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Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice
Published on: July 23, 2017
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Prevascularized Retrievable Hybrid Implant to Enhance Function of Subcutaneous Encapsulated Islets
Auvro R Mridha1,2,3, Tim R Dargaville4, Paul D Dalton5
1Discipline of Physiology, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, Australia.
Tissue Engineering. Part A
|October 21, 2020
Summary
This study developed a 3D printed scaffold with microencapsulated pancreatic cells to treat type 1 diabetes without immunosuppression. The hybrid device successfully lowered blood glucose in diabetic mice, showing promise for future human therapies.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Diabetes Research
Background:
- Type 1 diabetes (T1D) treatment often requires toxic immunosuppressive drugs for pancreatic β-cell replacement.
- Developing effective and safe β-cell therapies without antirejection drugs is crucial for T1D management.
Purpose of the Study:
- To create a bioengineered hybrid device for allogeneic β-cell transplantation without immunosuppression.
- To evaluate the efficacy of microencapsulated β-cells within 3D printed scaffolds in normalizing blood glucose levels in diabetic mouse models.
Main Methods:
- Fabrication of a hybrid device using 3D polycaprolactone (PCL) scaffolds printed via melt electrospin writing (MEW) and alginate microencapsulated mouse β-cells (MIN6 and QS islets).
- Subcutaneous implantation of the hybrid devices into streptozotocin-treated diabetic NOD/SCID and BALB/c mice.
- Assessment of blood glucose levels (BGL), glucose tolerance, graft vascularization (3D-Doppler ultrasound), and host immune response.
Main Results:
- Implanted hybrid devices normalized BGL in diabetic mice within 25-41 days, with enhanced normalization (60-105 days) in prevascularized scaffolds.
- 3D-Doppler ultrasound confirmed a linear increase in graft vascularity over 4 weeks.
- Histological examination revealed inflammatory infiltrates on scaffolds but not on microcapsules, indicating minimal host rejection.
Conclusions:
- A retrievable, 3D printed hybrid device promotes vascularization and enhances survival of encapsulated islets for T1D treatment without immunosuppression.
- The study provides proof-of-concept for potential human application, though modifications are needed for long-term efficacy.
