Jellyfish collagen, which can be defined as “collagen type 0” due to its homogeneity to the mammalian types I, II, III, V, and IX and its batch-to-batch consistent producibility, is of special interest for different medical applications related to (bone) tissue regeneration as an alternative to mammalian collagen-based biomaterials. However, no in vivo studies regarding the induction of M1- and M2-macrophages and their time-dependent ration as well as the analysis of the bone regeneration capacity of jellyfish collagen scaffolds have been conducted until now. Thus, the goal of this study was to determine the nature of the immune response to jellyfish collagen scaffolds and their bone healing capacities. Two in vivo studies using established implantation models, i.e., the subcutaneous and the calvarian implantation model in Wistar rats, were conducted. Furthermore, specialized histological, histopathological, and histomorphometrical methods have been used. As a control biomaterial, a collagen scaffold, originating from porcine pericardium, which has already been stated as biocompatible, was used for the subcutaneous study. The results of the present study show that jellyfish collagen scaffolds are nearly completely resorbed until day 60 post implantation by stepwise integration within the subcutaneous connective tissue mediated mainly by macrophages and single multinucleated giant cells. Interestingly, the degradation process ended in a vessel rich connective tissue that is understood to be an optimal basis for tissue regeneration. The study results showed an overall weaker immune response to jellyfish collagen than to porcine pericardium matrices by the induction of significantly lower numbers of macrophages together with a more balanced occurrence of M1- and M2-macrophages. However, both collagen-based biomaterials induced balanced numbers of both macrophage subtypes, which supports their good biocompatibility. Moreover, the histomorphometrical results for the calvarial implantation of the jellyfish scaffolds revealed an average of 46.20% de novo bone formation at day 60, which was significantly higher compared to the control group. Thereby, the jellyfish collagen scaffolds induced also significantly higher numbers of anti-inflammatory macrophages within the bony implantation beds. Altogether, the results show that the jellyfish collagen scaffolds allowed for a directed integration behavior, which is assumed to be in accordance with the concept of Guided Bone Regeneration (GBR). Furthermore, the jellyfish collagen scaffolds induced a long-term anti-inflammatory macrophage response and an optimal vascularization pattern within their implant beds, thus showing excellent biocompatibility and (bone) tissue healing properties.

The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration.

To date, there are no bioresorbable alternatives to non-resorbable and volume-stable membranes in the field of dentistry for guided bone or tissue regeneration (GBR/GTR). Even magnesium (Mg) has been shown to constitute a favorable biomaterial for the development of stabilizing structures. However, it has been described that it is necessary to prevent premature degradation to ensure both the functionality and the biocompatibility of such Mg implants. Different coating strategies have already been developed, but most of them did not provide the desired functionality. The present study analyses a new approach based on ion implantation (II) with PVD coating for the passivation of a newly developed Mg membrane for GBR/GTR procedures. To demonstrate comprehensive biocompatibility and successful passivation of the Mg membranes, untreated Mg (MG) and coated Mg (MG-Co) were investigated in vitro and in vivo. Thereby a collagen membrane with an already shown biocompatibility was used as control material. All investigations were performed according to EN ISO 10993 regulations. The in vitro results showed that both the untreated and PVD-coated membranes were not cytocompatible. However, both membrane types fulfilled the requirements for in vivo biocompatibility. Interestingly, the PVD coating did not have an influence on the gas cavity formation compared to the uncoated membrane, but it induced lower numbers of anti-inflammatory macrophages in comparison to the pure Mg membrane and the collagen membrane. In contrast, the pure Mg membrane provoked an immune response that was fully comparable to the collagen membrane. Altogether, this study shows that pure magnesium membranes represent a promising alternative compared to the nonresorbable volume-stable materials for GBR/GTR therapy.

