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Related Experiment Video

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A Multi-Parametric Islet Perifusion System within a Microfluidic Perifusion Device
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Toward a 3D Printed Perfusable Islet Embedding Structure: Technical Notes and Preliminary Results.

Eriselda Keshi1, Peter Tang1, Tobias Lam2

  • 1Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Tissue Engineering. Part C, Methods
|August 2, 2023
PubMed
Summary

This study developed a 3D printed islet embedding structure with a vascular channel for type 1 diabetes treatment. Human islets co-cultured with endothelial progenitor cells successfully engrafted, showing promise for future islet transplantation therapies.

Keywords:
3D printinganastomosabilityislet embedding structureislet transplantationperfusabilitythrombogenicity

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Vascular Engineering

Background:

  • Type 1 diabetes mellitus (T1DM) treatment via islet transplantation faces challenges with long-term engraftment and niche reconstruction.
  • Current islet embedding structures (IESs) are often limited to subcutaneous implantation, hindering vascular integration.
  • 3D printing offers a novel approach to create sophisticated IESs for improved vascularization.

Purpose of the Study:

  • To develop and evaluate a 3D printed islet embedding structure (IES) with an integrated vascular system for potential T1DM treatment.
  • To assess the hemocompatibility, anastomosability, and engraftment potential of the 3D printed IES in a humanized model.
  • To investigate the role of co-culture with endothelial progenitor cells in islet survival and engraftment within the IES.

Main Methods:

  • A proof-of-concept IES was fabricated using 3D printing with biocompatible gelatin methacrylate ink, featuring a branched vascular channel and a central islet cavity.
  • A custom bioreactor was designed for sterile seeding and perfusion experiments under physiological conditions.
  • The IES was tested for hemocompatibility, suture strength, and anastomosability. Engraftment was assessed using rat islets and subsequently human islets co-cultured with human endothelial progenitor cells (huEPCs).

Main Results:

  • The 3D printed IES demonstrated hemocompatibility and anastomosability via cuff anastomosis in an ex vivo perfusion model.
  • While rat islets alone did not survive for 3 days in the structure, human islets co-cultured with huEPCs successfully engrafted within the same timeframe.
  • The vascular channel could be seeded with endothelial cells, and the structure supported co-culture of human islets with huEPCs.

Conclusions:

  • A 3D printed IES with a hemocompatible and potentially anastomosable vascular channel was successfully constructed.
  • Co-culture with nursing cells like huEPCs is crucial for successful human islet engraftment within the 3D printed niche.
  • Further optimization is required to overcome limitations for clinical translation of this 3D printed islet embedding technology.