Chondrocyte Culture in 3D Alginate Sulfate Hydrogels Promotes, Proliferation While Maintaining Expression of Chondrogenic Markers

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Author(s) Mhanna, Rami, Aditya, Aditya, Palazzolo, Gemma, Vallmajo-Martin, Queralt, Becher, Jana, Schnabelrauch, Matthias, Zenobi-Wong, Marcy, Möller, Stephanie
Publication Type Journal Items, Publication Status: Published
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Title Chondrocyte Culture in 3D Alginate Sulfate Hydrogels Promotes, Proliferation While Maintaining Expression of Chondrogenic Markers
Author(s) Mhanna, Rami
Aditya, Aditya
Palazzolo, Gemma
Vallmajo-Martin, Queralt
Becher, Jana
Schnabelrauch, Matthias
Zenobi-Wong, Marcy
Möller, Stephanie
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 New Rochelle, NY
Publication Place Mary Ann Liebert
Publication Date 2013-06
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 which 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 crosslinkable with calcium chloride. Passage 3 bovine chondrocytes were encapsulated in alginate and alginate sulfate hydrogels for up to 35 days. Cell proliferation was 5-fold higher in alginate sulfate compared to 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 to unmodified alginate, an increase which was blocked by 1 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 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 3D microenvironment which 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 the cell expansion can be done in situ.
Document Type Article
Publication Status Published
Language English
Assigned Organisational Unit(s) 03949
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NEBIS System Number 005837030
Source Database ID FORM-1389870039
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  author = "Mhanna, Rami and Aditya, Aditya and Palazzolo, Gemma and Vallmajo-Martin, Queralt and Becher, Jana and Schnabelrauch, Matthias and Zenobi-Wong, Marcy and M{\"{o}}ller, Stephanie",
  title = "{C}hondrocyte {C}ulture in 3{D} {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 = 2013,
  volume = "20",
  number = "9/10",
  pages = "1454--1464",
  month = jun,

E-Citations record created: Thu, 16 Jan 2014, 11:01:09 CET