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Carbohydr Polym. 2016 May 20;142:114-23. doi: 10.1016/j.carbpol.2016.01.045. Epub 2016 Jan 22.

Peptide-decorated chitosan derivatives enhance fibroblast adhesion and proliferation in wound healing.

Author information

1
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland; West University of Timisoara, Department of Biology-Chemistry, Pestalozzi 16, Timisoara 300115, Romania; West University of Timisoara, Advanced Environmental Research Laboratories, Oituz 4, Timisoara 300086, Romania.
2
University Hospital of Lausanne (CHUV-UNIL), Regenerative Therapy Unit, EPCR/02/ch.Croisettes 22, 1066 Epalinges, Switzerland.
3
West University of Timisoara, Department of Biology-Chemistry, Pestalozzi 16, Timisoara 300115, Romania; West University of Timisoara, Advanced Environmental Research Laboratories, Oituz 4, Timisoara 300086, Romania.
4
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland.
5
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland. Electronic address: Gerrit.Borchard@unige.ch.

Abstract

RGD peptide sequences are known to regulate cellular activities by interacting with α5β1, αvβ5 and αvβ3 integrin, which contributes to the wound healing process. In this study, RGDC peptide was immobilized onto chitosan derivative 1,6-diaminohexane-O-carboxymethyl-N,N,N-trimethyl chitosan (DAH-CMTMC) to display RGDC-promoting adhesion for enhanced wound healing. The efficiency of N-methylation, O-carboxymethylation and spacer grafting was quantitatively and qualitatively analyzed by (1)H NMR and FTIR, yielding 0.38 degree of substitution for N-methylation and >0.85 for O-carboxymethylation. The glass transition temperatures for chitosan derivatives were also studied. Peptide immobilization was achieved through sulfhydryl groups using sulfosuccinimidyl (4-iodoacetyl)amino-benzoate (sulfo-SIAB method). RGDC immobilized peptide onto DAH-CMTMC was found to be about 15.3 μg/mg of chitosan derivative by amino acid analysis (AAA). The significant increase of human dermal fibroblast (HDF) viability in vitro over 7 days suggests that RGDC-functionalized chitosan may lead to enhanced wound healing (viability >140%). Moreover, bio-adhesion and proliferation assays confirmed that coatings of RGDC-functionalized chitosan derivatives exhibit in vitro wound healing properties by enhancing fibroblast proliferation and adhesion. These results showed that RGDC peptide-functionalized chitosan provides an optimal environment for fibroblast adhesion and proliferation.

KEYWORDS:

1,6-Diaminohexane (PubChem CID: 16402); Bioadhesion; Chitosan (PubChem CID: 21896651); Chitosan derivatives; Migration; Proliferation; RGDC peptide; Sulfo-N-succinimidyl (N-Iodoacetyl)aminobenzoate (PubChem CID: 4131104); Wound healing

PMID:
26917381
DOI:
10.1016/j.carbpol.2016.01.045
[Indexed for MEDLINE]

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