3D BIO-STRUCTURES FOR G.I. POST-SURGICAL DEFECTS (3DReG)

3D BIO-STRUCTURES POPULATED WITH MICRO-FRAGMENTED, EMULSIFIED STROMAL TISSUE DERIVED FROM AUTOLOGOUS ADIPOSE TISSUE HARVESTING FOR THE REGENERATIVE TREATMENT OF POST-SURGICAL DEFECTS OF THE GASTROINTESTINAL TRACT

The study is focused on evaluating the safety and efficacy of using vascular stromal tissue, derived from autologous adipose tissue, and subjected to microfragmentation and emulsification (Stromal Vascular Fraction Micro-Emulsion - tSVFem), in the treatment of chronic gastrointestinal fistulae (CGF). Tissue regeneration will be stimulated using 3D bio-printed scaffolds, enriched at implantation with mesenchymal stem cells derived from patients' adipose tissue; injection of tSVFem and scaffold placement will be performed endoscopically. The study proposes to use 3D bioprinting to create customized polymeric bioinks (gels) on supporting scaffolds that can serve as a framework for the growth and development of the patient's cells. This approach aims to promote tissue regeneration and integration, repair extensive CGF and restore the proper microbiota.

A small portion of the patient's tSVFem will be injected in a bioreactor into the scaffolds and used for evaluation of the ability of the scaffolds to support cell proliferation, migration, and differentiation, as well as secretion of cytokines and growth factors and the immunological response. Also, to analyze the effect on cells and microbial species, the intestinal microbiota will be analyzed in a bioreactor under different dynamic conditions on the growth and differentiation of the MSCs contained in tsVFem, on the bio-printed scaffolds and the immunological results.

Study Overview

• Status: Not yet recruiting
• Conditions: Fistula
• Intervention / Treatment: Device: Endoscopic procedure

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    • Contact: Massimiliano Papi; Phone Number: +39 06 3015 4566; Email: massimiliano.papi@unicatt.it

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• patients with CGF at any level that can be approached endoscopically and for whom the possibility of conventional conservative treatment is ruled out, or all possible conservative or surgical treatments have already been performed without benefit, or in whom the reiteration of such treatments is contraindicated, because of life-threatening, and/or possible complications, and/or disabling outcomes.

Exclusion Criteria:

• patients who have not given informed consent to the procedure;
• patients with entero-enteral CGF,
• patients who have therapeutic options of other type.

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: Endoscopic procedure	Device: Endoscopic procedure; tSVFem injection + 3D scaffold placement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of the custom-made 3D printed vascular stromal tissue and scaffolds to treat CGFs.	Efficacy: endoscopic evaluation with or without radiological auxilium at 3 months after the procedure. Fistula will be described as: closed or still open. Further endoscopic evaluations with or without radiological auxilium could be repeated to assess maintenance of the closure.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of immunological response	Exposure of the tSVFem-containing scaffolds to peripheral blood mononuclear cells obtained from the same patient. Microbiota analysis (obtained from stool sample of the patient) before and after the treatment. DNA extraction, metagenomics or 16S rRNA gene sequencing will be used to determine the diversity and abundance of the microbial community. Statistical analysis will be performed to identify specific microbial taxa that have changed significantly. PICRUSt2 and ALDEx2 tools will be applied to identify microbial signatures	24 months
Incidence of Treatment-Emergent Adverse Events	treatment-related adverse events as assessed by CTCAE v5.0 will be registered during follow-up	24 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Collaborators: IRCCS Ospedale Casa Sollievo della Sofferenza

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): June 10, 2026
• Study Completion (Estimated): September 10, 2026

Study Registration Dates

• First Submitted: August 28, 2024
• First Submitted That Met QC Criteria: September 4, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Fistula
• Other Study ID Numbers: 6913

Drug and device information, study documents

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