A Study on 3D Printing-assisted Platelet-rich Plasma Combined With Autologous Periosteum-bone Grafting in the Treatment of Knee Cartilage Injury
Phase: NA
Conditions: Osteochondral Lesions of Knee, Osteo Arthritis
Sponsor: Second Affiliated Hospital of Nanchang University

Clinical research plan approval 
Title: A study on 3D printing-assisted platelet-rich plasma 
combined with autologous periosteum-bone grafting in the 
treatment of knee cartilage injury 
Study type: Prospective randomized controlled study 
Funding source: The Second Affiliated Hospital of Nanchang 
University  
Study Duration: January 2026 - December 2029 
Date of the documen: September 28, 2025 
Project leader: Fu Xiaoling Telephone: 18679102713 
Research unit: The Second Affiliated Hospital of Nanchang University 
Team leader unit: The Second Affiliated Hospital of Nanchang 
University 
Participating unit: The Second Affiliated Medical College of 
Nanchang University 
 
 

Team members 
numb 
ering 
name 
job title 
specialized 
Division 
GCP certificate 
number 
signature
1 
Fu 
Xiaolin g 
Deputy 
Chief 
Physician 
Orthopedi 
cs 
Tissue test to confirm SAE; 
EFY-2021-763 
2 
Zhou 
Bin 
Deputy 
Chief 
Physician 
Orthopedi 
cs 
Professional group quality 
controller 
EFY-2023GCP- 
026 
3 
Tao Jun 
Chief 
physician 
Orthopedi 
cs 
screening patients, talking 
about informed consent, and 
managing patients; 
EFY-GCP- 
2024-234 
4 
Hao 
Liang 
Chief 
physician 
Orthopedi 
cs 
screening patients, talking 
about informed consent, and 
managing patients; 
GCP2111Y06- 
280 
5 
Sun Kuo 
Chief 
physician 
Orthopedi 
cs 
screening patients, talking 
about informed consent, and 
managing patients; 
 
6 
Peng 
Kun 
Deputy 
Chief 
Physician 
Orthopedi 
cs 
screening patients, talking 
about informed consent, and 
managing patients; 
EFY-2021-784 
7 
Deng 
Jianjian 
Attending 
Orthopedi 
cs 
screening patients, talking 
about informed consent, and 
managing patients; 
FY-2021IT- 098 
8 
Chen Qi 
sharp 
Resident 
Orthopedi 
cs 
screening patients, talking 
about informed consent, and 
managing patients; Fill out 
the CRF form 
Not at the 
moment 
9 
Cai 
Shengh 
ao 
Resident 
Orthopedi 
cs 
screening patients, talking 
about informed consent, and 
managing patients; Follow 
Not at the 
moment 
10 
Xia Yong Resident 
Orthopedi 
screening patients, talking 
about informed consent, and 
Not at the 

cs 
managing patients; Data 
management 
moment 
11 
Zheng 
Zuorui 
Resident 
Orthopedi 
cs 
Fill out the CRF form; Follow-
up 
Not at the 
moment 
12 
WALEE 
D 
KHALID 
Resident 
 
Orthopedi 
cs 
Fill out the CRF form; Data 
management 
 
Not at the 
moment 
 
 
 

Summary of the study protocol 
It should include the research topic, research purpose, design type, research object, 
sample size, selection criteria, observation indicators, statistical analysis methods, etc 
Research Title: 
A study on 3D printing-assisted platelet-rich plasma combined with autologous 
periosteum-bone grafting in the treatment of knee cartilage injury 
Objectives: 
(1) To evaluate the accuracy of cartilage damage repair by measuring the chimerism and 
surface curvature matching degree of 3D printing reconstruction. 
(2) The functional and imaging scores of 3D printing-assisted platelerichplasma (PRP) 
combined with autologous periosteum-bone grafting in the treatment of knee cartilage 
injury were performed to evaluate the clinical effect and cartilage 
repair effect. 
Design Type: 
Prospective randomized controlled trial Research Objects: 
The area of cartilage injury in the unilateral knee joint was >2CM2, and the patients were 
classified as grade 3-4 by the International Cartilagerepair Society (ICRS). 
Sample size: 60 cases (30 patients with 3D printing-assisted autoperiosteal-bone grafting, 
30 patients with 3D printing-assisted PRP combined with autologous periosteum-bone 
grafting) 
Selection Criteria: 
(1) Age 18~65 years old;  
(2) bodymass index (BMI) of 18~30kg/m2;  
(3) Knee cartilage injury confirmed by imaging examination, knee cartilage injury 2>cm2, 
ICRS grade 3-4;  
(4) There is no obvious abnormality in the lower limb force line; 
(5) No other drug injection or surgical treatment has been performed locally in the knee 
joint in the past 1 year. 
Observation indicators: 
(1) Clinical function: Lysholm score, Tegner exercise ability score, and pain numeric score 

