期刊
ACTA BIOMATERIALIA
卷 10, 期 2, 页码 843-857出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2013.09.040
关键词
Chitosan derivatives; Wound dressings; Diabetic foot ulcers; Neurotensin; Wound healing
资金
- COMPETE
- FEDER
- Fundacao para a Ciencia e Tecnologia (FCT-MEC) [PTDC/SAU-MII/098567/2008, PTDC/SAU FAR/121109/2010, PEst-C/EQB/UI0102/2011, PEst-C/SAU/LA0001/2013-2014]
- FCT-MEC [SFRH/BD/60837/2009, SFRH/BPD/40409/2007, SFRH/BPD/46341/2008]
- Fundação para a Ciência e a Tecnologia [PEst-C/EQB/UI0102/2011, PTDC/SAU-FAR/121109/2010, PTDC/SAU-MII/098567/2008] Funding Source: FCT
One important complication of diabetes mellitus is chronic, non-healing diabetic foot ulcers (DFUs). This study aims to develop and use dressings based on chitosan derivatives for the sustained delivery of neurotensin (NT), a neuropeptide that acts as an inflammatory modulator in wound healing. Three different derivatives, namely N-carboxymethyl chitosan, 5-methyl pyrrolidinone chitosan (MPC) and N-succinyl chitosan, are presented as potential biomaterials for wound healing applications. Our results show that MPC has the best fluid handling capacity and delivery profile, also being non-toxic to Raw 264.7 and HaCaT cells. NT-loaded and non-loaded MPC dressings were applied to control/diabetic wounds to evaluate their in vitro/in vivo performance. The results show that the former induced more rapid healing (50% wound area reduction) in the early phases of wound healing in diabetic mice. A NT-loaded MPC foam also reduced expression of the inflammatory cytokine TNF-alpha, (P < 0.001) and decreased the amount of inflammatory infiltrate on day 3. On day 10 MMP-9 was reduced in diabetic skin (P < 0.001), significantly increasing fibroblast migration and collagen (COL1A1, COL1A2 and COL3A1) expression and deposition. These results suggest that MPC-based dressings may work as an effective support for sustained NT release to reduce DFUs. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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