title: A pre-clinical functional assessment of an acellular scaffold intended for the treatment of hard-to-heal wounds.
abstract: The majority of the population experience successful wound-healing outcomes; however, 1-3% of those aged over 65 years experience delayed wound healing and wound perpetuation. These hard-to-heal wounds contain degraded and dysfunctional extracellular matrix (ECM); yet, the integrity of this structure is critical in the processes of normal wound healing. Here, we evaluated a novel synthetic matrix protein for its ability to act as an acellular scaffold that could replace dysfunctional ECM. In this regard, the synthetic protein was subjected to adsorption and diffusion assays using collagen and human dermal tissues; evaluated for its ability to influence keratinocyte and fibroblast attachment, migration and proliferation and assessed for its ability to influence in vivo wound healing in a porcine model. Critically, these experiments demonstrate that the matrix protein adsorbed to collagen and human dermal tissue but did not diffuse through human dermal tissue within a 24-hour observation period, and facilitated cell attachment, migration and proliferation. In a porcine wound-healing model, significantly smaller wound areas were observed in the test group compared with the control group following the third treatment. These data provide evidence that the synthetic matrix protein has the ability to function as an acellular scaffold for wound-healing purposes.
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD,, Australia.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Shooter
authors.forename: Derek R
authors.initials: DR
authors.lastname: Van Lonkhuyzen
authors.forename: Tristan I
authors.initials: TI
authors.lastname: Croll
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.forename: James A
authors.initials: JA
authors.lastname: Broadbent
authors.forename: Dario
authors.initials: D
authors.lastname: Stupar
authors.forename: Emily C
authors.initials: EC
authors.lastname: Lynam
authors.forename: Zee
authors.initials: Z
authors.lastname: Upton
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D020405:Dermis / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D013552:Swine; D054457:Tissue Scaffolds; D019096:Vitronectin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014945:Wound Healing; D014950:Wounds, Penetrating / Q000628:therapy*
chemical_list: D019096:Vitronectin
keywords: Acellular scaffold; Extracellular matrix; Hard-to-heal wounds
references.citation: Int J Biochem Cell Biol. 1999 May;31(5):539-44
references.pmid: 10399314
references.citation: Curr Probl Dermatol. 1978;7:39-52
references.pmid: 752456
references.citation: Pharm Res. 1987 Aug;4(4):337-41
references.pmid: 3509887
references.citation: Surgery. 2000 Jun;127(6):696-704
references.pmid: 10840366
references.citation: Int Wound J. 2010 Jun;7(3):125-6
references.pmid: 20602642
references.citation: Tissue Eng Part C Methods. 2010 Oct;16(5):1111-23
references.pmid: 20109066
references.citation: J Invest Dermatol. 1975 Mar;64(3):190-5
references.pmid: 123263
references.citation: Cell Struct Funct. 1988 Jun;13(3):217-25
references.pmid: 2458194
references.citation: Wound Repair Regen. 2006 May-Jun;14(3):252-8
references.pmid: 16808803
references.citation: Ostomy Wound Manage. 1994 Sep;40(7):50-2, 54, 56-60
references.pmid: 7546091
references.citation: Wound Repair Regen. 2001 Mar-Apr;9(2):66-76
references.pmid: 11350644
references.citation: Exp Dermatol. 1993 Feb;2(1):29-37
references.pmid: 8156167
references.citation: Wound Repair Regen. 2006 May-Jun;14(3):240-6
references.pmid: 16808801
references.citation: Acta Derm Venereol. 2000 May;80(3):179-84
references.pmid: 10954207
references.citation: J Invest Dermatol. 1992 Apr;98(4):410-6
references.pmid: 1372338
references.citation: Int J Low Extrem Wounds. 2009 Mar;8(1):19-27
references.pmid: 19164416
references.citation: J Invest Dermatol. 1996 Feb;106(2):335-41
references.pmid: 8601737
references.citation: Arch Dermatol Res. 1998 Sep;290(9):490-6
references.pmid: 9808342
references.citation: Am J Clin Dermatol. 2007;8(2):61-6
references.pmid: 17428110
references.citation: J Anat. 1997 May;190 ( Pt 4):601-11
references.pmid: 9183682
references.citation: Nurs Times. 2008 Jan 22-28;104(3):44-5
references.pmid: 18293879
references.citation: Br J Dermatol. 2001 Feb;144(2):254-9
references.pmid: 11251555
references.citation: Am J Pathol. 1984 Dec;117(3):349-54
references.pmid: 6507585