title: Peptide-decorated chitosan derivatives enhance fibroblast adhesion and proliferation in wound healing.
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.
authors.affiliation: 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.
authors.forename: V
authors.initials: V
authors.lastname: Patrulea
authors.affiliation: University Hospital of Lausanne (CHUV-UNIL), Regenerative Therapy Unit, EPCR/02/ch.Croisettes 22, 1066 Epalinges, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Hirt-Burri
authors.affiliation: University Hospital of Lausanne (CHUV-UNIL), Regenerative Therapy Unit, EPCR/02/ch.Croisettes 22, 1066 Epalinges, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Jeannerat
authors.affiliation: University Hospital of Lausanne (CHUV-UNIL), Regenerative Therapy Unit, EPCR/02/ch.Croisettes 22, 1066 Epalinges, Switzerland.
authors.forename: L A
authors.initials: LA
authors.lastname: Applegate
authors.affiliation: 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.
authors.forename: V
authors.initials: V
authors.lastname: Ostafe
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Jordan
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland. Electronic address: Gerrit.Borchard@unige.ch.
authors.forename: G
authors.initials: G
authors.lastname: Borchard
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C118071:N-trimethyl chitosan chloride; D009842:Oligopeptides; C568214:arginyl-glycyl-aspartyl-cysteine; D048271:Chitosan
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