title: Bioactive bilayered dressing for compromised epidermal tissue regeneration with sequential activity of complementary agents.
abstract: The article deals with the design, preparation, and evaluation of a new bilayered dressing for application in the healing of compromised wounds. The system is based on the sequential release of two complementary bioactive components to enhance the activation of the regeneration of dermal tissue. The internal layer is a highly hydrophilic and biodegradable film of gelatin and hyaluronic acid (HG), crosslinked with the natural compound genipin, which reacts with the amine groups of gelatin. This film is loaded with the proangiogenic, anti-inflammatory, and antibacterial peptide, proadrenomedullin N-terminal 20 peptide (PAMP), that is released slowly in the wound site. The external layer, more stable and less hydrophilic, is constituted by a biodegradable polyurethane derived from poly(caprolactone) and pluronic L61. This layer is loaded with resorbable nanoparticles of bemiparin (a fractionated low molecular weight heparin), which promotes the activation of growth factors, FGF and VEGF, and provides a good biomechanical stability and controlled permeability of the bilayered dressing. Experiments carried out in mice demonstrate the excellent angiogenic effect of the HG film in the dermal tissue. Application of the bilayered dressing in the wound healing rabbit ear model shows an improved cicatrization of the wound in both ischemic and non-ischemic defects, favoring epithelialization and reducing noticeably the contraction and the inflammation.
authors.affiliation: Biomaterials Group, Institute of Polymer Science and Technology (ICTP-CSIC), Madrid, Spain; Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Felisa
authors.initials: F
authors.lastname: Reyes-Ortega
authors.affiliation: Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Department of Medical Specialities, School of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cifuentes
authors.affiliation: Biomaterials Group, Institute of Polymer Science and Technology (ICTP-CSIC), Madrid, Spain; Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain. Electronic address: gema@ictp.csic.es.
authors.forename: Gema
authors.initials: G
authors.lastname: Rodríguez
authors.affiliation: Biomaterials Group, Institute of Polymer Science and Technology (ICTP-CSIC), Madrid, Spain; Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Aguilar
authors.affiliation: Biomaterials Group, Institute of Polymer Science and Technology (ICTP-CSIC), Madrid, Spain; Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: González-Gómez
authors.affiliation: Biomaterials Group, Institute of Polymer Science and Technology (ICTP-CSIC), Madrid, Spain.
authors.forename: Raul
authors.initials: R
authors.lastname: Solis
authors.affiliation: Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Department of Medical Specialities, School of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: Natalio
authors.initials: N
authors.lastname: García-Honduvilla
authors.affiliation: Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Department of Medical Specialities, School of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Buján
authors.affiliation: Angiogenesis Study Group, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
authors.forename: Josune
authors.initials: J
authors.lastname: García-Sanmartin
authors.affiliation: Angiogenesis Study Group, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Martínez
authors.affiliation: Biomaterials Group, Institute of Polymer Science and Technology (ICTP-CSIC), Madrid, Spain; Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Julio San
authors.initials: JS
authors.lastname: Román
mesh_terms: D020341:Absorbable Implants; D053607:Adrenomedullin / Q000008:administration & dosage*; D000818:Animals; D001458:Bandages; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis; D004338:Drug Combinations; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D012867:Skin / Q000187:drug effects / Q000254:growth & development* / Q000293:injuries*; D057968:Transdermal Patch; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D006495:Heparin, Low-Molecular-Weight; D053607:Adrenomedullin; C411345:bemiparin
keywords: Heparin; Hydrogel; Nanoparticle; Polyurethane; Wound dressing