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The present study evaluated the tissue response toward a resorbable collagen membrane derived from bovine achilles tendon (test group) in comparison to physiological wound healing (control group). After subcutaneous implantation in Wistar rats over 30 days, histochemical and immunohistochemical methods elucidated the cellular inflammatory response, vascularization pattern, membrane protein and cell absorbance capacity. After 30 days, the test-group induced two different inflammatory patterns. On the membrane surface, multinucleated giant cells (MNGCs) were formed after the accumulation of CD-68-positive cells (macrophages), whereas only mononuclear cells (MNCs) were found within the membrane central region. Peri-implant vascularization was significantly enhanced after the formation of MNGCs. No vessels were found within the central region of the membrane. Physiological wound healing revealed no MNGCs at any time point. These dynamic changes in the cellular reaction and vascularization within the test-group are related typical indications of a foreign body reaction. Due to the membrane-specific porosity, mononuclear cells migrated into the central region, and the membrane maintained its integrity over 30 days by showing no breakdown or disintegration. The ex vivo investigation analyzed the interaction between the membrane and a blood concentrate system, liquid platelet-rich fibrin (liquid PRF), derived from human peripheral blood and consisting of platelets, leukocytes and fibrin. PRF penetrated the membrane after just 15 min. The data question the role of biomaterial-induced MNGCs as a pathological reaction and whether this is acceptable to trigger vascularization or should be considered as an adverse reaction. Therefore, further pre-clinical and clinical studies are needed to identify the types of MNGCs that are induced by clinically approved biomaterials.
The present study aimed to assess the tissue response to the SYMBIOS® resorbable collagen membrane SR, which is derived from bovine Achilles tendon, and compare it to the physiological wound healing of a sham operation as a control.
An ex vivo analysis was performed using injectable platelet-rich fibrin (i-PRF), that is gained by the centrifugation of human venous blood and contains fibrin, leukocytes and platelets, to elucidate the membrane permeability and interactions with human cells and plasma proteins. In the in vivo study, a subcutaneous implantation model was established in Wistar rats to evaluate the cellular reactions for up to 30 days after membrane implantation. Histochemical, immunohistochemical and histomorphometric analyses were performed to assess the cellular inflammatory response, vascularization pattern and cell infiltration capacity.
In the ex vivo study, i-PRF components including fibrin, leukocytes and platelets penetrated the membrane after just 15 minutes. Within the observation period, the cellular reaction in the early phase, which included the first 3 days, produced only mononuclear cells. From 10 to 30 days , the formation of multinucleated giant cells (MNGCs) was induced by the collagen membrane. CD-68 positive cells (macrophages) occurred in a high number on day 3, and the number decreased over time up to day 30. Along with the reduction in the number of CD-68 positive cells, the number of MNGCs increased significantly. The presence of MNGCs was accompanied by significantly increased vascularization within the central region of the membrane, and only mononuclear cells (MNCs) did not produce vascularization. In contrast, the accumulated MNGCs were located on the membrane surface. The control group reflected the physiological process of wound healing, as MNGCs did not form over the 30 day period, and a significantly lower level of vascularization was observed compared with the test group.
This finding showed dynamic changes in the cellular reaction, which indicated a relationship between macrophage fusion and MNGC formation, and vascularization of the collagen membrane is circumstantial evidence of a reaction to a foreign body. However, the collagen membrane was able to maintain its structure and integrity over time, showing no signs of premature breakdown and disintegration due to the specific porosity of its membrane structure.
Therefore, we questioned whether the biomaterial-induced formation of MNGCs should be accepted as a biomaterial-induced cellular reaction that is able to restore vascularization or as an adverse reaction. Therefore, extensive preclinical and clinical studies are needed to investigate the type of MNGCs that form in response to the membrane material studied here.