Extracellular Matrix Scaffold Technology for Bioartificial Pancreas Engineering

Abstract

Emergent technologies in regenerative medicine may soon overcome the limitations of conventional diabetes therapies. Collaborative efforts across the subfields of stem cell technology, islet encapsulation, and biomaterial carriers seek to produce a bioengineered pancreas capable of restoring endocrine function in patients with insulin-dependent diabetes. These technologies rely on a robust understanding of the extracellular matrix (ECM), the supportive 3-dimensional network of proteins necessary for cellular attachment, proliferation, and differentiation. Although these functions can be partially approximated by biosynthetic carriers, novel decellularization protocols have allowed researchers to discover the advantages afforded by the native pancreatic ECM. The native ECM has proven to be an optimal platform for recellularization and whole-organ pancreas bioengineering, an exciting new field with the potential to resolve the dire shortage of transplantable organs. This review seeks to contextualize recent findings, discuss current research goals, and identify future challenges of regenerative medicine as it applies to diabetes management.

The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas

“…4,18,25 The importance of transitioning to human organs is obvious in the context of clinical relevance. Our results indicate that whole discarded human pancreata can be consistently and successfully decellularized through detergent-based perfusion methodology.…”

A Perspective on the Clinical Translation of Scaffolds for Tissue Engineering

“…Specifically, the decellularization of organs with reseeding of cells has been utilized to generate a variety of functional whole organs, including bladder, heart, lung, liver, skin, trachea, esophagus, and kidney. 26,80,81,83,92,100,107 While decellularized organs have potential as highly controlled tissue scaffolds, several considerations must be addressed before these become clinically viable options for organ transplant. Scale-up and translation of current methods to human-sized organs is beginning to be explored.…”

Bioengineering for Organ Transplantation: Progress and Challenges

“…34 Islet encapsulation aims to isolate implanted islet cells from the recipient immune response by hiding the non-self antigens. Unfortunately, difficulties with biocompatibility of capsule materials, inadequate immunoisolation and poor vascularization have limited successful clinical translation.…”

“…Unfortunately, difficulties with biocompatibility of capsule materials, inadequate immunoisolation and poor vascularization have limited successful clinical translation. 34 Biomaterial carriers involve the use of bioartificial scaffolds that mimic native ECM to allow seeding of pluripotent cells and have yielded promising initial results. 34 The decellularization-recellularization approach has since been applied to the pancreas.…”

“…34 Biomaterial carriers involve the use of bioartificial scaffolds that mimic native ECM to allow seeding of pluripotent cells and have yielded promising initial results. 34 The decellularization-recellularization approach has since been applied to the pancreas. Successful decellularization and recellularization of mouse pancreata with both endocrine and exocrine cells has been achieved, with cell types displaying appropriate functionality (C-peptide and amylase secretion respectively) and differentiating in their appropriate locations.…”