Chondrocyte Culture in Three Dimensional Alginate Sulfate Hydrogels Promotes Proliferation While Maintaining Expression of Chondrogenic Markers

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Author(s) Mhanna, Rami, Kashyap, Aditya, Palazzolo, Gemma, Vallmajo-Martin, Queralt, Becher, Jana, Möller, Stephanie, Schnabelrauch, Matthias, Zenobi-Wong, Marcy
Publication Type Journal Items, Publication Status: Published
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Title Chondrocyte Culture in Three Dimensional Alginate Sulfate Hydrogels Promotes Proliferation While Maintaining Expression of Chondrogenic Markers
Author(s) Mhanna, Rami
Kashyap, Aditya
Palazzolo, Gemma
Vallmajo-Martin, Queralt
Becher, Jana
Möller, Stephanie
Schnabelrauch, Matthias
Zenobi-Wong, Marcy
Journal or Series Title Tissue engineering. Part A
Volume Number 20
Issue Number 9-10
Start Page 1454
End Page 1464
ISSN 1937-3341
Publisher Mary Ann Liebert
Publication Place New Rochelle, NY
Publication Date 2014-05-01
Abstract The loss of expression of chondrogenic markers during monolayer expansion remains a stumbling block for cell-based treatment of cartilage lesions. Here, we introduce sulfated alginate hydrogels as a cartilage biomimetic biomaterial that induces cell proliferation while maintaining the chondrogenic phenotype of encapsulated chondrocytes. Hydroxyl groups of alginate were converted to sulfates by incubation with sulfur trioxide–pyridine complex (SO3/pyridine), yielding a sulfated material cross-linkable with calcium chloride. Passage 3 bovine chondrocytes were encapsulated in alginate and alginate sulfate hydrogels for up to 35 days. Cell proliferation was five-fold higher in alginate sulfate compared with alginate (p=0.038). Blocking beta1 integrins in chondrocytes within alginate sulfate hydrogels significantly inhibited proliferation (p=0.002). Sulfated alginate increased the RhoA activity of chondrocytes compared with unmodified alginate, an increase that was blocked by β1 blocking antibodies (p=0.017). Expression and synthesis of type II collagen, type I collagen, and proteoglycan was not significantly affected by the encapsulation material evidenced by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Alginate sulfate constructs showed an opaque appearance in culture, whereas the unmodified alginate samples remained translucent. In conclusion, alginate sulfate provides a three dimensional microenvironment that promotes both chondrocyte proliferation and maintenance of the chondrogenic phenotype and represents an important advance for chondrocyte-based cartilage repair therapies providing a material in which cell expansion can be done in situ.
DOI 10.1089/ten.tea.2013.0544
Additional Notes Received 31 August 2013, Accepted 2 December 2013
Document Type Article
Publication Status Published
Language English
Assigned Organisational Unit(s) 03949
Organisational Unit(s)
NEBIS System Number 005837030
Source Database ID SCOPUS-84899822692
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  author = "Mhanna, Rami and Kashyap, Aditya and Palazzolo, Gemma and Vallmajo-Martin, Queralt and Becher, Jana and M{\"{o}}ller, Stephanie and Schnabelrauch, Matthias and Zenobi-Wong, Marcy",
  title = "{C}hondrocyte {C}ulture in {T}hree {D}imensional {A}lginate {S}ulfate {H}ydrogels {P}romotes {P}roliferation {W}hile {M}aintaining {E}xpression of {C}hondrogenic {M}arkers",
  journal = "Tissue engineering. Part A",
  year = 2014,
  volume = "20",
  number = "9-10",
  pages = "1454--1464",
  month = may,

E-Citations record created: Tue, 03 Jun 2014, 07:17:28 CET