of the knee joint were obtained by outpatient follow-up before surgery and 1, 3, 6, and 
12 months after surgery, written questionnaires, or by trained medical professionals over 
the phone to evaluate the patient's symptoms and functional improvement.  
(2) Imaging evaluation: Bilateral knee MRI examination was performed on the second day 
after surgery, and the anatomical reconstruction was evaluated by mirror technology, 
including the chimerism of the bone bone interface between the graft and the host bone, 
and the match of the surface curvature of the graft and the recipient area. An orthopedic 
surgeon and an experienced imaging center doctor used the magnetic resonance 
observation of cartilage repair tissue (MOCART) scoring method to evaluate cartilage 
repair before surgery and 1 year after surgery. 
Statistical analysis methods: 
SPSS software was used for data analysis. The continuous data were expressed by (i±s), 
and the normality test was performed, and the SNK test was used for comparison 
between groups. Repeated measures analysis of variance was used for comparison of 
time data before and after intervention within the group, and paired sample f test was 
used for comparison at two time points. If the data does not meet the normal distribution, 
the logarithmic transformation is analyzed again. The X2 test was used for the counting 
data. P<0.05 was a statistically significant difference. 
Background information on the study 
The background and significance of the research are described in detail, the current status 
of domestic and foreign research is described, the progress and shortcomings of the 
research field are systematically reviewed, and the basis for the research project is 
expounded. The references cited should be marked in the background information. 
Knee cartilage injury is a common refractory joint disease in athletes and the general 
population. An epidemiological investigation showed that cartilage damage accounted 
for 63% of knee arthroscopic surgeries1. Articular cartilage is a non-vascular, nerve-free 
and lymphatic tissue, which is difficult to repair after cartilage damage, and also affects 
the subchondral bone2, and the lesion of the subchondral bone will further aggravate 
cartilage damage, lead to cartilage detachment, accelerate the progression of 
osteoarthritis, seriously affect joint function, and have a high disability rate and 
teratogenicity. The treatment of cartilage injury is still a key issue and a major challenge 
in the field of orthopedics and sports medicine. 
Since cartilage injury is often combined with subchondral bone injury2, the ideal 
intervention should treat both cartilage and subchondral bone. Bone marrow stimulation 
technology is currently the most commonly used treatment method3, which has the 

