OxySite – Oxygen Generating Biomaterial
While accelerating vascularization of the implant is highly desirable, there is always a hypoxic period between implantation and the development of a fully functional, intra-device, vascular network. Limiting or eliminating this hypoxic period would dramatically reduce hypoxia-induced cell death and permit for more clinically translatable devices, particularly for islets, which not only express high oxygen demand but are also sensitive to hypoxic stress. As such, we developed an in situ oxygen generating biomaterial to provide supplemented oxygen immediately upon implantation, called OxySite. Through manipulation of the material properties, we were able to develop a means to provide controlled and temporal oxygen to the microenvironment for extended time periods. These results of this work were recently published in the Proceedings for the National Academy of Science. In this study, we illustrated the potential of this system to eliminate hypoxia-induced cell dysfunction and death for both a highly proliferating cell line and primary rat pancreatic islets. This system was highly efficacious is supplementing oxygen to the cells, in both culture and within 3-D constructs. Future studies are focused on translating this system in vivo. The impact of this novel biomaterial is not strictly limited to islets; given the generality of this platform, the translation of these materials to other cell-based implants, as well as ischemic tissues in general, is envisioned.
Efforts in this area are currently being supported by the JDRF by the projects:
“Engineered Bioactive Hydrogel Macrodevices for Islet Transplantation: Engineering an Optimal Site for Islet Transplantation”, a collaborative project with Drs Camillo Ricordi, Luca Inverardi, Rodolfo Alejandro, Alice Tomei, and Dora Berman-Weinberg.
“Development of an Extrahepatic Site for Beta Cell Replacement without Continuous, Systemic Immunosuppression”, a collaborative project with Dr. Andres Garcia