An Overview of Engineered Hydrogel-Based Biomaterials for Improved β-Cell Survival and Insulin Secretion

Abstract

Islet transplantation provides a promising strategy in treating type 1 diabetes as an autoimmune disease, in which damaged β-cells are replaced with new islets in a minimally invasive procedure. Although islet transplantation avoids the complications associated with whole pancreas transplantations, its clinical applications maintain significant drawbacks, including long-term immunosuppression, a lack of compatible donors, and blood-mediated inflammatory responses. Biomaterial-assisted islet transplantation is an emerging technology that embeds desired cells into biomaterials, which are then directly transplanted into the patient, overcoming the aforementioned challenges. Among various biomaterials, hydrogels are the preferred biomaterial of choice in these transplants due to their ECM-like structure and tunable properties. This review aims to present a comprehensive overview of hydrogel-based biomaterials that are engineered for encapsulation of insulin-secreting cells, focusing on new hydrogel design and modification strategies to improve β-cell viability, decrease inflammatory responses, and enhance insulin secretion. We will discuss the current status of clinical studies using therapeutic bioengineering hydrogels in insulin release and prospective approaches.

Keywords: biomaterials; diabetes; hydrogels; insulin secretion; islet encapsulation.

FIGURE 1

Schematic illustrating fabrication steps alginate microcapsules containing human adipose tissue-derived ECM and microencapsulation of pancreatic islets (J. K. Wang J. K. et al., 2020).

FIGURE 2

Methods of microparticles fabrication: (A) batch emulsion technique, (B) microfluidic emulsion technique, and (C) EHD spraying.

FIGURE 3

Cell viability (A) and insulin secretion (B) from hyaluronic acid-alginate hybrid microparticles encapsulating islets (Cañibano-Hernández et al., 2019).

FIGURE 4

Schematic representation of LBL encapsulation of cells. In the direct approach, cells (single or aggregate) are coated by encapsulating materials, whereas, in the indirect approach, cells are initially encapsulated in core materials then covered by LBL self-assembled shells (Liu et al., 2018).

FIGURE 5

Immune-suppressive hydrogels for delivery of β-cells. Cytotoxic T cells around transplantation site deactivated by the release of FasL. This process induces more pancreatic cell survival.

FIGURE 6

(A) The procedure of preparation of micro-patterned collagen sheet as a pancreatic pseudo-tissue and (B) dimensions of hexagonal micro-pattern (Seo et al., 2020).

FIGURE 7

Evaluation of the micro-patterns effect on cellular organization and function. Microscopic images of MIN6 and MS1 co-cultured sheets without (A, D) and with pattern (B, E). Microscopic images of a MIN6 mono-cultured sheet with micro-patterns (C, F). In fluorescence images, MIN6 cells are stained in green, and MS1 cells are stained in red. Cellular clusters are pointed by white dashed circles. (G) Insulin secretion level of MIN6 cells in mono- and co-cultured condition (patterned and non-patterned). Scale bars are 50 μm, and p-value <0.001 indicates significant differences (Seo et al., 2020).

FIGURE 8

Schematic showing oxygen-generating PDMS-CaO₂ disc (A). Photograph of PDMS-CaO₂ disk (10 mm diameter; 1 mm height) (B). Oxygen releasing screening of PDMS- CaO₂ disk (filled diamonds) compared to blank PDMS disk (open diamonds) during 40 days (C) (Pedraza et al., 2012).

FIGURE 9

Schematic view of the βAir I and II implantable bioartificial pancreas devices: (A) cross-section and (B) external view. The β-Air I (C) and β-Air II (D) modules seeded by islets before implantation (Barkai et al., 2013).