PMID- 19426107
OWN - NLM
STAT- MEDLINE
DCOM- 20100120
LR  - 20181201
IS  - 1937-335X (Electronic)
IS  - 1937-3341 (Linking)
VI  - 15
IP  - 11
DP  - 2009 Nov
TI  - Addition of hyaluronic acid to alginate embedded chondrocytes interferes with 
      insulin-like growth factor-1 signaling in vitro and in vivo.
PG  - 3449-59
LID - 10.1089/ten.TEA.2009.0069 [doi]
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.
FAU - Yoon, Diana M
AU  - Yoon DM
AD  - Department of Chemical and Biomolecular Engineering, University of Maryland, 
      College Park, Maryland 20742, USA.
FAU - Curtiss, Shane
AU  - Curtiss S
FAU - Reddi, A Hari
AU  - Reddi AH
FAU - Fisher, John P
AU  - Fisher JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Tissue Eng Part A
JT  - Tissue engineering. Part A
JID - 101466659
RN  - 0 (Alginates)
RN  - 0 (Hexuronic Acids)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 8A5D83Q4RW (Glucuronic Acid)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Alginates/*chemistry
MH  - Animals
MH  - Cattle
MH  - Cell Culture Techniques/methods
MH  - Cells, Cultured
MH  - Chondrocytes/cytology/drug effects/*metabolism
MH  - Chondrogenesis/drug effects/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Glucuronic Acid/chemistry
MH  - Hexuronic Acids/chemistry
MH  - Hyaluronic Acid/*administration & dosage
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Signal Transduction/drug effects/*physiology
MH  - Tissue Engineering/*methods
EDAT- 2009/05/12 09:00
MHDA- 2010/01/21 06:00
CRDT- 2009/05/12 09:00
PHST- 2009/05/12 09:00 [entrez]
PHST- 2009/05/12 09:00 [pubmed]
PHST- 2010/01/21 06:00 [medline]
AID - 10.1089/ten.TEA.2009.0069 [doi]
PST - ppublish
SO  - Tissue Eng Part A. 2009 Nov;15(11):3449-59. doi: 10.1089/ten.TEA.2009.0069.