The Role of the Pancreatic Extracellular Matrix as a Tissue Engineering Support for the Bioartificial Pancreas

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic condition primarily managed with insulin replacement, leading to significant treatment costs. Complications include vasculopathy, cardiovascular diseases, nephropathy, neuropathy, and reticulopathy. Pancreatic islet transplantation is an option but its success does not depend solely on adequate vascularization. The main limitations to clinical islet transplantation are the scarcity of human pancreas, the need for immunosuppression, and the inadequacy of the islet isolation process. Despite extensive research, T1DM remains a major global health issue. In 2015, diabetes affected approximately 415 million people, with projected expenditures of USD 1.7 trillion by 2030. Pancreas transplantation faces challenges due to limited organ availability and complex vascularization. T1DM is caused by the autoimmune destruction of insulin-producing pancreatic cells. Advances in biomaterials, particularly the extracellular matrix (ECM), show promise in tissue reconstruction and transplantation, offering structural and regulatory functions critical for cell migration, differentiation, and adhesion. Tissue engineering aims to create bioartificial pancreases integrating insulin-producing cells and suitable frameworks. This involves decellularization and recellularization techniques to develop biological scaffolds. The challenges include replicating the pancreas's intricate architecture and maintaining cell viability and functionality. Emerging technologies, such as 3D printing and advanced biomaterials, have shown potential in constructing bioartificial organs. ECM components, including collagens and glycoproteins, play essential roles in cell adhesion, migration, and differentiation. Clinical applications focus on developing functional scaffolds for transplantation, with ongoing research addressing immunological responses and long-term efficacy. Pancreatic bioengineering represents a promising avenue for T1DM treatment, requiring further research to ensure successful implementation.

Keywords: decellularization; diabetes mellitus; extracellular matrix; insulin-producing cells; tissue engineering.

Figure 1

Diabetic complications and their systemic impacts. Diabetes can lead to severe complications affecting multiple organs and systems. Diabetic retinopathy compromises the retinal blood vessels, potentially leading to vision loss. Diabetic nephropathy causes progressive kidney damage, resulting in renal failure. Diabetic ulcers, particularly in the feet, occur due to poor circulation and neuropathy, which can result in amputations. The diabetic pancreas has impaired insulin production. Diabetic neuropathies include peripheral neuropathy, causing pain and loss of sensation in the limbs, and autonomic neuropathy, which affects involuntary functions such as digestion and blood pressure regulation. These complications underscore the importance of maintaining good glycemic control to prevent further systemic damage.

Figure 2

The image illustrates the various therapeutic methods aimed at restoring insulin production in diabetic patients, such as pancreatic transplantation, islet infusion, and the use of cellular drugs. In addition to tissue engineering, the decellularization process aims to address the shortage of organs for patients in need of transplants.