Patient-Customized Bioprinting Technology for Practical Regeneration of the Respiratory Tract (Trachea)

Development of the Practical Usage Based Technology Using the Patient Customized Bioprinting Trachea for the Regeneration of Respiratory Tract (Trachea)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Thyroid Cancer
• Intervention / Treatment: Procedure: Three-dimensional patient-specific bioprinting trachea implantation

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06591
    • Seoul St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age Range:

   Individuals between 19 and 75 years of age are eligible for participation.

2. Specific Medical Condition:

   Patients must meet the following criteria and have thyroid or airway diseases necessitating partial or segmental resection:

   1. 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.

   2. 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.

3. 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.

4. Informed Consent:

Participants must voluntarily provide written consent after receiving a comprehensive explanation of the clinical study.

Exclusion Criteria:

1. Pregnancy and Lactation:

   Pregnant or lactating women are excluded from participation in the study.

2. Prior Thyroid or Airway Surgery:

   Individuals who have undergone thyroid or airway peripheral surgery before undergoing screening are ineligible for participation.

3. Persistent Inflammation:

   Patients with ongoing inflammation of the thyroid or surrounding tissues at the time of screening are excluded.

4. Systemic Inflammatory Disease:

   Patients diagnosed with systemic inflammatory diseases at the screening stage are not eligible to participate.

5. 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.

6. Sepsis:

   Patients diagnosed with sepsis at the time of screening are not eligible for participation.

7. Hemorrhage Predisposition:

Individuals with a predisposition to hemorrhage at the time of screening are excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
airway lumen opening rate	measured by curved laryngeal endoscopy	1 week, 2 weeks, 4 weeks, 24 weeks, 2 years
crust formation degree	measured by curved laryngeal endoscopy	1 week, 2 weeks, 4 weeks, 24 weeks, 2 years
granuloma formation degree	measured by curved laryngeal endoscopy	1 week, 2 weeks, 4 weeks, 24 weeks, 2 years
degree of inflammation	measured by curved laryngeal endoscopy	1 week, 2 weeks, 4 weeks, 24 weeks, 2 years
other relevant findings	measured by curved laryngeal endoscopy	1 week, 2 weeks, 4 weeks, 24 weeks, 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway State on CT	airway patency by ratio compared to preoperative state	4 weeks
white blood cell count (WBC)	Serum inflammatory markers	4 weeks, 48 weeks, 2years
differential white blood cell count (WBC Diff)	Serum inflammatory markers	4 weeks, 48 weeks, 2years
C-reactive protein (CRP)	Serum inflammatory markers	4 weeks, 48 weeks, 2years
erythrocyte sedimentation rate (ESR)	Serum inflammatory markers	4 weeks, 48 weeks, 2years
stability of bronchial wall structure	measured by bronchoscopy	4 weeks, 48 weeks, 2years
degree of organ opening	measured by bronchoscopy	4 weeks, 48 weeks, 2years
mucous membrane formation	measured by bronchoscopy	4 weeks, 48 weeks, 2years
presence of inflammatory or healing tissue	measured by bronchoscopy	4 weeks, 48 weeks, 2years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Safety and Tolerability	1 week, 2 weeks, 4 weeks, 24 weeks, 48 weeks, 72 weeks, 2 years

Collaborators and Investigators

• Sponsor: Ja Seong Bae, MD, phD
• Collaborators: Korea Health Industry Development Institute
• Investigators: Study Chair: Sung Won Kim, MD, PhD, Seoul St. Mary's Hospital

Publications and helpful links

General Publications

• Park JH, Hong JM, Ju YM, Jung JW, Kang HW, Lee SJ, Yoo JJ, Kim SW, Kim SH, Cho DW. A novel tissue-engineered trachea with a mechanical behavior similar to native trachea. Biomaterials. 2015 Sep;62:106-15. doi: 10.1016/j.biomaterials.2015.05.008. Epub 2015 May 23.
• Park JH, Park JY, Nam IC, Ahn M, Lee JY, Choi SH, Kim SW, Cho DW. A rational tissue engineering strategy based on three-dimensional (3D) printing for extensive circumferential tracheal reconstruction. Biomaterials. 2018 Dec;185:276-283. doi: 10.1016/j.biomaterials.2018.09.031. Epub 2018 Sep 19.
• Park JH, Park JY, Nam IC, Hwang SH, Kim CS, Jung JW, Jang J, Lee H, Choi Y, Park SH, Kim SW, Cho DW. Human turbinate mesenchymal stromal cell sheets with bellows graft for rapid tracheal epithelial regeneration. Acta Biomater. 2015 Oct;25:56-64. doi: 10.1016/j.actbio.2015.07.014. Epub 2015 Jul 9.

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2023
• Primary Completion (Actual): August 16, 2023
• Study Completion (Estimated): August 16, 2025

Study Registration Dates

• First Submitted: August 29, 2023
• First Submitted That Met QC Criteria: September 20, 2023
• First Posted (Actual): September 25, 2023

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Trachea
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Tracheal Diseases
• Other Study ID Numbers: CMCENT-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No