期刊
CARBOHYDRATE POLYMERS
卷 302, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2022.120395
关键词
Hyaluronic acid; Glycosignature; 3D bioprinting; Bioresponsive hydrogels; Colorectal cancer models
Aberrant glycosylation events of ECM proteins and cell surface receptors occur in the cancer microenvironment. We developed a protocol to generate 3D bioprinted models of colorectal cancer (CRC) using hyaluronic acid and gelatin functionalized with three specific glycans found in CRC. The glycosylated hydrogels showed good printability, biocompatibility, and stability, and the glycosylation induced diverse alterations in the proteome of tumoroid and surrounding cells.
In cancer microenvironment, aberrant glycosylation events of ECM proteins and cell surface receptors occur. We developed a protocol to generate 3D bioprinted models of colorectal cancer (CRC) crosslinking hyaluronic acid and gelatin functionalized with three signalling glycans characterized in CRC, 3 & PRIME;-Sialylgalactose, 6 & PRIME;-Sialylga-lactose and 2 & PRIME;-Fucosylgalactose. The crosslinking, performed exploiting azide functionalized gelatin and hyaluronic acid and 4arm-PEG-dibenzocyclooctyne, resulted in biocompatible hydrogels that were 3D bioprinted with commercial CRC cells HT-29 and patient derived CRC tumoroids. The glycosylated hydrogels showed good 3D printability, biocompatibility and stability over the time. SEM and synchrotron radiation SAXS/WAXS analysis revealed the influence of glycosylation in the construct morphology, whereas MALDI-MS imaging showed that protein profiles of tumoroid cells vary with glycosylation, indicating that sialylation and fucosylation of ECM proteins induce diverse alterations to the proteome of the tumoroid and surrounding cells.
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