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.

Type 1 Diabetes Mellitus: A Review on Advances and Challenges in Creating Insulin Producing Devices

“…Popular types of scaffolds include hydrogels and inert matrices such as porous polystyrene membranes [ 83 ]. Some of these materials have been reviewed elsewhere [ 84 ]. Another prominent approach of 3D modeling is using organoid technology or scaffold-free 3D-cell culture methods, where cells self-assemble into clusters or spheroids.…”

Bioengineering the Vascularized Endocrine Pancreas: A Fine-Tuned Interplay Between Vascularization, Extracellular-Matrix-Based Scaffold Architecture, and Insulin-Producing Cells

“…The use of ECM-derived components along with a wise design of bioengineered systems might be a good alternative strategy to match and functionally integrate these two features into unique bioengineered scaffolds, allowing the amelioration of both graft vascularization and endocrine viability and activity ( 22 , 112 ). 3D bio-printing technologies can be suitable for achieving tailored bioengineering devices for β-cell replacement, offering the following opportunities: 1) tuning the 3D spatial deposition of different cell types simultaneously, 2) encapsulation of cellular components within different hydrogel preparations, and 3) customizing the scaffold architecture according to the requested function ( 22 , 98 , 192 ) ( Figure 2 ).…”

Leverage biomaterials to modulate immunity for type 1 diabetes

“…Pancreatic infiltrated islet-autoreactive T cells destroy the β-cells, resulting in insufficient insulin secretion, that elicits hyperglycemia ( 2 ). T1D is commonly occurred in children and adolescents with age from 1 to 15 years old, and around 1.2 million cases worldwide are diagnosed with T1D by 2021 ( 3 ). Moreover, the incidence of T1D is rising ever year.…”

“…Moreover, the incidence of T1D is rising ever year. There are annually almost 30,000 new cases in United States and 13,000 new cases in China ( 3 ).…”

“…Shapiro and colleagues successfully performed islet transplant on a patient firstly in 2000, and this standard procedure was known as “Edmon protocol” ( 8 ). Although islet transplantation can be technically achieved, it still faces many problems such as the lack of donors, cumbersome isolation of islets, immune rejection of transplantation, long-term need for immunosuppressants, and islet death caused by immune rejection and hypoxia ( 3 ). To conquer these issues, utilizing biomaterial to encapsulate islets, β-cells or induced pluripotent stem cells enhances our insight into better transplantation in remission of autoimmune responses, amelioration of hypoxia and protection against fibrosis.…”