Abstract
The development of an engineered tissue requires a clear understanding of the interactions between the individual components. In this study, we investigated how the addition of hyaluronic acid (HA) to a cartilage tissue engineered scaffold alters chondrocytic expression, and specifically the expression of insulin-like growth factor-1 (IGF-1) signaling molecules. Bovine chondrocytes were embedded (7 million cells/mL) in 2.0% w/v alginate hydrogels containing varying HA concentrations (0, 0.05, 0.50, and 5.00 mg/mL). In vitro constructs were cultured with exogenous IGF-1, and gene expression was monitored at days 1, 4, and 8 for IGF-1, IGF-1 receptor (IGF-1R), IGF binding protein 3 (IGFBP-3), type II collagen and type I collagen. In vivo constructs were precultured for 24 h with exogenous IGF-1 before being implanted subcutaneously in severe combined immunodeficient mice; samples were analyzed using histology at days 7, 14, and 21. Results indicate that, with the addition of high levels (5.00 mg/mL) of HA, IGF-1 can become entrapped within the matrix and therefore interfere with the delivery of IGF-1 to chondrocytes. In vitro and in vivo data showed that increasing the concentration of HA in an alginate hydrogel can decrease chondrocyte IGF-1 expression. IGF-1R expression did not change with HA concentration, and the addition of any HA did not significantly alter IGFBP-3 expression. Chondrocytes continuously expressed phenotypic type II collagen in vitro and in vivo throughout the study for all the groups. However, for all the HA concentrations investigated, chondrocytes showed more of a fibroblastic phenotype, as indicated by greater expression of type I collagen than with no HA, in vitro and in vivo. In conclusion, these results indicate that HA interferes with the delivery of IGF-1 to chondrocytes, affecting the endogenous expression of IGF-1 signaling molecules and the resulting chondrocyte phenotype, and therefore demonstrating the critical effect of biomaterial scaffolds on encapsulated cell function.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3449-3459 |
| Number of pages | 11 |
| Journal | Tissue Engineering - Part A |
| Volume | 15 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2009 |
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ASJC Scopus subject areas
- Bioengineering
- Biochemistry
- Biomedical Engineering
- Biomaterials
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Addition of hyaluronic acid to alginate embedded chondrocytes interferes with insulin-like growth factor-1 signaling in vitro and in vivo. / Yoon, Diana M.; Curtiss, Shane; Reddi, A Hari; Fisher, John P.
In: Tissue Engineering - Part A, Vol. 15, No. 11, 01.11.2009, p. 3449-3459.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Addition of hyaluronic acid to alginate embedded chondrocytes interferes with insulin-like growth factor-1 signaling in vitro and in vivo
AU - Yoon, Diana M.
AU - Curtiss, Shane
AU - Reddi, A Hari
AU - Fisher, John P.
PY - 2009/11/1
Y1 - 2009/11/1
N2 - The development of an engineered tissue requires a clear understanding of the interactions between the individual components. In this study, we investigated how the addition of hyaluronic acid (HA) to a cartilage tissue engineered scaffold alters chondrocytic expression, and specifically the expression of insulin-like growth factor-1 (IGF-1) signaling molecules. Bovine chondrocytes were embedded (7 million cells/mL) in 2.0% w/v alginate hydrogels containing varying HA concentrations (0, 0.05, 0.50, and 5.00 mg/mL). In vitro constructs were cultured with exogenous IGF-1, and gene expression was monitored at days 1, 4, and 8 for IGF-1, IGF-1 receptor (IGF-1R), IGF binding protein 3 (IGFBP-3), type II collagen and type I collagen. In vivo constructs were precultured for 24 h with exogenous IGF-1 before being implanted subcutaneously in severe combined immunodeficient mice; samples were analyzed using histology at days 7, 14, and 21. Results indicate that, with the addition of high levels (5.00 mg/mL) of HA, IGF-1 can become entrapped within the matrix and therefore interfere with the delivery of IGF-1 to chondrocytes. In vitro and in vivo data showed that increasing the concentration of HA in an alginate hydrogel can decrease chondrocyte IGF-1 expression. IGF-1R expression did not change with HA concentration, and the addition of any HA did not significantly alter IGFBP-3 expression. Chondrocytes continuously expressed phenotypic type II collagen in vitro and in vivo throughout the study for all the groups. However, for all the HA concentrations investigated, chondrocytes showed more of a fibroblastic phenotype, as indicated by greater expression of type I collagen than with no HA, in vitro and in vivo. In conclusion, these results indicate that HA interferes with the delivery of IGF-1 to chondrocytes, affecting the endogenous expression of IGF-1 signaling molecules and the resulting chondrocyte phenotype, and therefore demonstrating the critical effect of biomaterial scaffolds on encapsulated cell function.
AB - The development of an engineered tissue requires a clear understanding of the interactions between the individual components. In this study, we investigated how the addition of hyaluronic acid (HA) to a cartilage tissue engineered scaffold alters chondrocytic expression, and specifically the expression of insulin-like growth factor-1 (IGF-1) signaling molecules. Bovine chondrocytes were embedded (7 million cells/mL) in 2.0% w/v alginate hydrogels containing varying HA concentrations (0, 0.05, 0.50, and 5.00 mg/mL). In vitro constructs were cultured with exogenous IGF-1, and gene expression was monitored at days 1, 4, and 8 for IGF-1, IGF-1 receptor (IGF-1R), IGF binding protein 3 (IGFBP-3), type II collagen and type I collagen. In vivo constructs were precultured for 24 h with exogenous IGF-1 before being implanted subcutaneously in severe combined immunodeficient mice; samples were analyzed using histology at days 7, 14, and 21. Results indicate that, with the addition of high levels (5.00 mg/mL) of HA, IGF-1 can become entrapped within the matrix and therefore interfere with the delivery of IGF-1 to chondrocytes. In vitro and in vivo data showed that increasing the concentration of HA in an alginate hydrogel can decrease chondrocyte IGF-1 expression. IGF-1R expression did not change with HA concentration, and the addition of any HA did not significantly alter IGFBP-3 expression. Chondrocytes continuously expressed phenotypic type II collagen in vitro and in vivo throughout the study for all the groups. However, for all the HA concentrations investigated, chondrocytes showed more of a fibroblastic phenotype, as indicated by greater expression of type I collagen than with no HA, in vitro and in vivo. In conclusion, these results indicate that HA interferes with the delivery of IGF-1 to chondrocytes, affecting the endogenous expression of IGF-1 signaling molecules and the resulting chondrocyte phenotype, and therefore demonstrating the critical effect of biomaterial scaffolds on encapsulated cell function.
UR - http://www.scopus.com/inward/record.url?scp=72649093558&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=72649093558&partnerID=8YFLogxK
U2 - 10.1089/ten.tea.2009.0069
DO - 10.1089/ten.tea.2009.0069
M3 - Article
C2 - 19426107
AN - SCOPUS:72649093558
VL - 15
SP - 3449
EP - 3459
JO - Tissue Engineering - Part A
JF - Tissue Engineering - Part A
SN - 1937-3341
IS - 11
ER -