Maturation of Pancreatic Spheroids within Macroencapsulation Devices to Tissue-Like Structures by a 3D-Printed...

Islet transplantation in type 1 diabetes confronts challenges, including isolation-induced islet damage, hypoxia, re-emergence of autoimmunity, and foreign body reactions. Pre-transplant conditioning strategies that support physiological homeostasis while protecting islets within encapsulation devices are therefore essential. We developed electrospun hydrophilic cellulose acetate (eCA) membranes and hydrophobic polytetrafluoroethylene (ePTFE) membranes with nano-topographical surfaces for islet encapsulation. They were tested for protein adsorption and macrophage activation, while eCA and ePTFE devices were evaluated by encapsulating MIN6 spheroids to assess their encapsulation efficiency and Glucose-stimulated insulin secretion (GSIS) capability. Furthermore, the devices encapsulating MIN6 spheroids were tested for 14 days in a custom 3D-printed bioreactor with continuous dynamic flow. Both eCA and ePTFE membranes restricted the entry or attachment of activated macrophages. The cells encapsulated in eCA-devices released significantly more insulin than those in ePTFE-devices, reflected by higher stimulation indices, suggesting the nutrient transfer ability of eCA. Under dynamic conditions, the encapsulated spheroids in eCA-devices were associated with high viability (80% at day 7 and 98% at day 14) and underwent initial compaction followed by tissue-like structure formation. Microscopy and immunofluorescence revealed the presence of ECM proteins, collagen-1, and E-cadherin, supporting the compaction and remodeling. These results demonstrate that the bioreactor system may be utilised as a pre-transplantation conditioning platform to rehabilitate isolated islets within encapsulated devices.