title: Dermal regeneration in full-thickness wounds in Yucatan miniature pigs using a biodegradable copolymer.
abstract: The aim of this study was to assess the performance of a biodegradable dermal substrate in deep dermal skin defects. The substrate consisted of a synthetic biodegradable matrix called Polyactive, which is an elastomeric poly (ether)/ poly (ester) block copolymer. This matrix was manufactured either as a porous substrate, with gradually changing pore size (BISKIN-M), or as a bilayer consisting of a porous underlayer with a fully dense surface layer (BISKIN). Cell-free matrices and matrices seeded with autologous or allogeneic porcine fibroblasts were applied to full-thickness skin wounds in Yucatan miniature pigs. Biopsies were taken at different time intervals up to 24-months post-transplantation. Although all BISKIN substrates showed little or no adherence to the wound bed, the adherence of the BISKIN-M substrates to the underlying wound was achieved within minutes after application. Therefore, only BISKIN-M Polyactive substrates were further evaluated. Wound contraction was inhibited by both cell-free and fibroblast-populated substrates. All substrates showed extensive neovascular and fibrous tissue ingrowth within 2-weeks post-transplantation. Furthermore, during this time period, matrix degradation was observed, starting with the fragmentation of the polymers into particles, which were phagocytized by macrophages. These processes occurred actively up to 3 months and ceased thereafter. Cell-free substrates degraded faster, and also, the collagen deposition was lower as compared with cell-seeded substrates. The tissue surrounding the remnants of the Polyactive substrates after 24-months post-transplantation consisted of a mature connective tissue. The newly formed collagen had the same distribution pattern as observed in normal native dermis. We conclude therefore that treatment of full-thickness skin defects with fibroblast-populated BISKIN-M Polyactive substrates leads to satisfactory dermal regeneration.
authors.affiliation: Department of Dermatology, Biomaterials Research Group, Leiden University Medical Center, The Netherlands.
authors.forename: A G
authors.initials: AG
authors.lastname: Van Dorp
authors.forename: M C
authors.initials: MC
authors.lastname: Verhoeven
authors.forename: H K
authors.initials: HK
authors.lastname: Koerten
authors.forename: T H
authors.initials: TH
authors.lastname: Van Der Nat-Van Der Meij
authors.forename: C A
authors.initials: CA
authors.lastname: Van Blitterswijk
authors.forename: M
authors.initials: M
authors.lastname: Ponec
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001706:Biopsy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000637:transplantation*; D011091:Polyesters / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016062:Porosity; D012879:Skin Physiological Phenomena; D017768:Skin, Artificial; D013552:Swine; D013556:Swine, Miniature; D014945:Wound Healing / Q000502:physiology*
chemical_list: D011091:Polyesters; C072932:polyethylene oxide-polybutylene terephthalate copolymer; C041733:poly(1,4-butylene terephthalate); D011092:Polyethylene Glycols