PMID- 25871410
OWN - NLM
STAT- MEDLINE
DCOM- 20160304
LR  - 20181202
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Linking)
VI  - 16
IP  - 6
DP  - 2015 Jun 8
TI  - Hyaluronic Acid Based Hydrogels Attenuate Inflammatory Receptors and 
      Neurotrophins in Interleukin-1beta Induced Inflammation Model of Nucleus Pulposus 
      Cells.
PG  - 1714-25
LID - 10.1021/acs.biomac.5b00168 [doi]
AB  - Inflammation plays an important role in symptomatic intervertebral disc 
      degeneration and is associated with the production of neurotrophins in 
      sensitizing innervation into the disc. The use of high molecular weight (HMw) 
      hyaluronic acid (HA) hydrogels offers a potential therapeutic biomaterial for 
      nucleus pulposus (NP) regeneration as it exerts an anti-inflammatory effect and 
      provides a microenvironment that is more suitable for NP. Therefore, it was 
      hypothesized that cross-linked HMw HA hydrogels modulate the inflammatory 
      receptor of IL-1R1, MyD88 and neurotrophin expression of nerve growth factor 
      (NGF) and brain-derived neurotrophic factor (BDNF) in an in vitro inflammation 
      model of NP. HA cross-linking was optimized using various concentrations of 4-arm 
      PEG-amine by determination of free carboxyl groups of HA and unreacted free amine 
      groups of PEG-amine. The optimally cross-linked HA hydrogels were characterized 
      for hydrolytic stability, enzymatic degradation and cytotoxicity on NP cells. The 
      therapeutic effect of HA hydrogels was further investigated in IL-1beta induced 
      inflammation on NP cell cultures and the mechanism of HA by examining the 
      expression of cell surface receptor of CD44. Hydrogel was optimally cross-linked 
      at 75 mM PEG, stable in phosphate buffered saline, and showed greater than 40% 
      resistance to enzymatic degradation. No cytotoxic effect of NP cells was observed 
      in the presence of hydrogels for 1, 3, and 7 days. IL-1R1 and MyD88 were 
      significantly suppressed. Additionally, NGF and BDNF mRNA were down-regulated 
      after treatment with cross-linked HA hydrogel. Possible protective mechanism of 
      HA is shown by high expression of CD44 receptor of NP cells after HA treatment in 
      which suggest the binding of HA to CD44 receptor and prevent NP cells from 
      further undergoing inflammation. These results indicate that optimally stabilized 
      cross-linked HMw HA hydrogel has a therapeutic effect in response to 
      inflammation-associated pain and becomes an ideal matrices hydrogel for NP 
      regeneration.
FAU - Isa, Isma Liza Mohd
AU  - Isa IL
AD  - daggerCentre for Research in Medical Devices (CURAM) and double daggerCentre for Microscopy and 
      Imaging, National University of Ireland, Galway, Ireland.
FAU - Srivastava, Akshay
AU  - Srivastava A
AD  - daggerCentre for Research in Medical Devices (CURAM) and double daggerCentre for Microscopy and 
      Imaging, National University of Ireland, Galway, Ireland.
FAU - Tiernan, David
AU  - Tiernan D
AD  - daggerCentre for Research in Medical Devices (CURAM) and double daggerCentre for Microscopy and 
      Imaging, National University of Ireland, Galway, Ireland.
FAU - Owens, Peter
AU  - Owens P
AD  - daggerCentre for Research in Medical Devices (CURAM) and double daggerCentre for Microscopy and 
      Imaging, National University of Ireland, Galway, Ireland.
FAU - Rooney, Peadar
AU  - Rooney P
AD  - daggerCentre for Research in Medical Devices (CURAM) and double daggerCentre for Microscopy and 
      Imaging, National University of Ireland, Galway, Ireland.
FAU - Dockery, Peter
AU  - Dockery P
AD  - daggerCentre for Research in Medical Devices (CURAM) and double daggerCentre for Microscopy and 
      Imaging, National University of Ireland, Galway, Ireland.
FAU - Pandit, Abhay
AU  - Pandit A
AD  - daggerCentre for Research in Medical Devices (CURAM) and double daggerCentre for Microscopy and 
      Imaging, National University of Ireland, Galway, Ireland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150505
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Hydrogels)
RN  - 0 (Interleukin-1)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptors, Interleukin-1)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Animals
MH  - Cartilage/*drug effects/metabolism
MH  - Cattle
MH  - Cells, Cultured
MH  - Hyaluronic Acid/chemistry/*pharmacology
MH  - Hydrogels/chemistry/*pharmacology
MH  - Inflammation/metabolism
MH  - Interleukin-1/*pharmacology
MH  - Intervertebral Disc/drug effects
MH  - Myeloid Differentiation Factor 88/*metabolism
MH  - Nerve Growth Factors/genetics/*metabolism
MH  - Polyethylene Glycols/chemistry
MH  - Receptors, Interleukin-1/*metabolism
EDAT- 2015/04/15 06:00
MHDA- 2016/03/05 06:00
CRDT- 2015/04/15 06:00
PHST- 2015/04/15 06:00 [entrez]
PHST- 2015/04/15 06:00 [pubmed]
PHST- 2016/03/05 06:00 [medline]
AID - 10.1021/acs.biomac.5b00168 [doi]
PST - ppublish
SO  - Biomacromolecules. 2015 Jun 8;16(6):1714-25. doi: 10.1021/acs.biomac.5b00168. 
      Epub 2015 May 5.