Integrating Additive Manufacturing Techniques to Improve Cell‐Based Implants for the Treatment of Type 1 Diabetes

Abstract

The increasing global prevalence of endocrine diseases like type 1 diabetes mellitus (T1DM) elevates the need for cellular replacement approaches, which can potentially enhance therapeutic durability and outcomes. Central to any cell therapy is the design of delivery systems that support cell survival and integration. In T1DM, well-established fabrication methods have created a wide range of implants, ranging from 3D macro-scale scaffolds to nano-scale coatings. These traditional methods, however, are often challenged by their inherent limitations in reproducible and discrete fabrication, particularly when scaling to the clinic. Additive manufacturing (AM) techniques provide a means to address these challenges by delivering improved control over construct geometry and microscale component placement. While still early in development in the context of T1DM cellular transplantation, the integration of AM approaches serves to improve nutrient material transport, vascularization efficiency, and the accuracy of cell, matrix, and local therapeutic placement. This review highlights current methods in T1DM cellular transplantation and the potential of AM approaches to overcome these limitations. In addition, emerging AM technologies and their broader application to cell-based therapy are discussed. Cellular Implants for the Treatment of Type 1 DiabetesCell-based therapies provide a potential curative approach for resolving type 1 diabetes mellitus (T1DM) via the replacement of the insulin-producing cells lost to autoimmune destruction. [1][2][3] In the native pancreas, these insulin-producing cells, termed 𝛽-cells, work to modulate metabolism and blood sugar in

Vascularization in Bioartificial Parenchymal Tissue: Bioink and Bioprinting Strategies

“…Bioprinting is a broad term to describe the primarily layer-by-layer deposition of biocompatible or biodegradable materials together with integrated cells and therapy agents [ 13 , 23 ]. Although not the focus of this review, a brief introduction to state-of-the-art bioprinting technologies is provided to aid the understanding of specific bioink strategies and their relation to vascularization processes ( Figure 1 b–d).…”

“…The specific printing features of this technology are similar to conventional 2D inkjet printing. Low-viscosity bioinks can be deposited at high speed and with high precision [ 13 , 14 , 23 ]. The diameter of the ink droplets ranges from 10 to 150 µm [ 1 , 20 ].…”

“…Thus, compared to inkjet bioprinting, microextrusion enables the bioprinting of viscous formulations and higher cell densities [ 13 , 17 ]. However, viscous material deposition can also cause higher shear stress with a negative impact on cell viability [ 16 , 21 , 23 , 31 , 32 ]. Crosslinking can be achieved chemically, thermally, by ultraviolet (UV) light, or based on shear-thinning properties of the bioink.…”

“…In parenchymal organ replacement therapy, all constructs need to be scaled to dimensions that need endogenous perfusion systems to achieve the necessary number of cells [ 15 , 18 , 21 , 22 ]. Thus, a major limitation central to any cell therapy approach is the establishment of perfusing vascularization in a TEP that supports cell survival, integration, and function [ 4 , 7 , 13 , 15 , 22 , 23 ]. At this moment, the objective is twofold: (i) acceleration of the process towards an anastomosis between bioartificial graft and host vasculature and (ii) the establishment of sufficient intragraft vascular density.…”

“…At this moment, the objective is twofold: (i) acceleration of the process towards an anastomosis between bioartificial graft and host vasculature and (ii) the establishment of sufficient intragraft vascular density. The extensive vascularization of bioartificial tissue is a prerequisite for the long-term function of most transplanted cells [ 23 ]. Technological advancements such as three-dimensional (3D) bioprinting have led to intensified research interest in this interdisciplinary field [ 7 ].…”