3 hours after the preparation of PRP gel patches.

分析方法：对PRP组和补片组的血小板浓度进行组间差异性分析。
Analysis methods: The platelet concentrations of PRP group and patch group were analyzed between groups.

安全性评价
Safety evaluation

安全性评价指标：实验室检查异常情况、生命体征检查情况、不良事件和严重不良事件发生情况。
Safety evaluation indicators: abnormal laboratory examination, vital sign examination, adverse events and serious adverse events.

安全性评价指标1：实验室检查异常情况
Safety evaluation index 1: Abnormal laboratory examination

评价方法：术后3天复查血常规、肝功能、肾功能，记录血常规中红细胞计数（RBC）、白细胞计数（WBC）、中性粒细胞比率（NEUT%）、血红蛋白浓度（HGB）、血小板计数（PLT）检查结果；记录肝功能中谷草转氨酶（AST）、谷丙转氨酶（ALT）检查结果；记录肾功能中肌酐（CRE）、尿素氮（BUN）或尿素（UREA）检查结果。记录血液C反应蛋白结果。如果检查结果正常或异常但无临床意义，则判定结果正常，如果检查结果异常有临床意义，则按照异常结果处理。
Evaluation methods: Blood routine, liver function, and kidney function were reviewed 3 days after surgery, and red blood cell count (RBC), white blood cell count (WBC), neutrophil ratio (NEUT%), and hemoglobin concentration () were recorded in blood routine HGB), platelet count (PLT) test results; The results of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in liver function were recorded. The results of creatinine (CRE), urea nitrogen (BUN) or urea (UREA) tests in renal function were recorded. Record blood C-reactive protein results. If the test results are normal or abnormal but not clinically significant, the results are judged to be normal, and if the test results are abnormal and clinically significant, they are treated as abnormal results.

记录时间：术后3天。
Recording time: 3 days postoperatively.

分析方法：根据评价方法及下列公式计算实验室检查异常情况。
Analysis method: Calculate laboratory abnormalities according to the evaluation method and the following formula.

安全性评价指标2：生命体征检查情况
Safety evaluation index 2: vital sign examination

评价方法：术后3天复查基本生命体征，记录体温、脉搏、呼吸、血压。
Evaluation methods: Basic vital signs were reviewed 3 days after surgery, and body temperature, pulse, respiration, and blood pressure were recorded.

记录时间：术后3天。
Recording time: 3 days postoperatively.

分析方法：根据评价方法，记录试验组和对照组术后3天的生命体征，进行组间差异性分析。
Analysis method: According to the evaluation method, the vital signs of the experimental group and the control group were recorded 3 days after surgery, and the difference between groups was analyzed.

安全性评价指标3：不良事件和严重不良事件发生情况
Safety evaluation index 3: occurrence of adverse events and serious adverse events

评价方法：试验过程中出现的任何不利的医学事件，无论是否与器械有关，均为不良事件。如果临床试验过程中发生导致死亡或者健康状况严重恶化的事件，则判定为严重不良事件。所有不良事件和严重不良事件均需判定是否与受试器械有关。不良事件和严重不良事件与受试器械的关系，分为“肯定有关”、“很可能有关”、“可能有关”、“可能无关”、“无关”，通过不良事件、严重不良事件发生率和与器械相关的不良事件、严重不良事件反映受试器械的安全性。
Evaluation methodology: Any adverse medical event during the trial, whether or not device-related, is an adverse event. Serious adverse events are determined if they occur during the course of a clinical trial that result in death or serious deterioration of health. All adverse events and serious adverse events should be determined to be related to the test device. The relationship between adverse events and serious adverse events and the test device is divided into "definitely related", "likely related", "possibly related", "possibly unrelated", "not related", and divided into adverse events, serious adverse events and device-related adverse events, Serious adverse events reflect the safety of the test device.

试验器械预期的不良事件包括：器械缺陷、伤口不适、创面感染等。
Expected adverse events of the test device include: device defects, wound discomfort, wound infection, etc.

器械缺陷情况：指术中是否存在器械包装破损、器械破损等功能故障的事件发生。
Device defects: refers to whether there are functional failures such as broken device packaging and equipment damage during surgery.

伤口不适情况：指术后是存在伤口剧烈疼痛、麻木、瘙痒的事件发生。
Wound discomfort: refers to the occurrence of severe pain, numbness, and itching in the wound after surgery.

创面感染情况：指术后是否发生创面感染事件发生。
Wound infection: refers to whether wound infection occurs after surgery.

注：与临床诊断和既往基础疾病相关的病情（以基线检查或既往病史为准），如果严重程度和治疗方法没有改变，可不作为不良事件报告。
Note: Conditions related to clinical diagnosis and previous underlying disease (based on baseline examination or past medical history) may not be reported as adverse events if the severity and treatment do not change.

