Oxygen generating scaffolds for enhancing engineered tissue survival

Oh, Se Heang; Ward, Catherine L.; Atala, Anthony; Yoo, James J.; Harrison, Benjamin S.

doi:10.1016/j.biomaterials.2008.09.065

Cited by 270 publications

(266 citation statements)

References 25 publications

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“…Removal of PDMSCaO 2 disks from treated groups reinforces the theory that the observed enhancements are due solely to oxygen release and not due to an artifact or initial shielding from hypoxia. It should also be noted that no free radical or peroxide scavenging materials were used in this study, in contrast to other published reports using solid peroxides in which catalase was used for all experimental studies (17).…”

Section: Discussionmentioning

confidence: 94%

“…Limiting or eliminating the hypoxic period between implantation and the development of a fully functional, intradevice, vascular network would dramatically reduce hypoxia-induced cell death and permit for more clinically translatable devices. Such methods include prevascularization of the transplant site (12), hastening vascularization through the delivery of growth factors (13,14), incorporation of oxygen carriers within biomaterials (15), or the in situ generation of supplemental oxygen (16)(17)(18)(19). In situ oxygen generation is a highly desirable approach, in that it does not require multiple surgeries and provides supplemental oxygen immediately upon implantation.…”

mentioning

confidence: 99%

“…Encapsulation of solid peroxide within a polymer could serve to temper its hydrolytic reactivity. A solid peroxide platform using films of poly (lactic-co-glycolic acid) (PLGA) has been published, whereby the oxygen-generating potential of these materials was shown through enhanced fibroblast proliferation and reduced necrosis in a skin flap mouse model (16,17). The benefit of the films, however, was short lived, and the reaction kinetics were less controlled owing to the hydrolytic degradation of the PLGA.…”

mentioning

confidence: 99%

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

Pedraza

Coronel

Fraker

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

358

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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

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Pedraza

Coronel

Fraker

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

358

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“…Control over oxygen tension and its manipulation appears to be a powerful tool with which to program the function and fate of MSCs, ultimately enabling control over their behavior in a clinical setting. Biomaterials that are designed either to release oxygen to stimulate cell survival or to mimic hypoxia to stimulate angiogenesis may, in fact, act as instructive materials for controlled differentiation of mesenchymal progenitor cells into cartilage and bone (27,28).…”

Section: Discussionmentioning

confidence: 99%

Metabolic programming of mesenchymal stromal cells by oxygen tension directs chondrogenic cell fate

Leijten¹,

Georgi²,

Teixeira³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

112

114

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Actively steering the chondrogenic differentiation of mesenchymal stromal cells (MSCs) into either permanent cartilage or hypertrophic cartilage destined to be replaced by bone has not yet been possible. During limb development, the developing long bone is exposed to a concentration gradient of oxygen, with lower oxygen tension in the region destined to become articular cartilage and higher oxygen tension in transient hypertrophic cartilage. Here, we prove that metabolic programming of MSCs by oxygen tension directs chondrogenesis into either permanent or transient hyaline cartilage. Human MSCs chondrogenically differentiated in vitro under hypoxia (2.5% O 2 ) produced more hyaline cartilage, which expressed typical articular cartilage biomarkers, including established inhibitors of hypertrophic differentiation. In contrast, normoxia (21% O 2 ) prevented the expression of these inhibitors and was associated with increased hypertrophic differentiation. Interestingly, gene network analysis revealed that oxygen tension resulted in metabolic programming of the MSCs directing chondrogenesis into articular-or epiphyseal cartilage-like tissue. This differentiation program resembled the embryological development of these distinct types of hyaline cartilage. Remarkably, the distinct cartilage phenotypes were preserved upon implantation in mice. Hypoxia-preconditioned implants remained cartilaginous, whereas normoxia-preconditioned implants readily underwent calcification, vascular invasion, and subsequent endochondral ossification. In conclusion, metabolic programming of MSCs by oxygen tension provides a simple yet effective mechanism by which to direct the chondrogenic differentiation program into either permanent articular-like cartilage or hypertrophic cartilage that is destined to become endochondral bone.tissue engineering | chondral defects | skeletogenesis | cell therapy | regenerative medicine

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“…56,57 For example, fluorinated compounds 58 or peroxides have been incorporated into scaffolds to enable the controlled release of oxygen. 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.…”

Section: Conductive Hydrogelsmentioning

confidence: 99%