advantages of low technical requirements, low cost, minimally invasive and mild 
postoperative pain, and many clinical studies have shown that it can achieve satisfactory 
short- and medium-term clinical efficacy, but the repaired tissue formed after surgery is 
fibrocartilage, and it is difficult to repair the lesions of the subchondral bone, and the 
medium- and long-term efficacy is not good4。 Autologous chondrocyte transplantation 
and autologous matrix- induced chondrogenesis can achieve good efficacy, but they 
require multiple surgeries, expensive surgery, high technical requirements, and cannot 
repair subchondral bone at the same time, and there is still insufficient evidence that such 
techniques can significantly improve the prognosis5. Although autologous or allogeneic 
osteochondral transplantation technology can repair cartilage and subchondral bone at 
the same time, autologous osteochondral transplantation can cause cartilage damage in 
the donor area, causing potential donor complications such as pain and arthritis6. 
Periosteo-bone grafting is grafted into the defect by embedding the periosteum and the 
derma/cancellous bone underlying it as a whole. Using the cartilage regeneration ability 
of periosteum to repair cartilage, healthy skin/cancellous bone can replace the 
subchondral plate and subchondral bone of the lesion, which can not only rebuild the 
biomechanical structure, but also provide natural attachment and nutritional support for 
the periosteum, improve the survival rate of the periosteum, and achieve integrated 
cartilage-subchondral bone repair. 
Periosteum-bone grafting can obtain the same clinical and imaging follow-up results as 
autologous osteochondral transplantation, and has the advantages of not needing to fix 
the periosteum, avoiding damage to healthy cartilage, low technical difficulty, low 
complication rate in the donor area, and wide range of sources, and has gradually 
replaced osteochondral transplantation in clinical practice8. 
However, at present, there are still the following problems in the repair of knee cartilage 
damage by periosteum-bone grafting: 1. Due to the morphological characteristics of the 
knee joint surface, the curvature of cartilage damage in different parts is inconsistent, and 
it is difficult for traditional periosteum-bone grafting technology to reconstruct the 
curvature of the knee joint surface and restore the flatness of the articular surface. Studies 
have shown that mismatch between the graft and the recipient area can lead to increased 
contact pressure, degeneration of surrounding healthy cartilage, and easy development 
of osteoarthritis9. 2. Because the form of injury varies from person to person, traditional 
periosteum-bone grafting techniques are difficult to dissect and reconstruct defects, and 
are prone to graft fracture. Studies have shown that reducing the gap between the graft 
and the bone-bone interface of the recipient area and maintaining the integrity of the 
graft are the keys to obtaining satisfactory long-term clinical efficacy10. 3. After cartilage 
injury, a large amount of inflammatory factors will be released in the joint fluid, and the 

infiltration and irritation of inflammatory factors are the main causes of pain, and the 
changes in the microenvironment in the joint will affect the healing ability of the 
subchondral bone and the regeneration ability of the periosteum11. 
Based on the above clinical problems, this project intends to carry out research from the 
following aspects: 1. Establish a segmentation model of cartilage and subchondral bone, 
accurately simulate the defect morphology, apply 3D printing technology to print bone 
guide plates, guide personalized material selection, and improve the matching degree of 
surface curvature and morphology between the graft and the recipient area; 2. The 
combined application of PRP and autologous periosteum-bone grafting is rich in a variety 
of growth factors and anti- inflammatory factors, and has the advantages of repairing 
cartilage damage and regulating inflammatory reactions12. 
References: 
（1） 
Curl WW，Krome J，Gordon ES，et al. Cartilage injuries: a review of 31， 516knee 
arthroscopies. Arthroscopy，1997，13（4）: 456-460 
（2） Bruns J, Werner M, Habermann C. Osteochondritis Dissecans: Etiology,Pathology, 
and Imaging with a Special Focus on the Knee Joint[J]. 
Cartilage, 2018,9(4): 346-362 
（3） 
Corr D, Raikin J, O'Neil J, et al. Long-term Outcomes of Microfracture for 
Treatment of Osteochondral Lesions of the Talus[J]. Foot Ankle Int, 2021: 
1071100721995427 
（4） 
Lee KB, Bai LB, Yoon TR, et al. Second-look arthroscopic findings and clinical 
outcomes after microfracture for osteochondral lesions of the talus[J]. Am J Sports Med, 
2009, 37 Suppl 1: 63s-70s 
（5） 
GaoL,Orth P, Cucchiarini M, et al. Autologous Matrix-Induced Chondrogenesis: 
A Systematic Review of the Clinical Evidence[J]. Am J Sports Med, 2019, 47(1): 222-231 
（6） 
Migliorini F, Maffulli N, Baroncini A, et al. Allograft Versus Autograft 
Osteochondral Transplant for Chondral Defects of the Talus: Systematic Review and 
Meta-analysis[J]. Am J Sports Med, 2021: 3635465211037349 
（7） 
Pereira GF, Steele JR, Fletcher AN, et al. Fresh Osteochondral Allograft 
Transplantation for Osteochondral Lesions of the Talus: A Systematic Review[J]. J Foot 
Ankle Surg, 2021, 60(3): 585-591 
（8） 
Shi W, Yang S, Xiong S, et al. Comparison of Autologous Osteoperiosteal and 
Osteochondral Transplantation for the Treatment of Large, Medial Cystic Osteochondral 

