Abstract
Extracellular matrix (ECM) plays an important developmental role by regulating cell behaviour through structural and biochemical stimulation. Tissue-specific ECM, attained through decellularization, has been proposed in several strategies for tissue and organ replacement. Decellularization of animal pancreata has been reported, but the same methods applied to human pancreas are less effective due to higher lipid content. Moreover, ECM-derived hydrogels can be obtained from many decellularized tissues, but methods have not been reported to obtain human pancreas-derived hydrogel. Using novel decellularization methods with human pancreas we produced an acellular, 3D biological scaffold (hP-ECM) and hydrogel (hP-HG) amenable to tissue culture, transplantation and proteomic applications. The inclusion of a homogenization step in the decellularization protocol significantly improved lipid removal and gelation capability of the resulting ECM, which was capable of gelation at 37 °C in vitro and in vivo, and is cytocompatible with a variety of cell types and islet-like tissues in vitro. Overall, this study demonstrates the characterisation of a novel protocol for the decellularization and delipidization of human pancreatic tissue for the production of acellular ECM and ECM hydrogel suitable for cell culture and transplantation applications. We also report a list of 120 proteins present within the human pancreatic matrisome.
Highlights
Biological scaffolds derived from extracellular matrix (ECM) have been widely utilised in regenerative medicine[1,2,3]
Despite continuing advances in insulin delivery technology and recombinant insulins, diabetes and its complications still claim the lives of millions of people, largely due to imperfect long-standing glycaemic control resulting in end-organ complications
The resulting human pancreatic Extracellular matrix (ECM) from both protocols was analysed for lipid removal (Fig. 2)
Summary
Biological scaffolds derived from extracellular matrix (ECM) have been widely utilised in regenerative medicine[1,2,3]. Many envision a tissue engineering solution, via merging a beta cell source, such as stem cell-derived beta cells, with other cellular and matrix components including natural ECM or biomimetic scaffolds, to address this pressing clinical problem. While there are multiple reasons for not recovering pancreata or not transplanting after recovery, numerous organs are available for research through organ procurement organisations We suggest that these pancreata be utilised to study the composition of the human pancreatic ECM, and potentially be used for bioengineering and regenerative medicine purposes. Donor selection is very stringent for pancreas transplant, and as a result many are declined based on medical history, fibrosis, fat deposition and other conservative practises[33] even though the pancreas is healthy and functional These pancreata could be decellularized, processed to construct biomaterials, such as hydrogels, and used for tissue engineering applications rather than be discarded. The high lipid content of non-transplantable human pancreata has posed a barrier to achieving adequate decellularization and hydrogel formation using methods that are typically sufficient for decellularizing lean organs and tissues
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