A Collagen Based Cryogel Bioscaffold that Generates Oxygen for Islet Transplantation

Abstract

The aim of this article is to develop, characterize, and test a novel 3D bioscaffold matrix that can accommodate pancreatic islets and provide them with a continuous, controlled, and steady source of oxygen to prevent hypoxia-induced damage following transplantation. Hence, a collagen-based cryogel bioscaffold that incorporates calcium peroxide (CPO) into its matrix is made. The optimal concentration of CPO integrated into bioscaffolds is 0.25 wt% and this generates oxygen at 0.21 ± 0.02 × 10 -3 m day -1 (day 1), 0.19 ± 0.01 × 10 -3 m day -1 (day 6), 0.13 ± 0.03 × 10 -3 m d -1 (day 14), and 0.14 ± 0.02 × 10 -3 m d -1 (day 21). Accordingly, islets seeded into cryogel-CPO bioscaffolds have a significantly higher viability and function compared to islets seeded into cryogel alone bioscaffolds; these findings are supported by data from quantitative computational modeling. When syngeneic islets are transplanted into the epididymal fat pad (EFP) of diabetic mice, the cryogel-0.25 wt%CPO bioscaffold improves islet function with diabetic animals re-establishing glycemic control. Mice transplanted with cryogel-0.25 wt%CPO bioscaffolds show faster responses to intraperitoneal glucose injections and have a higher level of insulin content in their EFP compared to those transplanted with islets alone (P < 0.05). The novel oxygen-generating bioscaffold (i.e., cryogel-0.25 wt%CPO) therefore provides a biostable and biocompatible 3D microenvironment for islets which can facilitate islet survival and function at extra-hepatic sites of transplantation.

Development of a Bioartificial Vascular Pancreas

“… 86 , 87 Other technologies aim to seed islets with oxygen-generating scaffolds to improve oxygen availability immediately post-transplantation. 35 , 88 Development of these types of techniques to improve oxygen availability highlights the need to prevent hypoxia in transplanted islets.…”

Localized drug delivery graphene bioscaffolds for cotransplantation of islets and mesenchymal stem cells

“…While the subcutaneous space can be easily accessed for bioscaffold implantation, the omentum also has several promising attributes, which include its large well-vascularized surface area (61). Both sites also have the ability to accommodate 3D bioscaffolds (11,39,40), as well as the ability to retrieve these platforms should something adverse happen. Furthermore, human clinical trials are already under way examining the feasibility of the omentum as a site for PDMSbased bioscaffolds for islet transplantation (61).…”

“…Every week, bioscaffolds were removed from PBS, dried overnight, and reweighed [dry weight ( W d2 )]. The degree of bioscaffold biodegradation was calculated as follows: [( W d1 − W d2 )/ W d1 × 100] ( 11 ).…”

“…Bioscaffolds are rapidly gaining attraction for islet transplantation (6)(7)(8)(9)(10)(11)(12) given that they contain pores that can accommodate islets while simultaneously offering a unique interface that can be modulated to solve several problems currently faced by islets in the immediate posttransplantation period (such as inflammation) (13). Bioscaffolds have predominantly been made from synthetic polymers, including polydimethylsiloxane (PDMS) (7), poly(lactide-co-glycolide) (6), poly(d,l-lactide-co-e-caprolactone) (8), poly(ethylene oxide terephtalate)/poly(butylene terephthalate) block copolymer (9), and heparin-binding peptide amphiphiles (10).…”

Design and Assessment of Biodegradable Macroporous Cryogels as Advanced Tissue Engineering and Drug Carrying Materials

“…Due to this, collagen is often a favorable material for the development of a tissue scaffold that mimics the ECM environment and promotes cell proliferation and differentiation. A collagen-based cryogel was prepared by cross-linking with EDC/NHS [ 103 , 104 ]. Coating with polydopamine increased the viability (by 52%) and proliferation (by 33%) of mesenchymal stem cells in dopamine-modified collagen cryogels compared to non-modified ones [ 103 ].…”