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In the presented case series for the first time a bilayered, non-crossed-linked collagen matrix has been used in an off-label fashion in order to reconstruct facial skin defects following different types of skin cancer resection. The material is of porcine origin and consists of a spongy and a compact layer. The ratio of the two layers is 1:3 in favour of the spongy layer. The aim of the study was to investigate the potential of this matrix for skin regeneration as an alternative to the standard techniques of skin grafts or flaps. Six patients between 39 and 83\u00a0years old were included in the study based on a therapeutic trial. The collagen matrix was used in seven defects involving the nose, eyelid, forehead- and posterior scalp regions, and ranging from 1,2 to 6\u00a0cm in diameter. Two different head and neck surgeons at two different institutions performed the operations. Each used a different technique in covering the wound following surgery, i.e. with and without a latex-based sheet under the pressure dressing. In three cases cylindrical biopsies were taken after 14\u00a0days. In all cases the biomaterial application was performed without any complication and no adverse effects were observed. Clinically, the collagen matrix contributed to a tension-free skin regeneration, independent of the wound dressing used. The newly regenerated skin showed strong similarity to the adjacent normal tissue both in quality and colour. Histological analysis indicated that the spongy layer replaced the defective connective tissue, by providing stepwise integration into the surrounding implantation bed, while the compact layer was infiltrated by mononuclear cells and contributed to its epithelialization by means of a \u201econductive\u201cprocess from the surrounding epithelial cells. The clinical and histological data demonstrate that the collagen bilayered matrix used in this series contributes to a \u201eGuided-Integrative-Regeneration-Process\u201c, which still needs to be further understood. The biomimetic nature of this material seems to contribute to physiological matrix remodelling, which probably involves other matricellular proteins essential for soft tissue regeneration. A deeper understanding of the mechanism, involved in the tissue integration of this material and its contribution to soft tissue regeneration based on the direct and indirect effect of matricellular proteins could open new therapeutic avenues for biomaterial-based soft tissue regeneration as an alternative to traditional flap-based plastic surgery.<\/jats:p>","DOI":"10.1007\/s12079-015-0313-7","type":"journal-article","created":{"date-parts":[[2015,12,10]],"date-time":"2015-12-10T01:50:29Z","timestamp":1449712229000},"page":"3-15","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Bilayered, non-cross-linked collagen matrix for regeneration of facial defects after skin cancer removal: a new perspective for biomaterial-based tissue reconstruction"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7897-0854","authenticated-orcid":false,"given":"Shahram","family":"Ghanaati","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adorj\u00e1n","family":"Kov\u00e1cs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike","family":"Barbeck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Lorenz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Teiler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nader","family":"Sadeghi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles James","family":"Kirkpatrick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Sader","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,12,9]]},"reference":[{"key":"313_CR1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1146\/annurev.matsci.31.1.81","volume":"31","author":"JM Anderson","year":"2001","unstructured":"Anderson JM (2001) Biological responses to materials. 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