{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:12:41Z","timestamp":1767625961913,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"International Atomic Energy Agency","award":["18202 (CRP F23030)","UIDB\/04349\/2020+UIDP\/04349\/2020","UIDB\/00100\/2020","UIDB\/00329\/2020"],"award-info":[{"award-number":["18202 (CRP F23030)","UIDB\/04349\/2020+UIDP\/04349\/2020","UIDB\/00100\/2020","UIDB\/00329\/2020"]}]},{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia I.P.","award":["18202 (CRP F23030)","UIDB\/04349\/2020+UIDP\/04349\/2020","UIDB\/00100\/2020","UIDB\/00329\/2020"],"award-info":[{"award-number":["18202 (CRP F23030)","UIDB\/04349\/2020+UIDP\/04349\/2020","UIDB\/00100\/2020","UIDB\/00329\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Frequently, deep partial and full-thickness skin wounds do not spontaneously regenerate. To restore the normal function of skin, epidermal and dermal components have to be supplied to the wound bed by grafting various substrates. Available options are limited and frequently costly. Herein, authors present a possible approach using 3D skin scaffolds capable of mimicking structure and biological functions of the extracellular matrix, providing, in parallel, a good environment for cell attachment, proliferation and differentiation. Low-molecular weight chitosan-based membranes were prepared by freeze-drying and ionizing radiation techniques to be used as skin scaffolds. Poly (vinyl alcohol), PVA, vinyl pyrrolidone, VP, and gelatin from cold water fish were incorporated. Information regarding membranes\u2019 physical-chemical properties from SEM analysis, swelling and weight loss, together with biological response through in vitro assays (using Human Caucasian Fetal Foreskin Fibroblast) allowed the selection of an optimized batch of membranes that was used as skin scaffold in a dorsal rat model wound. The in vivo implantation assays (in Wistar rats) resulted in very promising results: (i) healing process faster than control; (ii) good vascularization; (iii) viable new tissues morphologically functional.<\/jats:p>","DOI":"10.3390\/pharmaceutics14122736","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T05:50:52Z","timestamp":1670392252000},"page":"2736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Chitosan-Based Membranes for Skin Wound Repair in a Dorsal Fold Chamber Rat Model"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0893-0686","authenticated-orcid":false,"given":"Maria Helena","family":"Casimiro","sequence":"first","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico (IST), Universidade de Lisboa, 2695-066 Bobadela, Portugal"}]},{"given":"Lu\u00eds M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico (IST), Universidade de Lisboa, 2695-066 Bobadela, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico (IST), Universidade de Lisboa, 2695-066 Bobadela, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-0098","authenticated-orcid":false,"given":"Pedro M. P.","family":"Santos","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico (IST), Universidade de Lisboa, 2695-066 Bobadela, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1235-0107","authenticated-orcid":false,"given":"Jo\u00e3o P.","family":"Leal","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico (IST), Universidade de Lisboa, 2695-066 Bobadela, Portugal"},{"name":"Centro de Qu\u00edmica Estrutural (CQE), Instituto Superior T\u00e9cnico (IST), Universidade de Lisboa, 2695-066 Bobadela, Portugal"}]},{"given":"Gabriela","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Centro de Ecologia, Evolu\u00e7\u00e3o e Altera\u00e7\u00f5es Ambientais (cE3c) & CHANGE\u2014Global Change and Sustainability Institute, Departamento de Biologia Animal, Faculdade de Ci\u00eancias, Universidade de Lisboa (FCUL), 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3661-3760","authenticated-orcid":false,"given":"In\u00eas","family":"Iria","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"given":"Sara","family":"Alves","sequence":"additional","affiliation":[{"name":"Departamento de Anatomia, NOVA Medical School|Faculdade de Ci\u00eancias M\u00e9dicas (NMS|FCM), Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9837-0197","authenticated-orcid":false,"given":"Diogo","family":"Pais","sequence":"additional","affiliation":[{"name":"Departamento de Anatomia, NOVA Medical School|Faculdade de Ci\u00eancias M\u00e9dicas (NMS|FCM), Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5537-9340","authenticated-orcid":false,"given":"Diogo","family":"Casal","sequence":"additional","affiliation":[{"name":"Centro de Estudos de Doen\u00e7as Cr\u00f3nicas (CEDOC), NOVA Medical School|Faculdade de Ci\u00eancias M\u00e9dicas (NMS|FCM), Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1801471","DOI":"10.1002\/adhm.201801471","article-title":"Current and Future Perspectives on Skin Tissue Engineering: Key Features of Biomedical Research, Translational Assessment, and Clinical Application","volume":"8","author":"Yu","year":"2019","journal-title":"Adv. Healthc. Mater."