title: Study of stiffness effects of poly(amidoamine)-poly(n-isopropyl acrylamide) hydrogel on wound healing.
abstract: The mechanical miss-match between the host and an implanted foreign body is one of the primary causes for implantation failure. To enhance the efficacy in wound repair, we developed stiffness-tunable temperature-sensitive hydrogels composed of poly(amidoamine) (PAA)-based poly(n-isopropyl acrylamide) (PNIPAM). PNIPAM-PAA hydrogels with three different stiffness fabricated by varying the concentrations of poly(amidoamine) were chosen for morphology and rheology tests. The degradation rate and cell compatibility of gels were also characterized. The PAA-PNIPAM hydrogels were then tested in a wound healing model of mice with full-thickness skin loss. We found that the stiffness of hydrogels has an impact on the wound healing process mainly by regulating the cell activities in the proliferation phase. PNIPAM-PAA hydrogels with appropriate stiffness reduce scar formation and improve wound healing by promoting myofibroblast transformation, keratinocytes proliferation, extracellular matrix synthesis and remodeling. Moreover, the stiffness of hydrogels impact on the secretion of TGF-β1 and bFGF, which play an important role in skin wound healing. These results suggest that the therapeutic effects of hydrogels in skin wound healing can by regulated by hydrogels' stiffness.
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Departments of Mechanical Engineering, Biochemistry and Medical Genetics, University of Manitoba, and Manitoba Institute of Child Health, Winnipeg, MB R3T 2N2, Canada.
authors.forename: Shixuan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Departments of Mechanical Engineering, Biochemistry and Medical Genetics, University of Manitoba, and Manitoba Institute of Child Health, Winnipeg, MB R3T 2N2, Canada.
authors.forename: Junbin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jianyang
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Biosystem Engineering, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China. Electronic address: zlulu70@126.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Departments of Mechanical Engineering, Biochemistry and Medical Genetics, University of Manitoba, and Manitoba Institute of Child Health, Winnipeg, MB R3T 2N2, Canada. Electronic address: malcolm.xing@umanitoba.ca.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Xing
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou 510515, China. Electronic address: zlilyzh@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D004548:Elasticity; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D055595:Mechanical Phenomena; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D011073:Polyamines / Q000737:chemistry*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000178:Acrylamides; D001672:Biocompatible Materials; D024042:Collagen Type I; D020100:Hydrogels; C531249:Poly(amidoamine); D011073:Polyamines; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; C067295:N-isopropylacrylamide
keywords: Hydrogel; P(N-isopropylacrylamide); Poly(amidoamine); Skin wound healing; Stiffness