clinical trial protocol
untitled h2

Patient-Customized Bioprinting Technology for Practical Regeneration of the Respiratory Tract (Trachea)  
| Protocol No.     | :   | 3D Bioprinting Trachea   |
|------------------|-----|--------------------------|
| Protocol Version | :   | 2.3                      |
| Development date | :   | 2023-05-26               |  
| CLINICAL TRIAL PROTOCOL: CLINICAL RESEARCH PLAN OVERVIEW Professor Bae Ja-sung, Seoul St. Mary's Hospital Patient-Customized Bioprinting Technology for Practical  Regeneration of the Respiratory Tract (Trachea) Study Title Patient-Customized Bioprinting Technology for   | Practical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               |                   |      |         |       |     |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------|------|---------|-------|-----|
| Regeneration of the Respiratory Tract (Trachea)                                                                                                                                                                                                                                |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         |                   |      |         |       |     |
| Principal                                                                                                                                                                                                                                                                      | Professor Bae Ja-sung, Catholic University of Korea, Seoul St. Mary's Hospital                                                                                                                                                                                                                                                                                                                                                                                                                                                          |                   |      |         |       |     |
| Investigator  Clinical Research                                                                                                                                                                                                                                                | Catholic University of Korea, Seoul St. Mary's Hospital                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 |                   |      |         |       |     |
| Institution Reference                                                                                                                                                                                                                                                          | Bae Ja-sung, et al. Rational Tissue Engineering Strategy for Extensive  Circumferential Tracheal Reconstruction Using Three-Dimensional (3D)  Printing. Biomaterials. 2018;185:276-283.                                                                                                                                                                                                                                                                                                                                                 |                   |      |         |       |     |
| Period                                                                                                                                                                                                                                                                         | 72 months from IRB approval                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             | Stage             | Cell | therapy | phase | for |
| date                                                                                                                                                                                                                                                                           | academic purposes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       |                   |      |         |       |     |
| Objective                                                                                                                                                                                                                                                                      | This clinical study aims to assess the effectiveness and safety of transplanting  3D patient-specific bioprinted tracheal organs using biopolymers, hydrogels,  and tissue regeneration cells for respiratory tract regeneration.                                                                                                                                                                                                                                                                                                       |                   |      |         |       |     |
| Methods                                                                                                                                                                                                                                                                        | Participants with thyroid or airway diseases necessitating partial or segmental  resection will be enrolled after providing written consent. Screening tests will  determine eligibility. The 3D bioprinted trachea, incorporating stem cells from  the nasal cavity and nasal septum cartilage, will be transplanted. Evaluation  includes endoscopy, bronchoscopy, CT, and lab tests. Neck fixing splints will  stabilize transplanted areas post-surgery. Thyroid cancer patients will have  extended follow-up with specific tests. |                   |      |         |       |     |
| Number                                                                                                                                                                                                                                                                         | of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      | 1                 |      |         |       |     |
| Participants Target Disease                                                                                                                                                                                                                                                    | Congenital tracheal softening, traumatic tracheal stenosis, tracheal defects                                                                                                                                                                                                                                                                                                                                                                                                                                                            |                   |      |         |       |     |
| post-thyroid cancer surgery, requiring partial or segmental resection                                                                                                                                                                                                          |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         |                   |      |         |       |     |
| Selection/Exclusio                                                                                                                                                                                                                                                             | Selection Criteria:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     |                   |      |         |       |     |
| n Criteria                                                                                                                                                                                                                                                                     |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | Adults aged 19-75 |      |         |       |     |
|                                                                                                                                                                                                                                                                               | Patients meeting criteria for thyroid or airway disease requiring resection                                                                                                                                                                                                                                                                                                                                                                                                                                                             |                   |      |         |       |     |
|                                                                                                                                                                                                                                                                               | Patients with thyroid cancer invading the trachea, requiring resection with  expected organ dysfunction post-surgery                                                                                                                                                                                                                                                                                                                                                                                                                    |                   |      |         |       |     |
|                                                                                                                                                                                                                                                                               | Patients with organ defects around cartilage (>30%), suitable for 3D  bioprinting                                                                                                                                                                                                                                                                                                                                                                                                                                                       |                   |      |         |       |     |
|                                                                                                                                                                                                                                                                               | Female participants using contraception during the study                                                                                                                                                                                                                                                                                                                                                                                                                                                                                |                   |      |         |       |     |
|                                                                                                                                                                                                                                                                               | Participants providing informed consent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 |                   |      |         |       |     |  
| Exclusion Criteria:   Pregnant or lactating women   Prior thyroid or airway peripheral surgery   Inflammation of thyroid or surrounding tissues   Systemic inflammatory disease   High risk due to liver, kidney, or heart disease   Sepsis or hemorrhagic predisposition   Prior radiotherapy to head/neck   Recent use of other research medications/devices   History of cell therapy   Malignant tumors other than thyroid cancer   Other deemed inappropriate for the study   |                                                                                                   |                                                 |
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| Product                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       | 3D cell-printed trachea using patient-specific cells (hNTSCs, hNCs) and                           |                                                 |
| Description                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   | hydrogels  Patient-specific single-product bioprinted trachea  No artificial genetic manipulation |                                                 |
| Validity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      | Primary Variables:                                                                                |                                                 |
| Assessment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    |                                                                                                  | Endoscopic findings after 1, 2, 4, and 24 weeks |
|                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | Airway intraluminal clearance rate                                                                |                                                 |
|                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | Degree of granuloma and bark formation                                                            |                                                 |
|                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | Inflammation and other findings                                                                   |                                                 |
| Secondary outcome   CT-based airway condition comparison   Postoperative inflammatory levels (WBC, WBC Diff, CRP, ESR)   Bronchoscopy findings (wall stability, tracheal opening, mucosal formation,  inflammation/granulation)                                                                                                                                                                                                                                                            |                                                                                                   |                                                 |
| Safety                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | Abnormal responses, vital signs, ECG, lab tests, physical exam                                    |                                                 |
| Assessment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    |                                                                                                   |                                                 |