},{"key":"ref_2","first-page":"1","article-title":"Skin Tissue Engineering: Principles and Advances","volume":"1","author":"Dhasmana","year":"2018","journal-title":"J. Dermatol. Ski. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fbioe.2018.00086","article-title":"Skin Tissue Substitutes and Biomaterial Risk Assessment and Testing","volume":"6","author":"Savoji","year":"2018","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s00266-017-1069-7","article-title":"A New Human-Derived Acellular Dermal Matrix for Breast Reconstruction Available for the European Market: Preliminary Results","volume":"42","author":"Folli","year":"2018","journal-title":"Aesthetic Plast. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"244","DOI":"10.5152\/ejbh.2020.5848","article-title":"A Picture of Breast Reconstruction in a Public Oncology Hospital in Latin America: A Ten-Year Experience","volume":"16","author":"Groth","year":"2020","journal-title":"Eur. J. Breast Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/iwj.12126","article-title":"Development and ultra-structure of an ultra-thin silicone epidermis of bioengineered alternative tissue","volume":"12","author":"Wessels","year":"2013","journal-title":"Int. Wound J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s10353-022-00757-9","article-title":"Skin regeneration, repair, and reconstruction: Present and future","volume":"54","author":"Kamolz","year":"2022","journal-title":"Eur. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40902-022-00344-8","article-title":"Prevalence of complications associated with polymer-based alloplastic materials in nasal dorsal augmentation: A systematic review and meta-analysis","volume":"44","author":"Keyhan","year":"2022","journal-title":"Maxillofac. Plast. Reconstr. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e4466","DOI":"10.1097\/GOX.0000000000004466","article-title":"Current Concepts in Cranial Reconstruction: Review of Alloplastic Materials","volume":"10","author":"Johnston","year":"2022","journal-title":"Plast. Reconstr. Surg.-Glob. Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/00006534-200107000-00014","article-title":"Staged Reconstruction after Gunshot Wounds to the Abdomen","volume":"108","author":"Cohen","year":"2001","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_11","first-page":"4","article-title":"Skin Substitutes: A Brief Review of Types and Clinical Applications","volume":"24","author":"Alrubaiy","year":"2009","journal-title":"Oman. Med. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.jamcollsurg.2013.03.027","article-title":"Tissue Engineering of Skin","volume":"217","author":"Kamel","year":"2013","journal-title":"J. Am. Coll. Surg."},{"key":"ref_13","first-page":"27","article-title":"Chitosan Based Scaffolds and Their Applications in Wound Healing","volume":"10","author":"Ahmed","year":"2016","journal-title":"Achiev. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jare.2017.01.005","article-title":"A review on polymeric hydrogel membranes for wound dressing applications: PVA-based hydrogel dressings","volume":"8","author":"Kamoun","year":"2017","journal-title":"J. Adv. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7564","DOI":"10.1016\/j.biomaterials.2005.05.050","article-title":"A three-layered nano-carbonated hydroxyapatite\/collagen\/PLGA composite membrane for guided tissue regeneration","volume":"26","author":"Liao","year":"2005","journal-title":"Biomaterials"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"012072","DOI":"10.1088\/1742-6596\/1347\/1\/012072","article-title":"Modification of non-woven materials based on sodium alginate for tissue-engineering","volume":"1347","author":"Tenchurin","year":"2019","journal-title":"J. Physics Conf. Ser."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1369-7021(11)70058-X","article-title":"Biomaterials & scaffolds for tissue engineering","volume":"14","year":"2011","journal-title":"Mater. Today"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.1016\/j.biomaterials.2006.06.028","article-title":"Freeze casting of hydroxyapatite scaffolds for bone tissue engineering","volume":"27","author":"Deville","year":"2006","journal-title":"Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.msec.2014.10.051","article-title":"In vitro and in vivo evaluation of electrospun nanofibers of PCL, chitosan and gelatin: A comparative study","volume":"46","author":"Gomes","year":"2015","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/wnan.55","article-title":"Nanotechnology in the design of soft tissue scaffolds: Innovations in structure and function","volume":"2","author":"Ayres","year":"2009","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1016\/j.biomaterials.2005.05.078","article-title":"Towards a methodology for the effective surface modification of porous polymer