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In situ oxygen delivery to cellular transplants via hydrolytically activated biomaterials

Eileen Pedraza^1,2, Maria Coronel^1,2, Camillo Ricordi^1,2,3, Cherie Stabler^1,2,3

¹Biomedical Engineering; ²Diabetes Research Institute; ³Department of Surgery, University of Miami, Miami, FL, United States

The implantation of cellular transplants within avascaular sites is hampered by inadequate oxygen delivery. The inevitable delay in angiogenesis following implantation results in substantial cell loss. Islets transplantation is particularly susceptible to functional impairment at moderate oxygen tensions. Herein, we developed an oxygen generating biomaterial to supplement oxygen, to bridge the lag between cellular implantation and development of an adequate vascular network.

Oxygen generating disks (OXY-SIL) were fabricated by mixing calcium peroxide with PDMS polymer and curing within molds to form disks, rods, or sponges. Oxygen production was assessed via sealed chambers/sensors. Cell studies co-incubated MIN6 or islets (human or rat) with OXY-SIL, cultured at either normal (20%) or hypoxic (5%) oxygen. Cell viability and insulin secretion were assessed.

We found that the oxygen generative capacity of the biomaterial could be modulated via the peroxide concentration and total polymer volume or surface area. For example, OXY-SIL sponges produced oxygen for ~2 weeks (minimum of 100 mmHg/day), while OXY-SIL disks produced oxygen for over 40 days (minimum of 100 mmHg/day). Co-culture of MIN6 cells or islets under hypoxic conditions with OXY-SIL resulted in ~2-fold increase in viability over hypoxic controls, with viability comparable to normoxic controls (p<0.05). Islets cultured in hypoxic conditions demonstrated significant insulin dysfunction, while islets incubated with OXY-SIL exhibited insignificant changes.

We have established the ability to fabricate a biomaterial capable of providing optimal, sustainable, and controllable delivery of oxygen. Encapsulation of solid peroxide within hydrophobic PDMS shielded the surrounding milieu from the peroxide and any detrimental degradation by-products. Enhanced cell viability and function for beta cell lines and islets was observed when incubated with OXY-SIL at hypoxic conditions. Given the ubiquitous need for optimal oxygen delivery within implants, we believe this material can provide benefit to numerous cell transplants.

The authors acknowledge JDRFI, DRIF, and NIH support.