期刊
BIOMATERIALS
卷 29, 期 34, 页码 4521-4531出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2008.08.008
关键词
Disulfide-containing crosslinkers; Thiol-disulfide exchange reaction; Synthetic extracellular matrix; In situ crosslinking; Primary cells; Hyaluronic acid
资金
- NSF FIBR [EF-0526854]
- State of Utah Centers of Excellence Program
- NIH [2 R01 DC04336]
- NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS [R01DC004336] Funding Source: NIH RePORTER
An unmet need for expansion of primary cells and progenitor cells in three dimensions (3-D) is a synthetic mimic of the extracellular matrix (ECM) with user-controllable composition that would permit rapid recovery of viable cells under mild, non-enzymatic conditions. Three block copolymers based on disulfide-containing polyethylene glycol diacrylate crosslinkers were synthesized, and were used to crosslink thiol-modified hyaluronan and gelatin macromonomers in the presence of cells. The triblock PEGSSDA contained a single disulfide-containing block, the pentablock PEG(SS)(2)DA contained two disulfide blocks, and the heptablock PEG(SS)(3)DA contained three disulfide blocks. For each hydrogel composition, four cell types were encapsulated in 3-D, and growth and proliferation were evaluated. Murine NIH 3T3 fibroblasts, human HepG2 C3A hepatocytes, human bone marrow-derived mesenchymal stem cells (MSCs), and human umbilical vein endothelial cells (HUVECs) all showed excellent viability and growth during expansion in 3-D in the three disulfide block copolymer crosslinkers. After cell expansion, the hydrogels were dissociated using the thiol-disulfide exchange reaction in the presence of N-acetyl-cysteine or glutathione, which dissolved the hydrogel network. After dissolution, cells were recovered in high yield and with high viability by gentle centrifugation. (C) 2008 Elsevier Ltd. All rights reserved.
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