scaffolds","volume":"26","author":"Safinia","year":"2005","journal-title":"Biomaterials"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Casimiro, M.H., Pereira, A., Leal, J.P., Rodrigues, G., and Ferreira, L.M. (2021). Chitosan\/PVA Based Membranes Processed by Gamma Radiation as Scaffolding Materials for Skin Regeneration. Membranes, 11.","DOI":"10.3390\/membranes11080561"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Casimiro, M.H., Gomes, S.R., Rodrigues, G., Leal, J.P., and Ferreira, L.M. (2018). Chitosan\/Poly(vinylpyrrolidone) Matrices Obtained by Gamma-Irradiation for Skin Scaffolds: Characterization and Preliminary Cell Response Studies. Materials, 11.","DOI":"10.3390\/ma11122535"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s41061-016-0092-5","article-title":"Chitosan-Based Matrices Prepared by Gamma Irradiation for Tissue Regeneration: Structural Properties vs. Preparation Method","volume":"375","author":"Casimiro","year":"2016","journal-title":"Top. Curr. Chem."},{"key":"ref_25","unstructured":"Cabo Verde, S., Nunes, I., Dores, V., Melo, R., Oliveira, S., and Botelho, M.L. (2010). Establishment of Sterilization Doses for Biomaterial Products. Isotope Technologies and Applications\u2013New Horizons, Proceedings of the NAARRI International Conference, Mumbai, India, 13\u201315 December 2010, NAARRI."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"355","DOI":"10.4329\/wjr.v8.i4.355","article-title":"Radiation sterilization of tissue allografts: A review","volume":"8","author":"Singh","year":"2016","journal-title":"World J. Radiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ijpharm.2010.05.034","article-title":"Suitability of gamma irradiated chitosan based membranes as matrix in drug release system","volume":"395","author":"Casimiro","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.radphyschem.2004.05.040","article-title":"Radiation technologies: Past, present and future","volume":"71","author":"Chmielewski","year":"2004","journal-title":"Radiat. Phys. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"216","DOI":"10.22203\/eCM.v032a14","article-title":"Lumbar intervertebral disc allograft transplantation: Healing and remodelling of the bony structure","volume":"32","author":"Huang","year":"2016","journal-title":"Eur. Cell. Mater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/srt.12776","article-title":"A simple morphometric analysis method for dermal microstructure using color thresholding and moments","volume":"26","author":"Hong","year":"2019","journal-title":"Ski. Res. Technol."},{"key":"ref_31","first-page":"1","article-title":"Dorsal skinfold chamber models in mice","volume":"6","author":"Schreiter","year":"2017","journal-title":"GMS Interdiscip. Plast. Reconstr. Surg. DGPW"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s10616-015-9895-4","article-title":"Scaffolds and cells for tissue regeneration: Different scaffold pore sizes\u2014Different cell effects","volume":"68","author":"Bagdonas","year":"2016","journal-title":"Cytotechnology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14","DOI":"10.5604\/01.3001.0014.6174","article-title":"The suitability of scanning electron microscopy in the evaluation of bone structure surfaces and selection of alloplastic materials for facial skeletal reconstruction","volume":"75","author":"Job","year":"2020","journal-title":"Otolaryngol. Polska"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/pat.1558","article-title":"Synthesis, characterization, and swelling behaviors of chitosan-g-poly(acrylic acid)\/poly(vinyl alcohol) semi-IPN superabsorbent hydrogels","volume":"22","author":"Liu","year":"2011","journal-title":"Polym. Adv. Technol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Silvestro, I., Francolini, I., Di Lisio, V., Martinelli, A., Pietrelli, L., D\u2019Abusco, A.S., Scoppio, A., and Piozzi, A. (2020). Preparation and Characterization of TPP-Chitosan Crosslinked Scaffolds for Tissue Engineering. Materials, 13.","DOI":"10.3390\/ma13163577"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1002\/app.10812","article-title":"Preparation and properties of PVA\/PVP hydrogels containing chitosan by radiation","volume":"85","author":"Nho","year":"2002","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"202","DOI":"10.22203\/eCM.v032a13","article-title":"The dorsal skinfold chamber: A versatile tool for preclinical research in tissue engineering and regenerative medicine","volume":"32","author":"Laschke","year":"2016","journal-title":"Eur. Cell. Mater."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/12\/2736\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:35:44Z","timestamp":1760146544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/12\/2736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,7]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["pharmaceutics14122736"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14122736","relation":{},"ISSN":["1999-4923"],"issn-type":[{"type":"electronic","value":"1999-4923"}],"subject":[],"published":{"date-parts":[[2022,12,7]]}}}