PF127/bleomycin hydrogel promotes subcutaneous extracellular matrix remodeling and fibrosis to construct personalized flaps through the TGFß-Col signaling pathway.
Immunopharmacol Immunotoxicol
; 46(5): 695-702, 2024 Oct.
Article
in En
| MEDLINE
| ID: mdl-39164805
ABSTRACT
BACKGROUND:
Skin flap transplantation is used to effectively reconstruct defects of the hand and foot skin and soft tissues. We here investigated the effect of the PF127/bleomycin (BLM) hydrogel on the extracellular matrix (ECM) remodeling of skin flaps and the underlying mechanism, thereby providing a new reference point for personalized flap modification and overcoming abrasion resistance- and stability-associated difficulties.METHODS:
The appropriate PF127/BLM concentration was selected based on the gelation time and drug release curve. Migration assays, scratch assays, and live/dead staining were conducted to verify the effect of PF127/BLM on human skin fibroblasts (HSFs). The effects of PF127/BLM on the ECM were assessed through hematoxylin and eosin and Masson staining. Additionally, we examined the expression of ECM remodeling-related genes and proteins involved in their associated signaling pathway. Finally, the effects of PF127/BLM on organ fibrosis and toxicity to liver and kidney functions were assessed in mice.RESULTS:
A 25% PF127/BLM hydrogel was selected as the study concentration. PF127/BLM augmented HSF chemotaxis and proliferation. Furthermore, PF127/BLM promoted subcutaneous ECM remodeling and fibrosis, increased the flap dermis thickness, and reduced the toxic side effects of BLM on liver/lung fibrosis and liver/kidney function. Additional studies confirmed that the PF127/BLM-mediated regulation of ECM remodeling in skin flaps was associated with TGFß-Col signaling pathway activation.CONCLUSION:
The PF127/BLM hydrogel promoted subcutaneous ECM remodeling and fibrosis, which aided the construction of personalized flaps through the TGFß-Col signaling pathway, with decreased hepatic, pulmonary, and renal toxicities.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bleomycin
/
Signal Transduction
/
Transforming Growth Factor beta
/
Hydrogels
/
Extracellular Matrix
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Immunopharmacol Immunotoxicol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
TOXICOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United kingdom