记录时间：从受试者确定入组到术后3天出组。
Recording time: From the time the subject is confirmed to enroll to the group 3 days after surgery.

分析方法：根据评价方法记录试验过程中发生的不良事件和严重不良事件，根据下列公式计算不良事件及严重不良事件发生率，并进行组间差异性分析。
Analysis methods: Adverse events and serious adverse events that occurred during the trial were recorded according to the evaluation method, and the incidence of adverse events and serious adverse events was calculated according to the following formula, and the difference analysis between groups was carried out.

统计分析方法
Statistical analysis methods

分析数据集
Analyze the dataset

全分析集（FAS）：全分析集为尽可能接近于包括所有随机化的受试者的分析集，通常应包括所有入组且使用过一次器械/接受过一次治疗的受试者，只有在非常有限的情形下才可剔除受试者，包括违反了重要的入组标准、入组后无任何观察数据的情形。
Full Analysis Set (FAS): A full analysis set is as close as possible to include all randomized subjects and should generally include all enrolled subjects who have used a device/received a single treatment, and only in very limited cases can exclude subjects, including cases where important enrollment criteria have been violated and there is no observational data after enrollment.

符合方案集（PPS）：符合方案集是全分析集的子集，包括已接受方案中规定的治疗、可获得主要评价指标的观察数据、对试验方案没有重大违背的受试者。
Conformance set (PPS): Conformance set is a subset of the full analysis set, including subjects who have received the treatment specified in the protocol, have observed data for the primary endpoint, and have no significant violations of the trial protocol.

安全分析集（SS）：安全性数据集通常应包括所有入组且使用过一次器械/接受过一次治疗并进行过安全性评价的受试者。
Safety Analysis Set (SS): The safety dataset should generally include all enrolled subjects who have used a device/treatment once and have undergone a safety evaluation.

备注：若从全分析集和符合方案集中剔除受试者，一是需符合方案中的定义，二是需充分阐明剔除理由，需在盲态审核时阐明剔除理由。
Note: If subjects are excluded from the full analysis set and the conformance set, one must meet the definition in the protocol, and the other must fully explain the reason for exclusion, and the reason for exclusion must be clarified during the blind review.

受试者剔除标准
Subject Exclusion Criteria

出现以下三种情况，需在数据审核阶段讨论后决定是否剔除。
In the following three situations, it is necessary to decide whether to remove them after discussion in the data review stage.

不符合入选标准的受试者；
Subjects who do not meet the inclusion criteria;

符合排除标准的受试者；
Subjects who meet the exclusion criteria;

违背/偏离方案的受试者。
Subjects who violate/deviate from the protocol.

统计分析方法
Statistical analysis methods

统计软件：采用SPSS 29统计分析软件。
Statistical software: SPSS 29 statistical analysis software was used.

基本原则：所有的统计检验均采用双侧检验，P值小于或等于0.05将被认为所检验的差别有统计学意义。
Basic principle: All statistical tests are two-tailed tests, and a P value of less than or equal to 0.05 will be considered to be statistically significant for the difference tested.

定量指标的描述将计算均数、标准差、中位数、最小值、最大值。
The description of the quantitative indicator will calculate the mean, standard deviation, median, minimum, maximum.

分类指标的描述用各类的例数及百分数。
The description of classification indicators uses the number of examples and percentages of various categories.

统计分析应至少包括如下几个部分：
Statistical analysis should include at least the following parts:

a、临床试验完成情况描述：包括临床试验概况（入组人数、完成人数、失访/退出/剔除人数等），列出未完成病例及未进入各人群病例的清单；
a. Description of clinical trial completion: including the overview of clinical trials (number of enrolled, completed, number of people lost to follow-up/withdrawn/eliminated, etc.), and list of incomplete cases and cases that have not entered each population;

b、基线描述：应对基线人口统计学指标及其他相关病史指标等进行描述；计量资料符合正态性及方差齐性者采用t检验，不符合正态性者采用非参数检验，符合正态性不符合方差齐性者采用校正t检验。
b. Baseline description: Baseline demographic indicators and other relevant medical history indicators should be described; The t-test was used for the normality and homogeneity of variance, the non-parametric test was used for the non-normality test, and the corrected t-test was used for the normality but not the homogeneity of variance.

c、效果评价：有效性分析时，除点估计外，还应给出点估计的95%的可信区间，并将总体率差值95%置信区间下限与方案中预先指明的优效界值进行比较，判断受试器械是否满足优效假设。
c. Effect evaluation: In addition to the point estimate, the 95% confidence interval of the point estimate should be given, and the lower limit of the 95% confidence interval of the overall rate difference should be compared with the pre-specified superior threshold in the scheme to determine whether the test device is satisfied Superior hypothesis.

