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International Journal of Bioprinting Biofabrication for islet transplantation

1. Introduction methods can serve as novel tools for promoting
vascularization and immune defense, thereby facilitating
Pancreatic islets, composed of endocrine and insulin- successful islet transplantation.
producing beta cells, are diminutive cellular aggregates
situated within the pancreas. In type 1 diabetes (T1D), also This review provides an overview of recent advances
referred to as insulin-dependent or juvenile diabetes, the in biomaterials and biofabrication technologies for
immune system specifically targets and annihilates beta engineering cell delivery systems aimed at enhancing
cells, leading to impaired insulin production. Intensive the efficacy of islet transplantation (Figure 1). First,
insulin therapy presents itself as a viable solution that we elucidated the pivotal components crucial for the
efficaciously ameliorates the regulation of blood glucose success of islet transplantation, with a specific emphasis
levels and mitigates the risk of subsequent complications, on the immune protection and vascularization strategies
such as neuropathy, nephropathy, retinopathy, and employed for optimal islet delivery. Subsequently, we
cardiovascular ailments. Despite intensive insulin therapy, a offer a brief overview of the key biomaterials used in
subset of patients with unstable T1D experience challenges islet transplantation, underscoring their importance in
in sustaining glycemic control through insulin injections. implementing the full potential of islet delivery systems.
Hypoglycemia is a prevalent occurrence in individuals with In addition, we discuss recent biofabrication technologies
diabetes, irrespective of the diabetes type, particularly among leveraged for the development of islet delivery systems.
those undergoing insulin therapy . Unmitigated severe Finally, we present an outlook on the future prospects
[1]
hypoglycemic incidents can precipitate adverse outcomes, and challenges in the field of cell delivery systems for islet
such as unconsciousness, convulsions, and fatality. transplantation.

In contrast, pancreatic islet transplantation has
emerged as a viable therapeutic alternative for individuals 2. Critical considerations for islet
with T1D who exhibit inadequate glucose control or transplantation
insulin-induced hypoglycemia [2-4] . Islet transplantation 2.1. Immunosuppression
decreases hemoglobin A1c levels, reduces the risk of Islet transplantation has recently garnered considerable
diabetic complications, and eliminates the requirement for attention due to advancements in islet isolation
exogenous insulin, which is closely linked to an improved technology and immunosuppressive treatments . The islet
[9]
quality of life . Although islet transplantation is a
[5]
promising treatment for diabetes, it has certain challenges, transplantation approach in clinical practice involves the
such as susceptibility to the cellular microenvironment infusion of islets into the patient’s liver through the portal
vein. However, the transplantation site presents a non-ideal
and vulnerable environments and immune-hostile environment characterized by high glucose concentrations,
[6]
[7]
conditions . Additionally, the transplantation site and low oxygen levels, and other unfavorable factors.
surrounding environment often differ from those of
natural islets, posing a significant obstacle to the success of Furthermore, infusion of islets through the hepatic portal
insulin-producing cells. Revascularization, which involves vein elicits an immediate blood-mediated inflammatory
the diffusion of oxygen, nutrients, metabolic waste, reaction. In addition, hypoxic islets secrete chemokines and
and insulin, is crucial for the proper functioning of the express tissue factors that initiate thrombotic responses.
transplanted islets. Subsequently, platelets are recruited to the islet surface,
attracting leukocytes and macrophages that infiltrate the
To address these challenges, current approaches, such as islet cells and lead to their destruction. Hence, several
oxygenation with supplemental biomaterials, co-culturing challenges associated with islet transplantation remain,
with vascular cells, treatment with immunosuppressive including suboptimal efficiency of cell delivery, inadequate
drugs, and encapsulation of islets, are being actively islet functionality and viability, restricted transplant
explored. In particular, biomaterial-based biofabrication, construct volume, and high dosages of immunosuppressive
which is considered a potential solution to overcome drugs post-transplantation [10-12] . These obstacles impede
current problems, is under investigation. the efficacy of islet transplantation, primarily because of
Biomaterials are usually designed to mimic the the host immune response against the transplanted cells
biochemical and biophysical properties of the natural and the insufficient or absent vascularization, ultimately
extracellular matrix (ECM), thereby providing a leading to compromised survival and functionality of
supportive environment for cells to thrive. Enhancing the islets. To circumvent these limitations, researchers
interactions between cells and biomaterials can improve are pursuing novel strategies such as immune evasion
cellular function, maturation, and signal transduction . mechanisms or promoting vascularization to improve islet
[8]
Consequently, suitable biomaterials and biofabrication engraftment and functionality.

Volume 9 Issue 6 (2023) 392 https://doi.org/10.36922/ijb.1024