State of the Art of Bioengineering Approaches in Beta-Cell Replacement

Abstract

Purpose of the review: Despite recent advancements in technology for the treatment of type 1 diabetes (T1D), exogenous insulin delivery through automated devices remains the gold standard for treatment. This review will explore progress made in pancreatic islet bioengineering within the field of beta-cell replacement for T1D treatment.

Recent findings: First, we will focus on the use of decellularized extracellular matrices (dECM) as a platform for pancreatic organoid development. These matrices preserve microarchitecture and essential biochemical signals for cell differentiation, offering a promising alternative to synthetic matrices. Second, advancements in 3D bioprinting for creating complex organ structures like pancreatic islets will be discussed. This technology allows for increased precision and customization of cellular models, crucial for replicating native pancreatic islet functionality. Finally, this review will explore the use of stem cell-derived organoids to generate insulin-producing islet-like cells. While these organoids face challenges such as functional immaturity and poor vascularization, they represent a significant advancement for disease modeling, drug screening, and autologous islet transplantation.

Summary: These innovative approaches promise to revolutionize T1D treatment by overcoming the limitations of traditional therapies based on human pancreatic islets.

Keywords: Bioengineering; Bioprinting; Extracellular matrix; Islet on a chip; Islets; Type 1 diabetes.

Fig. 1

Decellularization process. a In order for decellularized tissue to remain hypoimmunogenic, it is important to make sure that native intracellular components such as DNA have been removed while ECM remains intact. b As described, methods that use detergents, enzymes, and mechanical force all contribute to the overall decellularization of whole tissue. c ECM contains integral membrane and structural proteins such as laminin, collagen, and fibronectin. DNA: deoxyribonucleic acid, ECM: extracellular matrix

Fig. 2

Bioprinting extrusion based. Bioprinting involves several different parameters which must be closely controlled to achieve the ideal construct which is suitable for therapeutic applications. These parameters include, but are not limited to, pressure, speed, resolution, bioink viscosity, and temperature. The bioink which encapsulates cells such as islets as shown is also paramount to the success of bioprinting. The extrusion method such as a piston, screw, pneumatic (air), or coaxial method is also an important consideration and determinant in resulting viability of cells within the cell-laden construct

Fig. 3

Coaxial printing. Depiction of core–shell model produced by coaxial bioprinting. The interior core houses the islets, ECM, and other growth factors. The shell serves as an immunoprotective layer wherein angiogenic factors are preserved and T-regulatory cells may be kept, while also preventing immunological agents from reaching the protected islets. All figures were created with Biorender.com