Patient-Customized Bioprinting Technology for Practical Regeneration of the Respiratory Tract (Trachea)
Study Details
Study Description
Brief Summary
This clinical trial aims to assess the effectiveness and safety of a novel approach utilizing biopolymers, hydrogels, mucous membranes, and cartilage tissue regeneration cells integrated into 3D bioprinting technology for the creation and implantation of patient-specific tracheal organs.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Study Objective:
This clinical study focuses on patients with thyroid or airway diseases necessitating partial or segmental organ resection. The objective is to evaluate the feasibility, efficacy, and safety of transplanting functional patient-specific bioprinted tracheal organs as an innovative regenerative approach.
Patient Enrollment:
Patients voluntarily participate and provide written consent. A thorough screening procedure is conducted to determine their eligibility based on selection and exclusion criteria.
Bioprinting Process:
The study employs cutting-edge bioprinting technology to create complex organ tissues. Specifically, 3D cell printing is employed to fabricate a bioprinted tracheal organ. Stem cells derived from the human nasal cavity and nasal septum cartilage cells are integrated to form a cell-supporting body.
Transplantation Procedure:
Eligible patients receive transplantation of the functional patient-specific bioprinted trachea. The transplantation aims to restore tracheal functionality and address the unique challenges posed by thyroid and airway diseases.
Evaluation and Monitoring:
Following transplantation, a comprehensive assessment regimen is undertaken to evaluate both the effectiveness and safety of the procedure. This includes flexural laryngeal endoscopy, bronchoscopy, computed tomography (CT) scans, and laboratory tests.
Post-Transplant Measures:
To ensure the stability of the transplanted organ immediately after the procedure, neck fixing splints are employed to limit movement.
Thyroid Cancer Patients:
For patients diagnosed with thyroid cancer, a distinct follow-up protocol is established. A five-year observation period is implemented, extending beyond the standard follow-up for general cancer patients. Additional observations include thyroid ultrasound, Free T4, Thyroid-Stimulating Hormone (TSH), Thyroglobulin Antigen (Thyroglobulin Ag), and Anti-Thyroglobulin Antibody (Anti-TG Ab) tests conducted at the designated observation points.
This study seeks to contribute novel insights into the realm of regenerative medicine and enhance the understanding of patient-specific bioprinting technology as a potential solution for tracheal and airway diseases.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treated Three-dimensional patient-specific bioprinting trachea implantation |
Procedure: Three-dimensional patient-specific bioprinting trachea implantation
The intervention entails the creation of a 3D cell-printed tracheal organ, achieved through the fusion of biopolymer materials and the bioprinting (3D cell printing) technique. This process involves distribution of nasal cavity stem cells (hNTSCs) and nasal septum cartilage cells (hNCs) within hydrogel matrices, culminating in the formation of a personalized tracheal structure.
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Outcome Measures
Primary Outcome Measures
- airway lumen opening rate [1 week, 2 weeks, 4 weeks, 24 weeks, 2 years]
measured by curved laryngeal endoscopy
- crust formation degree [1 week, 2 weeks, 4 weeks, 24 weeks, 2 years]
measured by curved laryngeal endoscopy
- granuloma formation degree [1 week, 2 weeks, 4 weeks, 24 weeks, 2 years]
measured by curved laryngeal endoscopy
- degree of inflammation [1 week, 2 weeks, 4 weeks, 24 weeks, 2 years]
measured by curved laryngeal endoscopy
- other relevant findings [1 week, 2 weeks, 4 weeks, 24 weeks, 2 years]
measured by curved laryngeal endoscopy
Secondary Outcome Measures
- Airway State on CT [4 weeks]
airway patency by ratio compared to preoperative state
- white blood cell count (WBC) [4 weeks, 48 weeks, 2years]
Serum inflammatory markers
- differential white blood cell count (WBC Diff) [4 weeks, 48 weeks, 2years]
Serum inflammatory markers
- C-reactive protein (CRP) [4 weeks, 48 weeks, 2years]
Serum inflammatory markers
- erythrocyte sedimentation rate (ESR) [4 weeks, 48 weeks, 2years]
Serum inflammatory markers
- stability of bronchial wall structure [4 weeks, 48 weeks, 2years]
measured by bronchoscopy
- degree of organ opening [4 weeks, 48 weeks, 2years]
measured by bronchoscopy
- mucous membrane formation [4 weeks, 48 weeks, 2years]
measured by bronchoscopy
- presence of inflammatory or healing tissue [4 weeks, 48 weeks, 2years]
measured by bronchoscopy
Other Outcome Measures
- Incidence of Treatment-Emergent Adverse Events [1 week, 2 weeks, 4 weeks, 24 weeks, 48 weeks, 72 weeks, 2 years]
Safety and Tolerability
Eligibility Criteria
Criteria
Inclusion Criteria:
- Age Range:
Individuals between 19 and 75 years of age are eligible for participation.
- Specific Medical Condition:
Patients must meet the following criteria and have thyroid or airway diseases necessitating partial or segmental resection:
- Thyroid Cancer Patients:
For patients with thyroid cancer, inclusion is based on TNM staging, specifically stage II or higher differentiated thyroid cancer patients. Verification of complete removal through a freeze section test during surgery in accordance with the staging system for papillary carcinoma of the trachea is essential (Hum Pathol. 1993 Aug; 24(8):866-70).
Patients for whom conventional reconstruction methods, including single-stage anastomosis, are infeasible and require alternative approaches like flap reconstruction.
Patients suitable for single anastomosis, but assessed to derive more benefits than risks from 3D bioprinting, considering factors such as post-surgery aftereffects, complications, prolonged recovery, and potential decline in quality of life due to surgical intervention.
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Defect Size Patients with defects encompassing more than 30% of the cartilage around the affected organ are eligible. Smaller defects may also qualify if reinforcing defects using soft tissue is infeasible due to factors such as surrounding inflammation, tissue instability, tissue adhesion, unstable blood supply, or the anticipation of reoperation during reconstruction.
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Pregnancy Consideration:
In the case of childbearing women, individuals must provide a negative result on a pregnancy test and commit to using contraception throughout the clinical study period.
- Informed Consent:
Participants must voluntarily provide written consent after receiving a comprehensive explanation of the clinical study.
Exclusion Criteria:
- Pregnancy and Lactation:
Pregnant or lactating women are excluded from participation in the study.
- Prior Thyroid or Airway Surgery:
Individuals who have undergone thyroid or airway peripheral surgery before undergoing screening are ineligible for participation.
- Persistent Inflammation:
Patients with ongoing inflammation of the thyroid or surrounding tissues at the time of screening are excluded.
- Systemic Inflammatory Disease:
Patients diagnosed with systemic inflammatory diseases at the screening stage are not eligible to participate.
- Anesthesia Risk Factors:
Individuals with a high risk of complications associated with general anesthesia due to existing liver disease, kidney disease, or heart disease are excluded.
- Sepsis:
Patients diagnosed with sepsis at the time of screening are not eligible for participation.
- Hemorrhage Predisposition:
Individuals with a predisposition to hemorrhage at the time of screening are excluded from the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Seoul St. Mary's Hospital | Seoul | Korea, Republic of | 06591 |
Sponsors and Collaborators
- Ja Seong Bae, MD, phD
- Korea Health Industry Development Institute
Investigators
- Study Chair: Sung Won Kim, MD, PhD, Seoul St. Mary's Hospital
Study Documents (Full-Text)
More Information
Publications
None provided.- CMCENT-02