Lesions of the Talus[J]. Am J Sports Med, 2022: 3635465211068529 
（9） 
Kock LM, Ravetto A, van Donkelaar CC, et al. Tuning the differentiation of 
periosteumderived cartilage using biochemical and mechanical stimulations[J]. 
Osteoarthritis Cartilage, 2010, 18(11): 1528-1535 
（10） Shimozono Y, Yasui Y, Hurley ET, et al. Concentrated Bone Marrow Aspirate May 
Decrease Postoperative Cyst Occurrence Rate in Autologous Osteochondral 
Transplantation for Osteochondral Lesions of the Talus[J]. Arthroscopy, 2019, 35(1): 99- 
105 
（11） Gowd AK，Weimer AE，Rider DE，artilage restoration of bipolar lesions within 
the patellofemoral joint delays need for arthroplasty：A systematic review of rates of 
failure[J]．Arthrosc Sports Med Rehabil，2021，3(4)：e11 89 e1197 
（12）Belk JW，Kraeutler MJ，Houck DA．Platelet rich plasma versus hyaluronic acid for 
knee osteoar thritis：A systematic review and meta analysis of randomized controlled 
trials[J]．Am J Sports Med， 2021，49(1)：249 260 
Objectives of the study 
The purpose of the study was elaborated, including the study population, exposures, 
outcomes and methods. It can be expressed as specific hypotheses may be presented in 
the form of questions. 
Overall study design 
(1) A single-center prospective randomized controlled study of patients with knee 
cartilage injury using 3D printing-assisted PRP combined with autologous 
periosteum-bone grafting 
(2) Design type: prospective randomized controlled trial 
(3) Research subjects: Patients with unilateral knee cartilage injury area 
>2CM2 and grade 3-4 by the international cartilagerepair society (ICRS). 
(4) Interventions: 3D printing, PRP 
(5) Allocation ratio: 30 patients with 3D printing-assisted autologous periosteum-bone 
grafting, and 30 patients with 3D printing-assisted PRP combined with autologous 
periosteum-bone grafting research objectives to verify the safety and efficacy of 3D 
printing-assisted platelet-rich plasma combined with autologous osteoperiosteal 
transplantation in the treatment of knee cartilage injury. 

Research objectives 
Overall Objectives:  
The application of 3D printing to assist platelet-rich plasma combined with autologous 
osteoperiosteal transplantation in the treatment of knee cartilage injury can accurately 
restore surface curvature, anatomically reconstruct the defect morphology, improve the 
cartilage repair effect, and improve clinical efficacy and knee joint function. 
(1) Based on the deep learning method of knee cartilage and subchondral bone 
segmentation, a segmentation model of cartilage and subchondral bone is 
established, and the three-dimensional reconstruction of cartilage and subchondral 
bone is carried out through the method of body drawing and surface drawing, so as 
to visually display the cartilage defect at the knee junction from multiple angles, and 
3D print the bone extraction template to improve the graft matching degree. 
(2) The application of PRP combined with autologous periosteum-bone grafting 
technology to repair cartilage defects can improve the cartilage repair effect and 
improve clinical efficacy. 
Achieveable results and intellectual property information: 
(1) Establish a segmentation model of cartilage and subchondral bone, formulate a 3D 
printing bone retrieval module and personalized bone extraction process, and 
combine PRP and autologous periosteum-bone grafting technology to form an 
integrated anatomical-biological-functional repair technology for cartilage defects. 
(2) Publish 1-3 high-level SCI research papers, apply for 1-2 patents, and train 1-3 
graduate students 
Study design 
1. Research site and research population Research site 
Institution: Department of Orthopedics, The Second Affiliated Hospital of Nanchang 
University 
Time Frame: January 1, 2025 to December 31, 2027 (case inclusion and intervention 
period) 
Selection of research objects Implementation of norms Source: Orthopedic 
outpatient/inpatient department, patients with unilateral knee cartilage injury confirmed 
by MRI 
Inclusion criteria: (1) Age 18-65 years; ②BMI 18-30 kg/m²； (3) Cartilage damage 
area >2cm² and ICRS grade 3-4; (4) The lower limb force line is normal:  

