In several pathological conditions, including diabetic foot and bedsores, efficient wound healing is hampered by hypoxia, altering the release from surrounding cells of molecules involved in matrix turn-over (matrix metalloproteinases, MMPs; tissue inhibitors of metalloproteinases, TIMPs). Interestingly, impaired chronic wounds might be effectively targeted by new oxygenating drugs such as O2-Loaded Nanobubbles (OLNs). In the present work, the effects of hypoxia on MMP/TIMP secretion from human keratinocytes (HaCaT cell line) were investigated, and the therapeutic potential of chitosan-shelled decafluoropentane-containing OLNs was evaluated. Normoxic keratinocytes released basal MMP-2, MMP-9, TIMP-1 and TIMP-2 protein levels. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9 and TIMP-2 without affecting TIMP-1 release. Chitosan OLNs, characterized by spherical morphology, diameters of 700 nm and cationic surfaces, were avidly internalized by keratinocytes, not displaying cell cytotoxicity and not affecting cell viability. After internalization, OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring normoxic balances. Neither O2-saturated solution (OSS) nor O2-free nanobubbles (OFNs) did mimic OLN abilities, suggesting that they were specifically dependent on time-protracted O2 diffusion from OLN core. Collectively, these data show that chitosan OLNs can effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Thus topical administration of exogenous O2, properly encapsulated in nanobubble formulations, could be a promising approach to promote healing processes in chronic wounds.

Chitosan oxygen-loaded nanobubbles counteract hypoxia dysregulation of MMP/TIMP balances in human keratinocytes: new perspectives for chronic wound healing.

KHADJAVI, AMINA;ARGENZIANO, MONICA;GULINO, GIULIA ROSSANA;GIRIBALDI, Giuliana;CAVALLI, Roberta;GUIOT, Caterina;PRATO, Mauro
2013-01-01

Abstract

In several pathological conditions, including diabetic foot and bedsores, efficient wound healing is hampered by hypoxia, altering the release from surrounding cells of molecules involved in matrix turn-over (matrix metalloproteinases, MMPs; tissue inhibitors of metalloproteinases, TIMPs). Interestingly, impaired chronic wounds might be effectively targeted by new oxygenating drugs such as O2-Loaded Nanobubbles (OLNs). In the present work, the effects of hypoxia on MMP/TIMP secretion from human keratinocytes (HaCaT cell line) were investigated, and the therapeutic potential of chitosan-shelled decafluoropentane-containing OLNs was evaluated. Normoxic keratinocytes released basal MMP-2, MMP-9, TIMP-1 and TIMP-2 protein levels. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9 and TIMP-2 without affecting TIMP-1 release. Chitosan OLNs, characterized by spherical morphology, diameters of 700 nm and cationic surfaces, were avidly internalized by keratinocytes, not displaying cell cytotoxicity and not affecting cell viability. After internalization, OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring normoxic balances. Neither O2-saturated solution (OSS) nor O2-free nanobubbles (OFNs) did mimic OLN abilities, suggesting that they were specifically dependent on time-protracted O2 diffusion from OLN core. Collectively, these data show that chitosan OLNs can effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Thus topical administration of exogenous O2, properly encapsulated in nanobubble formulations, could be a promising approach to promote healing processes in chronic wounds.
2013
Get Connected!3– 3rd Wellcome Trust Centre for Cell-Matrix Research Conference 2013
Manchester, UK
11-13/09/2013
Get Connected!3– 3rd Wellcome Trust Centre for Cell-Matrix Research Conference 2013 - Abstract book
Wellcome Trust Centre for Cell-Matrix Research
29
29
A. Khadjavi; C. Magnetto; A. Panariti; M. Argenziano; G.R. Gulino; I. Rivolta; G. Giribaldi; A. Troia; R. Cavalli; C. Guiot; M. Prato
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/138949
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