Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials

Abstract

A major hindrance in engineering tissues containing highly metabolically active cells is the insufficient oxygenation of these implants, which results in dying or dysfunctional cells in portions of the graft. The development of methods to increase oxygen availability within tissue-engineered implants, particularly during the early engraftment period, would serve to allay hypoxiainduced cell death. Herein, we designed and developed a hydrolytically activated oxygen-generating biomaterial in the form of polydimethylsiloxane (PDMS)-encapsulated solid calcium peroxide, PDMS-CaO 2 . Encapsulation of solid peroxide within hydrophobic PDMS resulted in sustained oxygen generation, whereby a single disk generated oxygen for more than 6 wk at an average rate of 0.026 mM per day. The ability of this oxygen-generating material to support cell survival was evaluated using a β cell line and pancreatic rat islets. The presence of a single PDMS-CaO 2 disk eliminated hypoxia-induced cell dysfunction and death for both cell types, resulting in metabolic function and glucose-dependent insulin secretion comparable to that in normoxic controls. A single PDMS-CaO 2 disk also sustained enhanced β cell proliferation for more than 3 wk under hypoxic culture conditions. Incorporation of these materials within 3D constructs illustrated the benefits of these materials to prevent the development of detrimental oxygen gradients within large implants. Mathematical simulations permitted accurate prediction of oxygen gradients within 3D constructs and highlighted conditions under which supplementation of oxygen tension would serve to benefit cellular viability. 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.tissue engineering | encapsulation | bioartificial pancreas | diabetes

Avoiding Immunosuppression for Islet Transplantation: Use of Protective Biomaterials

“…Addition of the angiogenic factor, fibroblast growth factor 1 (FGF-1), into capsule was able to affect a continuous FGF-1 release for a 1-month period in vitro [57]. In another study, encapsulation of solid peroxide within polydimethylsiloxane resulted in sustained oxygen release from the matrix for approximately 6 weeks [58].…”

THERAPY OF ENDOCRINE DISEASE: Islet transplantation for type 1 diabetes: so close and yet so far away

“…Encapsulation of solid peroxide in polydimethylsiloxane (PDMS) as a hydrophobic polymer reduces the rate of hydration and provides sustained release of oxygen. Through this approach, metabolic function and glucose-dependent insulin secretion of the MIN6 cell line and islet cells under hypoxic in vitro conditions have been retained (135).…”

“…During isolation and early post-transplantation, providing oxygen solely by gradient-driven passive diffusion results in decreasing oxygen pressure in islets radially from the periphery to the core (131). Different strategies suggested to overcome the hypoxia challenge include hyperbaric oxygen (HBO) therapy (132), design of gas permeable devices (133), oxygen carrier agents (134) and in situ oxygen generators (135). Hyperbaric oxygen therapy has been shown to mitigate hypoxic conditions during early post-islet transplantation in recipient animals frequently exposed to high pressure oxygen.…”

Hydrogels for cardiac tissue engineering

“…51,59 Such 3D biomimetic materials can be fabricated in the form of thin polymer films, 60 electrospun fibers, 61 porous scaffolds 62 and hydrogels. 63,64 The use of oxygen-releasing materials is particularly useful for providing sufficient amount of oxygen, especially during the early stages of in vitro cultures and in vivo implants. 56,65 Thus, such systems may be beneficial for regeneration of damaged or diseased cardiac tissues.…”