统计评价方法
Statistical evaluation methods

有效性评价
Effectiveness evaluation

主要评价指标采用置信区间法进行优效检验，统计试验组和对照组血小板浓度合格率，计算试验组-对照组置信区间的下限C_L，若[C_L , ∞] 完全在[ ∆, ∞] 范围内，或者C_L > ∆，可下优效性的结论。
The main evaluation index was performed by the confidence interval method, the pass rate of platelet concentration in the experimental group and the control group was counted, and the lower limit of the confidence interval between the experimental group and the control group was calculated , ∞] is completely within the range of [ ∆, ∞], or C_L > ∆, and the conclusion of superiority can be drawn。

次要评价指标采用差异性检验，计量资料符合正态性及方差齐性者采用t检验，不符合正态性者采用非参数检验，符合正态性不符合方差齐性者采用校正t检验。计数资料采用χ²检验或Fisher exact检验。
The difference test was used for the secondary evaluation indicators, the t-test was used for the normality and variance homogeneity of the measurement data, the non-parametric test was used for the non-normality test, and the corrected t-test was used for the normality but not the homogeneity of variance. The chi-square^test or Fisher exact test was used for counting.

安全性评价
Safety evaluation

安全性指标采用差异性检验，计量资料符合正态性及方差齐性者采用t检验，不符合正态性者采用非参数检验，符合正态性不符合方差齐性者采用校正t检验。计数资料采用χ²检验或Fisher exact检验。
The safety index was tested by difference, the t-test was used for the normality and homogeneity of the variance, the non-parametric test was used for the non-parametric test that did not conform to the normality, and the corrected t-test was used for the normality but not the homogeneity of variance. The chi-square^test or Fisher exact test was used for counting.

缺失值和异常值的处理
Handling of missing and outliers

所有缺失、未用或错误数据（包括中途退出和撤出）和不合理数据，由研究者及生物统计师共同商讨，并最终确定。这些数据处理的统计学基本原则如下：
All missing, unused, or erroneous data (including withdrawals and withdrawals) and unreasonable data shall be discussed and finalized by researchers and biostatisticians. The basic statistical principles for the processing of these data are as follows:

描述脱落的每一位受试者的详细情况；
Describe the details of each subject who drops out;

基线的缺失数据，可以不进行估计；
Missing data from baseline can be estimated without estimation;

对错误、不合理的数据可当缺失值处理；
Wrong and unreasonable data can be treated as missing values;

对所有安全性指标的缺失值不进行估计。
Missing values for all safety indicators are not estimated.

临床试验结果
Clinical trial results

分析数据集
Analyze the dataset

入组病例及安全性分析人群
Enrolled cases and safety analysis population

本试验共筛选41例受试者，筛选失败1例，筛选期退出2例，最后成功入组38例。纳入FAS分析集38例，符合方案集（PPS）38例，安全分析集（SS）37例，每个分析集病例数均达到统计学要求的36例。
A total of 41 subjects were screened in this trial, 1 case failed screening, 2 cases withdrew from the screening period, and finally 38 cases were successfully enrolled. Thirty-eight cases were included in the FAS analysis set, 38 cases in accordance with the protocol set (PPS), and 37 cases in the safety analysis set (SS).The number of cases in each analysis set reached the statistical requirement of 36.

表4 入组病例基本情况
Table 4 Basic information of enrolled cases

表5 安全性和有效性分析人群
Table 5 Safety and efficacy analysis population

脱落、剔除、方案偏离病例详情
Dropouts, exclusions, deviations from the protocol Details of the case

综合分析38例受试者的数据，共有30例受试者发生方案偏离。其中，1例受试者失访，影响安全性评价指标的结果，不影响主要评价指标和大部分次要评价指标结果，属于轻度偏离，未纳入安全分析集（SS）。
The data of 38 subjects were comprehensively analyzed, and a total of 30 subjects deviated from the protocol. Among them, 1 subject was lost to follow-up, which affected the results of the safety evaluation index and did not affect the results of the primary evaluation index and most of the secondary evaluation indicators, which was a slight deviation and was not included in the safety analysis set (SS).

此外，其余受试者均发生轻度偏离，因不影响主要有效性指标和次要有效性指标的评价，纳入全分析集（FAS）、符合方案集（PPS）和安全分析集（SS）。
In addition, the remaining subjects had mild deviations, and because they did not affect the evaluation of the primary and secondary effectiveness indicators, they were included in the full analysis set (FAS), conformity set (PPS), and safety analysis set (SS).

具体脱落、剔除、方案偏离病例详情结果见下表。
The details of the cases of dropout, exclusion, and deviation from the protocol are shown in the table below.

表6 受试者脱落、剔除、方案偏离清单
Table 6 List of subjects dropped out, eliminated, and deviated from the protocol