RESUMEN
GBR (guided bone regeneration) is a standard procedure for building up bony defects in the jaw. In this procedure, resorbable membranes made of bovine and porcine collagen are increasingly being used, which, in addition to many possible advantages, could have the potential disadvantage of a shorter barrier functionality, especially when augmenting large-volume defects. Thus, it is of importance to evaluate the integration behavior and especially the standing time of barrier membranes using specialized methods to predict its respective biocompatibility. This study is intended to establish a new histomorphometrical analysis method to quantify the integration rate of collagen-based barrier membranes. Three commercially available barrier membranes, i.e., non-crosslinked membranes (BioGide® and Jason® membrane), a ribose-crosslinked membrane (Ossix® Plus), and a newly developed collagen-hyaluronic acid-based (Coll-HA) barrier membrane were implanted in the subcutaneous tissue of 48 6-8-week-old Wistar rats. The explants, after three timepoints (10, 30, and 60 days), were processed and prepared into histological sections for histopathological (host tissue response) and histomorphometrical (cellular invasion) analyses. 10 days after implantation, fragmentation was not evident in any of the study groups. The sections of the Coll-HA, Jason® and BioGide® membranes showed a similar mild inflammatory reaction within the surrounding tissue and an initial superficial cell immigration. Only in the Ossix® Plus group very little inflammation and no cell invasion was detected. While the results of the three commercially available membranes remained intact in the further course of the study, only fragments of the Coll-HA membrane were found 30 and 60 days after implantation. Histomorphometrically, it can be described that although initially (at 10 days post-implantation) similar results were found in all study groups, after 30 days post-implantation the cellular penetration depth of the hyaluronic acid-collagen membrane was significantly increased with time (**** p < 0.0001). Similarly, the percentage of cellular invasion per membrane thickness was also significantly higher in the Coll-HA group at all timepoints, compared to the other membranes (**** p < 0.0001). Altogether, these results show that the histomorphometrical analysis of the cellular migration can act as an indicator of integration and duration of barrier functionality. Via this approach, it was possible to semi-quantify the different levels of cellular penetration of GBR membranes that were only qualitatively analyzed through histopathological approaches before. Additionally, the results of the histopathological and histomorphometrical analyses revealed that hyaluronic acid addition to collagen does not lead to a prolonged standing time, but an increased integration of a collagen-based biomaterial. Therefore, it can only partially be used in the dental field for indications that require fast resorbed membranes and a fast cell or tissue influx such as periodontal regeneration processes.
RESUMEN
Collagen-based resorbable barrier membranes have been increasingly utilized for Guided Bone Regeneration (GBR), as an alternative to non-resorbable synthetic membranes that require a second surgical intervention for removal. One of the most important characteristics of a resorbable barrier membrane is its mechanical integrity that is required for space maintenance and its tissue integration that plays a crucial role in wound healing and bone augmentation. This study compares a commercially available porcine-derived sugar-crosslinked collagen membrane with two non-crosslinked collagen barrier membranes. The material analysis provides an insight into the influence of manufacturing on the microstructure. In vivo subcutaneous implantation model provides further information on the host tissue reaction of the barrier membranes, as well as their tissue integration patterns that involve cellular infiltration, vascularization, and degradation. The obtained histochemical and immunohistochemical results over three time points (10, 30, and 60 days) showed that the tissue response to the sugar crosslinked collagen membrane involves inflammatory macrophages in a comparable manner to the macrophages observed in the surrounding tissue of the control collagen-based membranes, which were proven as biocompatible. The tissue reactions to the barrier membranes were additionally compared to wounds from a sham operation. Results suggest wound healing properties of all the investigated barrier membranes. However, the sugar-crosslinked membrane lacked in cellular infiltration and transmembraneous vascularization, providing an exclusive barrier function in GBR. Moreover, this membrane maintained a similar swelling ratio over examined timepoints, which suggests a very slow degradation pattern and supports its barrier function. Based on the study results, which showed biocompatibility of the sugar crosslinked membrane and its stability up to 60 days post-implantation, it can be concluded that this membrane may be suitable for application in GBR as a biomaterial with exclusive barrier functionality, similar to non-resorbable options.