Exclusion Criteria: (1) Osteoporosis; (2) Immature bones; (3) combined meniscus/ligament 
injury; (4) Knee joint effusion; (5) History of immunosuppressant use 
Sampling method: Continuous enrollment (non-probability sampling) until sample size is 
reached 
Grouping method: block randomization (block size 4), stratified by ICRS grading (3/4 
grade).Follow-up strategy: Outpatient follow-up at 1/3/6/12 months after surgery, and 
telephone follow-up visits (≤ 2 times) for those who lost follow-up 
2. Sample size calculation 
Sampling method: Continuous enrollment (non-probability sampling) until sample size is 
reached 
Grouping method: block randomization (block size 4), stratified by ICRS grading (3/4 
grade). 
Follow-up strategy: Outpatient follow-up at 1/3/6/12 months after surgery, and 
telephone follow-up visits (≤ 2 times) for those who lost follow-up 
2. Sample size calculation 
Primary endpoint: MOCART score (continuous variable) at 12 months postoperatively 
Parameter setting (based on previous literature and pre-experiments): 
Expected mean value of PRP group: 85 points The expected mean of the control group: 
70 points 
Pooled standard deviation (SD): 12 points α=0.05 (bilateral), β=0.20 (80% grasp) 
Between-group difference: 15 points (clinically significant difference) Formula and 
calculation 
 
Adjust with final sample size 
 
Consider a 20% dropout rate: $n_{adjusted} = 21 / (1-0.2) = 26.25 \rightarrow 27 
example/group $ 
, g statistical mation) 
Actual in clusion: 30 cases/group (60 cases in total), meetin requirements and reserving 
redundancy. 

Calcu lation tool: PASS 2021 software (verification confir mation). 
3. Bias control measures Design phase. 
Types of bias 
Control measures 
Selection bias 
- Strictly follow inclusion/exclusion criteria 
- Hierarchical randomization (balancing 
ICRS grading impact) 
Information bias 
-Double-blind 
imaging 
evaluation: 
orthopedic and radiologist independent 
reading (not knowing grouping) 
-Standardized 
scale 
training 
(Lysholm/Tegner) 
Confounding bias 
- 
Multivariate 
analysis 
adjusts 
for 
covariates such as age, BMI, and damage 
area 
Implementation phase 
Surgical standardization: All surgeries are performed by the same senior doctor (annual 
operation volume >600 units). 
PRP preparation quality control: fixed centrifugation parameters (1500g × 10min), 
operated by special personnel. 
Data collection: Electronic CRF real-time verification (e.g., postoperative score should not 
be better than preoperative). 
Analysis phase:  
Sensitivity analysis: 
1. They were analyzed separately by PPS vs FAS  
2. Nonparametric test for MOCART score (Wilcoxon rank sum) 
Subgroup analysis: The interaction effect between the group and the injury area (≤4cm
² vs >4cm²) was tested technology-related bias control 
Verification of 3D printing accuracy: The matching error between preoperative simulation 
and postoperative MRI was controlled at <0.5mm 
Deep learning model: ablation experiment verifies the stability of segmentation algorithm 
(DSC>0.85). 
Safety evaluation (including definition and evaluation of adverse events and serious 
adverse events, etc.) 
Within 12 months after surgery, the MOCART score was performed by MRI imaging to 

