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Diabetic wound regeneration using peptide-modified hydrogels to target re-epithelialization.
Xiao, Yun; Reis, Lewis A; Feric, Nicole; Knee, Erica J; Gu, Junhao; Cao, Shuwen; Laschinger, Carol; Londono, Camila; Antolovich, Julia; McGuigan, Alison P; Radisic, Milica.
Afiliação
  • Xiao Y; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
  • Reis LA; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
  • Feric N; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
  • Knee EJ; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
  • Gu J; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.
  • Cao S; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.
  • Laschinger C; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
  • Londono C; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
  • Antolovich J; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • McGuigan AP; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
  • Radisic M; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Toronto General Research Institute, University Health Network, Toronto, ON M5G 2C4,
Proc Natl Acad Sci U S A ; 113(40): E5792-E5801, 2016 10 04.
Article em En | MEDLINE | ID: mdl-27647919
There is a clinical need for new, more effective treatments for chronic wounds in diabetic patients. Lack of epithelial cell migration is a hallmark of nonhealing wounds, and diabetes often involves endothelial dysfunction. Therefore, targeting re-epithelialization, which mainly involves keratinocytes, may improve therapeutic outcomes of current treatments. In this study, we present an integrin-binding prosurvival peptide derived from angiopoietin-1, QHREDGS (glutamine-histidine-arginine-glutamic acid-aspartic acid-glycine-serine), as a therapeutic candidate for diabetic wound treatments by demonstrating its efficacy in promoting the attachment, survival, and collective migration of human primary keratinocytes and the activation of protein kinase B Akt and MAPKp42/44 The QHREDGS peptide, both as a soluble supplement and when immobilized in a substrate, protected keratinocytes against hydrogen peroxide stress in a dose-dependent manner. Collective migration of both normal and diabetic human keratinocytes was promoted on chitosan-collagen films with the immobilized QHREDGS peptide. The clinical relevance was demonstrated further by assessing the chitosan-collagen hydrogel with immobilized QHREDGS in full-thickness excisional wounds in a db/db diabetic mouse model; QHREDGS showed significantly accelerated and enhanced wound closure compared with a clinically approved collagen wound dressing, peptide-free hydrogel, or blank wound controls. The accelerated wound closure resulted primarily from faster re-epithelialization and increased formation of granulation tissue. There were no observable differences in blood vessel density or size within the wound; however, the total number of blood vessels was greater in the peptide-hydrogel-treated wounds. Together, these findings indicate that QHREDGS is a promising candidate for wound-healing interventions that enhance re-epithelialization and the formation of granulation tissue.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos / Hidrogéis / Diabetes Mellitus Experimental / Reepitelização Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos / Hidrogéis / Diabetes Mellitus Experimental / Reepitelização Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Canadá