Comprehensive biocompatibility profiling of human pancreas-derived biomaterial

Amish Asthana^1,2,3*Eva Amanda Gallego Suárez⁴Tamara Lozano⁴Lori N Byers^1,2,5Jun Ho-Heo²Wonwoo Jeong²Riccardo Tamburrini^2,5Arunkumar Rengaraj^1,2,5Deborah Chaimov^2,5Quentin Perrier^1,2,5,6Alice Tomei⁷Christopher A Fraker⁷Sang Jin Lee^2,5Giuseppe Orlando^1,2,5*

• ¹Department of Surgery, Wake Forest Baptist Medical Center, Medical Center Boulevard, Winston-Salem, United States
• ²Wake Forest Institute for Regenerative Medicine, Winston-Salem, United States
• ³Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, United States
• ⁴Nanoimmunotech, Vigo, Spain
• ⁵School of Medicine, Wake Forest University, Winston-Salem, United States
• ⁶Univ. Grenoble Alpes, Pharmacy Department, Grenoble Alpes University Hospital, Grenoble, France
• ⁷Diabetes Research Institute, University of Miami, Miami, United States

The importance of the extracellular matrix (ECM) to pancreatic islets has been clearly demonstrated, as isolated islets grown in culture or transplanted, quickly lose viability and function after their matrix associations have been stripped away during the isolation process. Therefore, recapitulating the islet niche is a critical objective to move the field of islet transplantation forward. As a first step to recreating the islet microenvironment, we have recently developed a detergent-free decellularization method to obtain a decellularized solubilized ECM (dsECM) powder from human pancreas. We have also shown that this gentler method (compared to traditional detergent-based methods) allows for thorough preservation of the molecular fingerprint of the innate organ. Furthermore, incorporation of dsECM in alginatemicroencapsulated human islets, showed a significant increase in insulin secretion, compared to both free and alginate-only encapsulated islets. However, it is also essential to test the interaction of dsECM with multiple cell types to establish its safety for transplantation. Herein, we present a comprehensive in vitro evaluation of the cytotoxicity, hemocompatibility and immunocompatibility of dsECM to establish a concentration range where it deemed safe and biocompatible. Furthermore, dsECM-based bioinks were coaxially bioprinted and the resulting construct's biocompatibility and vascularization potential were also evaluated in vivo.