Layered PEGDA hydrogel for islet of Langerhans encapsulation and improvement of vascularization

Giulia Marchioli,Lorenzo Moroni,Joao Mano,Karperien Karperien,Eelco De Koning,Marten Engelse,Catarina Oliveira,Aart Van Apeldoorn,Lisa Zellner

doi:10.1007/s10856-017-6004-6

Abstract

Islets of Langerhans need to maintain their round morphology and to be fast revascularized after transplantation to preserve functional insulin secretion in response to glucose stimulation. For this purpose, a non-cell-adhesive environment is preferable for their embedding. Conversely, nutrient and oxygen supply to islets is guaranteed by capillary ingrowth within the construct and this can only be achieved in a matrix that provides adhesion cues for cells. In this study, two different approaches are explored, which are both based on a layered architecture, in order to combine these two opposite requirements. A non-adhesive islet encapsulation layer is based on polyethyleneglycole diacrylate (PEGDA). This first layer is combined with a second hydrogel based on thiolated-gelatin, thiolated-heparin and thiolated-hyaluronic acid providing cues for endothelial cell adhesion and acting as a growth factor releasing matrix. In an alternative approach, a conformal PEGDA coating is covalently applied on the surface of the islets. The coated islets are subsequently embedded in the previously mentioned hydrogel containing thiolated glycosaminoglycans. The suitability of this approach as a matrix for controlled growth factor release has been demonstrated by studying the controlled release of VEGF and bFGF for 14 days. Preliminary tube formation has been quantified on the growth factor loaded hydrogels. This approach should facilitate blood vessel ingrowth towards the embedded islets and maintain islet round morphology and functionality upon implantation.Graphical abstract

Highlights

1.1 Lorenzo Moroni—Reflections on career goalsI was recruited as a Ph.D. student by Isotis Orthobiologics, among the first tissue engineering companies in the world, in 2003 to develop scaffold technologies for osteochondral regeneration
Similar results were achieved in the second approach where islets were modified with a conformal coating of bifunctional PEG, where the SVA group reacted with free amino groups exposed on the surface of the islets and the acryl group on the other extremity of the PEG chain was available for the reaction with acryl groups in the hydrogel matrix
No burst release was shown in the first day of incubation both for Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF)

Summary

Introduction

I was recruited as a Ph.D. student by Isotis Orthobiologics, among the first tissue engineering companies in the world, in 2003 to develop scaffold technologies for osteochondral regeneration. In 2008, I was appointed the Musculoskeletal Tissue Bank R&D director of Rizzoli Orthopedic Institute, where I investigated the use of stem cells from alternative sources and the development of novel biomaterials for skeletal regeneration. These were formative years, where I could sharpen my scientific thinking, expand my hands-on skills, and move the first steps towardsc acquisition for new projects funding. From 2009 till 2014, I joined again Twente University, where I got tenured in the Tissue Regeneration department.

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