PMID- 36723183
OWN - NLM
STAT- MEDLINE
DCOM- 20230315
LR  - 20230315
IS  - 2047-4849 (Electronic)
IS  - 2047-4830 (Linking)
VI  - 11
IP  - 6
DP  - 2023 Mar 14
TI  - Injectable thermosensitive hydrogel to modulate tolerogenic dendritic cells under 
      hyperglycemic condition.
PG  - 2091-2102
LID - 10.1039/d2bm01881k [doi]
AB  - Hyperglycemia associated with diabetes mellitus is a significant risk factor for 
      periodontitis and it polarizes the immune cells towards an inflammatory state. 
      Specific biomaterials can deliver therapeutic or immunomodulatory agents to 
      regulate the excessive periodontal inflammation. Dendritic cells (DCs) bridge the 
      innate and adaptive immune systems and are crucially involved in periodontitis. 
      Thus, targeting DCs is an attractive treatment option for diabetic periodontitis, 
      which, by modulating the downstream adaptive immune cells could regulate the host 
      immune responses. In this study, a chitosan-based thermosensitive injectable 
      self-assembled hydrogel (TISH) was developed to modulate DCs towards a 
      tolerogenic phenotype, which can induce regulatory T-cells to attenuate 
      inflammation and promote healing. Granulocyte-macrophage colony-stimulating 
      factor (GM-CSF) and resveratrol were loaded into TISH (TISH(G + R)) and were 
      sustainably released. TISH demonstrated good biocompatibility and cell 
      penetration in its porous structure. DCs grown in TISH(G + R) under an in vitro 
      hyperglycemic condition showed reduced maturation and activation markers such as 
      CD80, CD83 and CD86, while simultaneously upregulated tolerogenic genes such as 
      FOXP3, SOCS3, TGFss and IL10. Co-culture of these tolerogenic DCs with naive 
      T-cells induced regulatory T-cells differentiation, evidenced by elevated gene 
      expressions of FOXP3, TGFbeta and IL-10. In vivo subcutaneous injection of TISH (G + 
      R) into the mice showed significant infiltration of DCs and regulatory T-cells. 
      In conclusion, TISH was developed and optimized as an injectable hydrogel to 
      modulate DCs towards the tolerogenic phenotype and induce regulatory T-cells 
      under hyperglycemia. TISH has promising potential to improve periodontal 
      parameters in diabetic periodontitis.
FAU - Zhu, Yi
AU  - Zhu Y
AD  - Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON, M5G 
      1G6, Canada. Annie.Shrestha@dentistry.utoronto.ca.
FAU - Winer, Daniel
AU  - Winer D
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 
      King's College Circle, Toronto, ON, M5S 1A8, Canada.
AD  - Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, 
      USA.
AD  - Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto 
      General Hospital Research Institute (TGHRI), University Health Network, Toronto, 
      ON, M5G 1L7, Canada.
AD  - Department of Pathology, University Health Network, Toronto, ON M5G 2C4, Canada.
FAU - Goh, Cynthia
AU  - Goh C
AD  - Department of Chemistry, University of Toronto, 80 George Street, Toronto, ON, 
      M5S 3H6, Canada.
AD  - Department of Materials Science and Engineering, University of Toronto, 84 
      College Street, Toronto, ON, M5S 3E4, Canada.
FAU - Shrestha, Annie
AU  - Shrestha A
AUID- ORCID: 0000-0001-6845-9668
AD  - Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON, M5G 
      1G6, Canada. Annie.Shrestha@dentistry.utoronto.ca.
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 
      King's College Circle, Toronto, ON, M5S 1A8, Canada.
LA  - eng
PT  - Journal Article
DEP - 20230314
PL  - England
TA  - Biomater Sci
JT  - Biomaterials science
JID - 101593571
RN  - 0 (Hydrogels)
RN  - 0 (Forkhead Transcription Factors)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Hydrogels/metabolism
MH  - Inflammation/metabolism
MH  - *Hyperglycemia/metabolism
MH  - Dendritic Cells
MH  - Forkhead Transcription Factors/metabolism
MH  - Cell Differentiation
EDAT- 2023/02/02 06:00
MHDA- 2023/03/16 06:00
CRDT- 2023/02/01 09:28
PHST- 2023/02/02 06:00 [pubmed]
PHST- 2023/03/16 06:00 [medline]
PHST- 2023/02/01 09:28 [entrez]
AID - 10.1039/d2bm01881k [doi]
PST - epublish
SO  - Biomater Sci. 2023 Mar 14;11(6):2091-2102. doi: 10.1039/d2bm01881k.