The physicochemical properties of synthetically produced bone substitute materials (BSM) have a major impact on biocompatibility. This affects bony tissue integration, osteoconduction, as well as the degradation pattern and the correlated inflammatory tissue responses including macrophages and multinucleated giant cells (MNGCs). Thus, influencing factors such as size, special surface morphologies, porosity, and interconnectivity have been the subject of extensive research. In the present publication, the influence of the granule size of three identically manufactured bone substitute granules based on the technology of hydroxyapatite (HA)-forming calcium phosphate cements were investigated, which includes the inflammatory response in the surrounding tissue and especially the induction of MNGCs (as a parameter of the material degradation). For the in vivo study, granules of three different size ranges (small = 0.355–0.5 mm; medium = 0.5–1 mm; big = 1–2 mm) were implanted in the subcutaneous connective tissue of 45 male BALB/c mice. At 10, 30, and 60 days post implantationem, the materials were explanted and histologically processed. The defect areas were initially examined histopathologically. Furthermore, pro- and anti-inflammatory macrophages were quantified histomorphometrically after their immunohistochemical detection. The number of MNGCs was quantified as well using a histomorphometrical approach. The results showed a granule size-dependent integration behavior. The surrounding granulation tissue has passivated in the groups of the two bigger granules at 60 days post implantationem including a fibrotic encapsulation, while a granulation tissue was still present in the group of the small granules indicating an ongoing cell-based degradation process. The histomorphometrical analysis showed that the number of proinflammatory macrophages was significantly increased in the small granules at 60 days post implantationem. Similarly, a significant increase of MNGCs was detected in this group at 30 and 60 days post implantationem. Based on these data, it can be concluded that the integration and/or degradation behavior of synthetic bone substitutes can be influenced by granule size.

Objectives: The present randomized controlled clinical study aimed to investigate if, in lateral maxillary sinus augmentation, the repositioned bony wall or the application of a collagen membrane results in more preferable new hard tissue formation. Materials and methods: Forty patients were divided into two study groups. Both groups received a xenogeneic bone substitute material (BSM) during lateral sinus augmentation. In the bony wall group (BW), following piezosurgery, the retrieved bony wall was repositioned. In the collagen membrane group (CM), following rotary instrument preparation, collagen membrane coverage was applied. After 6 months, biopsies were taken to histologically analyze the percentage of BSM, connective tissue (CT), and newly formed bone (NFB) following both approaches. Results: Forty implants were placed and 29 harvested biopsies could be evaluated. Duration of surgery, membrane perforations, and VAS were detected. Histomorphometrical analysis revealed comparable amounts of all analyzed parameters in both groups in descending order: CT (BW: 39.2 ± 9%, CM: 37,9 ± 8.5%) > BSM (BW: 32.9 ± 6.3%, CM: 31.8 ± 8.8%) > NB (BW: 27.8 ± 11.2%, CM: 30.3 ± 4.5%). Conclusions: The results of the present study show that the closure of the access window by means of the retrieved bony wall or a native collagen membrane led to comparable bone augmentation results. Clinical trial: clinicaltrials.gov NCT04811768. Clinical relevance: Lateral maxillary sinus augmentation with the application of a xenogeneic BSM in combination with a native collagen membrane for bony window coverage represents a reliable method for surgical reconstruction of the posterior maxilla. Piezosurgery with bony window repositioning delivers comparable outcomes without membrane coverage.

(1) Background: The aim of the present study was the biocompatibility analysis of a novel xenogeneic vascular graft material (PAP) based on native collagen won from porcine aorta using the subcutaneous implantation model up to 120 days post implantationem. As a control, an already commercially available collagen-based vessel graft (XenoSure^®) based on bovine pericardium was used. Another focus was to analyze the (ultra-) structure and the purification effort. (2) Methods: Established methodologies such as the histological material analysis and the conduct of the subcutaneous implantation model in Wistar rats were applied. Moreover, established methods combining histological, immunohistochemical, and histomorphometrical procedures were applied to analyze the tissue reactions to the vessel graft materials, including the induction of pro- and anti-inflammatory macrophages to test the immune response. (3) Results: The results showed that the PAP implants induced a special cellular infiltration and host tissue integration based on its three different parts based on the different layers of the donor tissue. Thereby, these material parts induced a vascularization pattern that branches to all parts of the graft and altogether a balanced immune tissue reaction in contrast to the control material. (4) Conclusions: PAP implants seemed to be advantageous in many aspects: (i) cellular infiltration and host tissue integration, (ii) vascularization pattern that branches to all parts of the graft, and (iii) balanced immune tissue reaction that can result in less scar tissue and enhanced integrative healing patterns. Moreover, the unique trans-implant vascularization can provide unprecedented anti-infection properties that can avoid material-related bacterial infections.