Abstract

Cell microencapsulation is an attractive strategy for cell-based therapies that allows the implantation of genetically engineered cells and the continuous delivery of de novo produced therapeutic products. However, the establishment of a way to retrieve the implanted encapsulated cells in case the treatment needs to be halted or when cells need to be renewed is still a big challenge. The combination of micro and macroencapsulation approaches could provide the requirements to achieve a proper immunoisolation, while maintaining the cells localized into the body. We present the development and characterization of a porous implantable macrocapsule device for the loading of microencapsulated cells. The device was fabricated in polyamide by selective laser sintering (SLS), with controlled porosity defined by the design and the sintering conditions. Two types of microencapsulated cells were tested in order to evaluate the suitability of this device; erythropoietin (EPO) producing C2C12 myoblasts and Vascular Endothelial Growth Factor (VEGF) producing BHK fibroblasts. Results showed that, even if the metabolic activity of these cells decreased over time, the levels of therapeutic protein that were produced and, importantly, released to the media were stable.

Highlights

  • Bioactive cell encapsulation has emerged as a promising tool for the treatment of patients with various chronic disorders including diabetes mellitus, central nervous system diseases, and cardiovascular diseases[1,2,3,4]

  • Concerning the metabolic activity of the encapsulated Baby hamster kidney (BHK)-Vascular Endothelial Growth Factor (VEGF) fibroblasts, the activity is reduced drastically after the first week in D1 and D2, and later on, in D3, to the results showed for C2C12-EPO myoblasts

  • We have combined the microencapsulation technology with the use of an external macro-device fabricated by selective laser sintering (SLS), as an approach to maintain the microcapsules at the implantation site, and improve the biosecurity of this technology

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Summary

Introduction

Bioactive cell encapsulation has emerged as a promising tool for the treatment of patients with various chronic disorders including diabetes mellitus, central nervous system diseases, and cardiovascular diseases[1,2,3,4]. Other approaches relay on the pre-vascularization of larger pore size (∼5 μm) polymeric implanted devices[20,21], or cavities[22,23], before cells allocation, combined with the use of systemic immunosuppression to prevent the host immune system from attacking the transplanted cells. With this approach, Theracyte device and the Sernova Cell Pouch, have reached clinical trials to restore pancreatic function[8,24]. 3D printing techniques have become a promising, cheap, and simple tool for scaffold and devices fabrication by using biocompatible materials with on-demand design and porosity[25,26]

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