Mhanna R Kashyap A Palazzolo G Vallmajo-Martin Q Becher J Möller S Schnabelrauch M Zenobi-Wong M 2014 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. application/pdf https://sonar.ch/global/documents/265748 eng info:eu-repo/semantics/altIdentifier/doi/10.1089/ten.TEA.2013.0544 info:eu-repo/semantics/altIdentifier/pmid/24320935 info:eu-repo/semantics/openAccess Tissue engineering. Part A. - 2014 Alginates Animals Batch Cell Culture Techniques Biomimetic Materials Cartilage, Articular Cattle Cell Differentiation Cell Proliferation Cells, Cultured Chondrocytes Chondrogenesis Extracellular Matrix Proteins Glucuronic Acid Hexuronic Acids Sulfates Tissue Engineering Tissue Scaffolds Chondrocyte culture in three dimensional alginate sulfate hydrogels promotes proliferation while maintaining expression of chondrogenic markers. http://purl.org/coar/resource_type/c_6501