observe the safety of this product. Evaluate the stability of the implant and whether the 
implant is loose, dislocated, deformed, or fractured.  
Adverse events should be closely observed and evaluated in the trial, and clinical adverse 
reactions should be followed up until symptoms disappear, and strictly recorded in the 
original case table and case report form. 
3D printing technology can simulate the morphology and curvature of the lesion area, 
which has been widely used in the field of orthopedics, and the role of PRP and 
periosteum-grafting in the repair of talar cartilage damage has been clinically and 
imaging, respectively, and is a safe treatment. Therefore, the risk assessment is the 
minimum risk. 
Side effects and adverse events 
1. 
Infection: including skin infection and deep wound infection, antibacterial drugs 
should be used before and after surgery. 
2. 
Venous thrombosis and pulmonary embolism: When it comes to lower limb surgery, 
lower limb thrombosis is more common, and most of them can be cured; 
Elevate the affected limb, use hemostatic drugs with caution and control the time of 
medication. 
3. 
Neurovascular injury: In cases with unclear anatomical structure or serious 
neurovascular involvement, try to pay attention to the operation during the 
operation. 
4. 
Heart, lung and brain complications are rare, but in severe cases they can be life-
threatening. 
5. 
Fractures: Intraoperative fractures are more common in elderly patients with severe 
osteoporosis, and postoperative fractures are mostly caused by patients 
not fully following the doctor's instructions for functional rehabilitation. 
6. 
Loosening or infection around the graft continues to occur after surgery 
7. 
Poor activity. 
Reasons for serious adverse events: 
1. Causing death; 2. Threatening life; 3. Causing hospitalization or prolongation of 
hospitalization; 4. Causing continuous or significant loss of function of the human 
body. The probability of complications is related to the patient's physical condition, the 

difficulty of surgery and other factors, but most of these complications can be cured. 
Before surgery, the doctor should evaluate the patient's physical condition, estimate the 
risk of surgery and the probability of complications, and make corresponding treatment 
and prevention. 
 
Data collection and management 
1.Survey content (CRF form) 
Measurement and collection of indicators including exposure and outcomes. Clearly 
define variables such as outcomes, exposure, predictors, potential confounders, and 
effect modifiers. 
Variable type 
Specific indicators 
Measurement 
Methods/Tools 
Outcome indicators 
 
Primary endpoint 
MOCART score at 12 
months postoperatively 
MRI imaging evaluation 
(double-blind reading) 
Secondary endpoints 
Lysholm score, Tegner 
motor score, pain NRS 
score (preoperatively, 
1/3/6/12 months 
postoperatively) 
Standardized scale 
(outpatient/tele phone 
follow- up) 
Exposure variables 
 
 
Intervention grouping 
PRP+periosteum-bone 
graft group vs 
periosteum-bone graft 
group 
Randomly assign records 
PRP preparation 
parameters 
Centrifugal force (1500g), 
centrifugation time 
(10min), blood collection 
volume (18ml) 
Laboratory operation 
records 
3D printing matching 
Graft chimerism, surface 
curvature matching (MRI 
mirror assessment on 
postoperative day 2) 
Quantitative analysis of 3D 
reconstruction software 
Confounding factors 
 
 
Demographic 
characteristics 
Age, gender, BMI, trauma 
history 
Baseline questionnaire 
Disease characteristics 
Cartilage injury area (cm²), 
ICRS grade (grade 3/4), 
injury site 
Preoperative MRI 
evaluation 
Concomitant lesions 
History of meniscus injury, 
ligament injury (exclusion 
Preoperative arthroscopic 
recordings 

criteria) 
Effect modifiers 
BMI stratification (<24 vs 
≥24) and damage area 
stratification (2-4cm² 
vs >4cm²). 
Subgroup analysis variables 
2.Data 
management 
and 
statistical 
analysis 
(data 
management: 
including 
paper/spreadsheet, database creation and entry, whether to double enter, whether to 
collect electronic data; Database cleaning and locking, data archiving, etc. Statistical 
analysis: statistical description, inter-group comparison, multivariate analysis and other 
methods, confounding factor control methods, subgroup analysis and interaction effect 
analysis, missing value treatment methods, sensitivity analysis, etc. ） 
 
