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“Covering skin defects with a xenogeneic collagen matrix in comparison with a skin graft - A multicenter randomized controlled trial”

Kai Wermker, Max Hogrebe, Nils-Claudius Gellrich, Anja Heselich, Shahram Ghanaati

Journal of Cranio-Maxillo-Facial Surgery vol.52,1(2024):101–107. doi:10.1016/j.jcms.2023.10.009.


The objective of this study was to analyze, in a randomized controlled multicenter trial, whether a xenogeneic collagen matrix (XCM) could be used to cover skin defects. Patients with the need for skin excisions were recruited and randomized to treatment with a skin graft after a period of granulation or to treatment with an XCM. The results were evaluated by two independent observers on the Patient and Observer Scar Assessment Scale. On this scale, scars are ranked from 1 to 10 in six different categories. Results range from 6 to 60, with lower scores representing scars closer to normal skin. The results 6 months after reconstruction were used as primary endpoint and compared in a non-inferiority approach. A total of 39 wounds in the head and neck region were analyzed. The mean results were 16.55 (standard deviation 6.8) for XCM and 16.83 (standard deviation 8.21) in the control group. The result of the XCM was not significantly inferior to the result of the skin graft (p = 0.91). Within the limitations of the study, it seems that the use of xenogeneic collagen matrices is a viable alternative to other approaches in small skin defects, and therefore should be taken into account whenever the reduction of patient morbidity to a minimum is the priority.

Covering skin defects with a xenogeneic collagen matrix in comparison with a skin graft – A multicenter randomized controlled trial - ScienceDirect

“Bilayered, non-cross-linked collagen matrix for regeneration of facial defects after skin cancer removal: a new perspective for biomaterial-based tissue reconstruction”

Shahram Ghanaati, Adorján Kovács, Mike Barbeck, Jonas Lorenz, Anna Teiler, Nader Sadeghi, Charles James Kirkpatrick, Robert Sader

Journal of Cell Communication and Signaling. 2016 Mar;10(1):3-15. doi: 10.1007/s12079-015-0313-7. Epub 2015 Dec 9.


Classically skin defects are covered by split thickness skin grafts or by means of local or regional skin flaps. 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 years 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 cm 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 days. 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 "conductive" process from the surrounding epithelial cells. The clinical and histological data demonstrate that the collagen bilayered matrix used in this series contributes to a "Guided-Integrative-Regeneration-Process", 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.

Bilayered, non-cross-linked collagen matrix for regeneration of facial defects after skin cancer removal: a new perspective for biomaterial-based tissue reconstruction - PubMed (nih.gov)

“Plastic Coverage of a Lentigo-Maligna Defect in the Cheek, an Alternative Practice Concept.”

Andreas Born, Hans-Ulrich Markmann

London Journal of Medical and Health Research vol 24, 1 (2024)


We have already presented our concept to close more extensive defects after tumor resection of basal cell carcinoma in the head and neck region in scientific journals [1, 2]. Essentially, the procedure consists of suturing a defect wound by approximation with an overlocking hem suture. over a period of about 3 months. The granulating wound is additionally covered by a collagen membrane and protected with a custom-made, stitched-on dressing plate. It seems to us to be logical to do this also for resection defects of other resection defects of other entities.

Plastic-Coverage-of-a-Lentigo-Maligna-Defect-in-the-Cheek-an-Alternative-Practice-Concept.pdf (journalspress.com)

“Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic.”

Shahram Ghanaati, Markus Schlee, Matthew J Webber, Ines Willershausen, Mike Barbeck, Ela Balic, Christoph Görlach, Samuel I Stupp, Robert A Sader, C James Kirkpatrick

Biomedical materials vol.6,1(2011): 015010. doi:10.1088/1748–6041/6/1/015010.


This study evaluates a new collagen matrix that is designed with a bilayered structure in order to promote guided tissue regeneration and integration within the host tissue. This material induced a mild tissue reaction when assessed in a murine model and was well integrated within the host tissue, persisting in the implantation bed throughout the in vivo study. A more porous layer was rapidly infiltrated by host mesenchymal cells, while a layer designed to be a barrier allowed cell attachment and host tissue integration, but at the same time remained impermeable to invading cells for the first 30 days of the study. The tissue reaction was favorable, and unlike a typical foreign body response, did not include the presence of multinucleated giant cells, lymphocytes, or granulation tissue. In the context of translation, we show preliminary results from the clinical use of this biomaterial applied to soft tissue regeneration in the treatment of gingival tissue recession and exposed roots of human teeth. Such a condition would greatly benefit from guided tissue regeneration strategies. Our findings demonstrate that this material successfully promoted the ingrowth of gingival tissue and reversed gingival tissue recession. Of particular importance is the fact that the histological evidence from these human studies corroborates our findings in the murine model, with the barrier layer preventing unspecific tissue ingrowth, as the scaffold becomes infiltrated by mesenchymal cells from adjacent tissue into the porous layer. Also in the clinical situation no multinucleated giant cells, no granulation tissue and no evidence of a marked inflammatory response were observed. In conclusion, this bilayered matrix elicits a favorable tissue reaction, demonstrates potential as a barrier for preferential tissue ingrowth, and achieves a desirable therapeutic result when applied in humans for soft tissue regeneration.

Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic - PubMed (nih.gov)


“Biologization of Collagen-Based Biomaterials Using Liquid-Platelet-Rich Fibrin: New Insights into Clinically Applicable Tissue Engineering.”

Sarah Al-Maawi, Carlos Herrera-Vizcaíno, Anna Orlowska, Ines Willershausen, Robert Sader, Richard J Miron, Joseph Choukroun, Shahram Ghanaati

Materials vol.12,23 3993. 2 Dec.2019, doi:10.3390/ma12233993.


Platelet-rich fibrin (PRF) is a blood concentrate derived from venous blood that is processed without anticoagulants by a one-step centrifugation process. This three-dimensional scaffold contains inflammatory cells and plasma proteins entrapped in a fibrin matrix. Liquid-PRF was developed based on the previously described low-speed centrifuge concept (LSCC), which allowed the introduction of a liquid-PRF formulation of fibrinogen and thrombin prior to its conversion to fibrin. Liquid-PRF was introduced to meet the clinical demand for combination with biomaterials in a clinically applicable and easy-to-use way. The aim of the present study was to evaluate, ex vivo, the interaction of the liquid-PRF constituents with five different collagen biomaterials by histological analyses. The results first demonstrated that large variability existed between the biomaterials investigated. Liquid-PRF was able to completely invade Mucograft® (MG; Geistlich Biomaterials, Wolhusen, Switzerland) and to partly invade Bio-Gide® (BG; Geistlich Biomaterials, Wolhusen, Switzerland) and Mucoderm® (MD; Botiss Biomaterials, Berlin, Germany), and Collprotect® (CP; Botiss Biomaterials, Berlin, Germany) showed only a superficial interaction. The BEGO® collagen membrane (BCM; BEGO Implant Systems) appeared to be completely free of liquid-PRF. These results were confirmed by the different cellular penetration and liquid-PRF absorption coefficient (PAC) values of the evaluated membranes. The present study demonstrates a system for loading biomaterials with a complex autologous cell system (liquid-PRF) in a relatively short period of time and in a clinically relevant manner. The combination of biomaterials with liquid-PRF may be clinically utilized to enhance the bioactivity of collagen-based biomaterials and may act as a biomaterial-based growth factor delivery system.

Biologization of Collagen-Based Biomaterials Using Liquid-Platelet-Rich Fibrin: New Insights into Clinically Applicable Tissue Engineering - PubMed (nih.gov)

“The Biomaterial-Induced Cellular Reaction Allows a Novel Classification System Regardless of the Biomaterials Origin.”

Sarah Al-Maawi, James L Rutkowski, Robert Sader, C James Kirkpatrick, Shahram Ghanaati

The Journal of oral implantology vol.46,3 (2020): 190–207. doi:10.1563/aaid-joi-D-19-00201.


Several different biomaterials are being introduced for clinical applications. However, no current material-specific systematic studies define parameters for evaluating these materials. The aim of this retrospective animal study is to classify biomaterials according to the in vivo induced cellular reaction and outline the clinical consequence of the biomaterial-specific cellular reaction for the regeneration process. A retrospective histologic analysis was performed for 13 polymeric biomaterials and 19 bone substitute materials (BSMs) (of various compositions and origins) that were previously implanted in a standardized subcutaneous model. Semiquantitative analyses were performed at days 3, 15, and 30 after implantation according to a standardized score for the induction of multinucleated giant cells (MNGCs) and vascularization rate. The induced cellular reaction in response to different polymeric materials allowed their classification according to the MNGC score in the following groups: class I induced no MNGCs at any time point, class II induced and maintained a constant number of MNGCs over 30 days, and class III induced MNGCs and provided an increasing number over 30 days. All BSMs induced MNGCs to varying extents. Therefore, the resultant BSM classifications are as follows: class I induced MNGCs with a decreasing number, class II induced and maintained constant MNGCs over 30 days, and class III induced MNGCs with increasing number over 30 days. These observations were mostly related to the biomaterial physicochemical properties and were independent of the biomaterial origin. Consequently, the induction of MNGCs and their increase over 30 days resulted in disintegration of the biomaterial. By contrast, the absence of MNGCs resulted in an integration of the biomaterial within the host tissue. This novel classification provides clinicians a tool to assess the capacity and suitability of biomaterials in the intended clinical indication for bone and soft tissue implantations.

The Biomaterial-Induced Cellular Reaction Allows a Novel Classification System Regardless of the Biomaterials Origin - PubMed (nih.gov)