Document Detail


Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials.
MedLine Citation:
PMID:  22371586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 hypoxia-induced 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.
Authors:
Eileen Pedraza; Maria M Coronel; Christopher A Fraker; Camillo Ricordi; Cherie L Stabler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-27
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-14     Completed Date:  2012-05-08     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4245-50     Citation Subset:  IM    
Affiliation:
Diabetes Research Institute and Departments of Surgery and Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biocompatible Materials / pharmacology*
Calcium Compounds / pharmacology
Cell Death / drug effects
Cell Hypoxia / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Coculture Techniques
Dimethylpolysiloxanes / pharmacology
Hydrolysis / drug effects
Insulin-Secreting Cells / drug effects,  pathology*
Mice
Oxides / pharmacology
Oxygen / pharmacology*
Rats
Sepharose / pharmacology
Time Factors
Grant Support
ID/Acronym/Agency:
DP2 DK083096/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Biocompatible Materials; 0/Calcium Compounds; 0/Dimethylpolysiloxanes; 0/Oxides; 7782-44-7/Oxygen; 9012-36-6/Sepharose; C7X2M0VVNH/lime
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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