Data management process 
tache 
mplement the norms 
Data acquisition 
- 
Paper CRF → Two-person independent entry
 
into electronic database (EpiData or REDCap) -
 
Image data: DICOM files are encrypted and 
stored to match subject IDs 
quality control 
- 
Logical verification rules (e.g., postoperative 
scoring> preoperative scoring trigger verification) 
- 
Randomly select 10% of CRFs for source data 
verification (SDV) 
Database lock 
Lock after blind audit 
Changes must be signed and approved by the 
PI 
Data archiving 
The original CRF is kept for 15 years, and the electronic 
database is backed up to the hospital's encrypted server 
Statistical analysis plan 
1. 
Statistical description 
-Continuous variables: 'Mean± standard deviation' (normal) or 'Median (P25, P75)' (non-
normal). 
- Categorical variables: frequency (percentage). 
- Comparison of baseline equilibrium between the two groups: t- test/Mann-Whitney U 
test (continuous variable); Chi-square test (categorical variable). 
2. 
Primary outcome analysis 
-**Primary endpoint (MOCART score)**: Analysis of covariance (ANCOVA), with baseline 
score as covariate and group as fixed factor 
-**Secondary endpoint (functional score)**: Repeated measures analysis of variance 
(group × time interaction effects). 

-If the spherical test P<0.05, use the Greenhouse-Geisser correction 
-Comparison between groups: Bonferroni correction 
3. 
Consuming control and sensitivity analysis 
-**Multivariate model**: Establish multiple linear regression for the primary endpoint, 
adjusting for age, BMI, and damage area 
-**Subgroup analysis**: Stratified by BMI/injury area, to test the interaction effect of 
stratification factors × groups 
-**Sensitivity Analysis**:: Protocol set (PPS) vs full analysis set (FAS). 
Nonparametric tests (e.g., Wilcoxon rank-sum test for MOCART scores). 
4. 
Missing data processing 
-≤5% missing: Delete missing cases directly 
->5% missing: multiple imputation (continuous variables: predicted mean matching; 
Categorical variables: Logistic regression imputation). 
5. 
Additional analysis 
-Correlation of graft match with MOCART score (Pearson/Spearman correlation). 
-Dose-effect relationship within PRP group (PRP volume vs functional score 
improvement). 
Principles of statistical analysis 
The statistical analysis of the main and secondary efficacy indicators and safety indicators 
of the trial will be performed according to the protocol dataset, that is, all the subject 
data that meet the requirements of the trial protocol will be statistically analyzed, and the 
mean ±  standard deviation will be used for the mean data. The frequency (or 
composition ratio) of the counting data is used. Two- sided test t-test and equivalence 
test were used for continuous data, χ2 test (or exact Fisher test) was used for count data, 
and Mann-Whitney rank test was used for rank data. 
Primary and secondary efficacy indicators (measurement data) were adopted 
(1) Statistical description; 
(2) Analysis of variance; 
Safety indicators (count data), adopted 
(1) Statistical description; 

(2) Analysis of variance; 
Quality management plan (please introduce the relevant measures to ensure the quality 
and progress of the project) 
Feasibility analysis 
(1) The applicant has been engaged in clinical and basic research on joint diseases for a 
long time, and the first completer has won the first prize of Jiangxi Provincial Science and 
Technology Progress Award and Jiangxi Medical Youth Science and Technology 
Innovation Award, presided over and completed a national youth fund, a national 
regional fund, and a key research and development project related to cartilage repair, 
with solid research experience, and completed more than 600 joint surgeries every year, 
with rich surgical experience, and team members have rich clinical research experience, 
which can ensure postoperative investigation and follow-up. It can ensure the smooth 
progress of this study; 
(2) The applicant's unit has a sufficient number of patients with cartilage damage and 
has various equipment to implement the study; 
(3) This group has accumulated a good preliminary work foundation in PRP, cartilage 
segmentation, 3D printing and autologous periosteal-bone graft surgery (see the basic 
part of the research). Based on the above reasons, this project has good feasibility. 
Research Basis 
(1) The project team proposed a parallel expansion U-Net (dila-UNet) to extract deep 
features, achieve more accurate bits, generate adversarial network (GAN) connection 
mechanism and contrast learning module, compared with the current state-of-the-art 
deep learning algorithm, the accuracy of segmentation area is increased by 3.8%, the 
judgment anomaly rate is reduced by 1.82%, and finer edge recognition is achieved. MFA-
Net:Multiple Feature Association Network for medical image segmentation. [J]. Comput 
Biol Med,2023,:106834。 The conditions of 3D printing have been explored, and the 
preliminary exploration of assisted personalized bone retrieval has been carried out 
(2) Rich experience in developing new technologies, which have been commended by 
the hospital as "advanced in China" and "advanced in the province". Periosteum-bone 
graft repair cartilage damage has been declared a new technology in the hospital, and 
the acquisition tool of periosteum-bone graft has been improved, and a patent is being 
applied. The application of this technology has carried out corresponding cases and 
obtained good follow-up results 
Pre-assessment and risk control plan of project risk benefits 

Please describe the risks and benefits that may be borne by the researcher, subjects, and 
medical institutions when carrying out this project; If there is a risk, please introduce the 
measures and feasibility of risk control. 
Benefit/risk assessment  
Expected benefits 
(1) Patient benefits: 3D printing-assisted PRP combined with autologous periosteum-
bone grafting repairs knee cartilage damage, relieves pain, improves knee joint mobility, 
delays the occurrence of osteoarthritis, and improves knee joint function. (2) Social 
benefits: Through the research of this project, a more accurate and effective method will 
be provided for the repair of knee cartilage damage, promoting the development of 
cartilage repair technology, and conducive to the improvement of the treatment level of 
joint diseases. 
Risk assessment 
3D printing technology can simulate the morphology and curvature of the lesion area, 
which has been widely used in the field of orthopedics, and the role of PRP and 
periosteum-grafting in the repair of talar cartilage damage has been clinically and 
imaging, respectively, and is a safe treatment. Therefore, the risk assessment is the 
minimum risk 
Morality and ethics 
Ethics Committee (should describe how the plan was approved by the Research Ethics 
Committee/Institutional Review Committee) 
(1) Research plan: The purpose, methods, participant recruitment process, risk 
assessment and control measures of this study have been explained in detail in the 
application form. 
(2) Informed consent form (ICF): There is a clear informed consent form, which clarifies 
the various rights and rights of participants (voluntary withdrawal, 
privacy protection, data use). 
(3) Data management plan: It has a complete data collection, storage (such as 
anonymization), sharing and destruction party 
(4) Participant recruitment materials: recruited through the hospital platform. 
(5) Researcher qualification certificate: Team members have ethics training certificates. 
(6) Conflict of interest statement: There is no potential interest relationship with the 

partner. 
Patient information and informed consent 
(1) Who will obtain informed consent The investigator should usually be responsible for 
obtaining the subject's informed consent. The patient instructions may also be explained 
to the subject by a qualified study coordinator, and informed consent will be obtained by 
the investigator and confirmed that the subject is aware of all information related to the 
trial15. Application for in- hospital funding projects of the Second Affiliated Hospital of 
Nanchang University 
(2) How to obtain informed consent After the subject is fully informed of the study 
information by a qualified person, the subject or his/her legal representative shall sign 
and date the informed consent form, and the researcher who performs the informed 
consent process shall also sign the name and date on the informed consent form. 
(3) Compensation clause for harm caused by participation in the trial The sponsor shall 
take appropriate measures to ensure that the subject and the investigator can be 
compensated or compensated: First, the sponsor shall bear the diagnosis and treatment 
costs of the subject related to the damage or death of the clinical trial, as well as the 
corresponding compensation. The sponsor and the investigator shall promptly pay the 
compensation or compensation given to the subject. Second, the methods and methods 
provided by the sponsor to the subjects shall comply with relevant laws and regulations. 
Third, the sponsor shall provide the experimental drug to the subjects free of charge and 
pay for the medical testing costs related to the clinical trial 
Relevant information on human genetic resources 
Human genetic resources materials refer to organs, tissues, cells and other genetic 
materials containing human genomes, genes and other genetic materials. 
Human genetic resources information refers to data and other information materials 
generated by human genetic resources materials. 
Not involved