Mike Barbeck

Alveolar ridge preservation (ARP) remains challenging in extraction sockets, particularly in the presence of buccal bone dehiscence, where post‐extraction remodeling predominantly affects the coronal ridge. The Biologically‐oriented Alveolar Ridge Preservation (BARP) concept and its modified application for compromised sockets (mBARP) were developed as innovative biologically driven protocols based on selective compartmentalized grafting. Instead of completely filling the socket, these approaches preserve spontaneous healing in the apical compartment while reinforcing the coronal portion, where dimensional changes are greatest. The protocols combine a collagen sponge in the apical part of the socket with xenograft particles and a collagen sponge sealing the coronal compartment. In compromised sockets, an additional collagen sponge is positioned between the residual buccal or lingual wall and the mucoperiosteal flap to enhance graft containment and soft tissue support. Thirty extraction sites were treated using this approach. After 4–6 months, ridge dimensions were effectively preserved, with a slight vertical loss (+0.3 mm), limited horizontal reduction (0.7–1.0 mm), controlled buccal soft tissue contraction (2.0–2.2 mm), and substantial new bone formation (38%–40%), while residual graft particles remained mainly confined to the coronal compartment. Within the limitations of this study, the BARP concept and its modified application demonstrated favorable clinical, radiographic, and histological outcomes, supporting selective coronal grafting as an innovative strategy to preserve ridge dimensions while maintaining physiological healing in the deeper portion of the extraction socket.

Resorbable magnesium (Mg) membranes have been introduced for guided bone regeneration (GBR) to provide space maintenance without removal surgery. This prospective observational study evaluated clinical outcomes and postoperative events after GBR using a Mg membrane (NOVAMag^®) with optional Mg screw fixation. In a single-center cohort, 126 patients underwent 195 GBR-related procedures using a pure Mg membrane with optional Mg fixation screws. Follow-ups were performed up to three months. Outcomes included treatment success, wound dehiscence, clinically evident gas accumulation, and patient-reported recovery (pain/swelling duration). Treatment success was 94.9%. Gas accumulation occurred in 6.2% overall. Wound dehiscence occurred in 10.5%. Mean pain and swelling duration were 4.6 and 4.5 days (median 3 days each). NOVAMag^® enabled GBR with high treatment success and short symptomatic recovery, with manageable rates of postoperative gas accumulation and wound dehiscence in this observational cohort.

Lymphocytes, long regarded as central actors of adaptive immunity, are increasingly recognized as key regulators of the foreign body response (FBR) to biomaterials. Their presence shapes the chronic phases of inflammation, fibrosis, angiogenesis, and regenerative outcomes after implantation. This review summarizes the roles of T cells, B cells, and natural killer (NK) cells in biomaterial-associated immune responses, with a particular focus on protein adsorption, antigen recognition, cytokine secretion, and downstream interactions with macrophages, fibroblasts, and endothelial cells. Evidence indicates that T-cell polarization into Th1/Th17 subsets promotes pro-inflammatory reactions, while Th2 and regulatory T cells (Tregs) support constructive remodeling and resolution. B cells contribute through antibody production and cytokine release, which may foster fibrosis or support debris clearance. NK cells serve as early stress sensors, releasing cytotoxic mediators and pro-angiogenic factors that influence vascularization and tissue repair. Collectively, lymphocytes are pivotal but underexplored players in biomaterial integration. Incorporating lymphocyte biology into material design and surface modification strategies offers promising avenues to guide immune cascades toward predictable and regenerative outcomes.

Biologic enhancement of bone grafts with enamel matrix derivative (EMD) may improve regenerative outcomes by modulating the host tissue response. This study evaluated the in vivo tissue reaction to a biphasic bone substitute (Maxresorb^®), used alone or in combination with EMD, in a subcutaneous mouse model. Forty BALB/c mice received subcutaneous implants of Maxresorb^®, EMD, Maxresorb^® + EMD, or underwent sham surgery. Tissue samples were harvested at 15- and 30-days post-implantation. Histological and immunohistochemical analyses were performed to assess inflammation, neovascularization, fibrosis, and the presence of macrophages and biomaterial-associated multinucleated giant cells (BMGCs). Statistical analysis was conducted using ANOVA (p≤0.05). The Maxresorb^® + EMD group showed higher inflammatory scores, increased numbers of macrophages and BMGCs, and enhanced neovascularization compared with the other groups, particularly at 30 days. Despite this elevated cellular activity, all test conditions were classified as non-irritant or slightly irritant according to ISO 10993-6. The combination of EMD and Maxresorb^® enhanced early tissue responses without adverse effects. These findings support the biocompatibility of this combination and suggest potential regenerative benefits through biologically driven material functionalization.

Background/Aim: Maxillary sinus floor elevation is a well-established procedure for increasing bone volume in the posterior maxilla, yet the regenerative outcome depends strongly on the choice of grafting material. This clinical study compared a high-temperature sintered xenograft (Bio-Oss^®) and a low-temperature processed xenograft (Ti-Oss^®) with regard to their regenerative and immunological profiles. Patients and Methods: Eight patients underwent split-mouth sinus augmentation with both materials, and biopsies were retrieved at 6 months after implant placement. Histological, histomorphometrical, and immunohistochemical analyses were performed to assess bone formation, material resorption, and tissue compatibility. Immunohistochemistry was applied to evaluate the local immune response, focusing on macrophage polarization and multinucleated giant cell activity. Quantitative histomorphometry determined the relative areas of newly formed bone, residual graft material, and connective tissue. Results: Histopathological and histomorphometrical analyses demonstrated comparable levels of new bone formation in both groups, confirming reliable osteoconduction. Immunohistochemical evaluation revealed tartrate-resistant acid phosphatase isoform 5a (TRAP5A) expression in multinucleated giant cells adherent to both materials. Interestingly, Bio-Oss^® induced a higher proportion of anti-inflammatory (CD163⁺) macrophages, whereas Ti-Oss^® triggered a significantly greater number of pro-inflammatory multinucleated giant cells (CD11c⁺). Conclusion: These findings indicate that although both xenogeneic substitutes (Bio-Oss^® and Ti-Oss^®) achieve bone regeneration, they elicit distinct immune responses, which may influence long-term remodeling and graft integration. Consideration of osteoimmunological properties is therefore essential when selecting biomaterials for clinical sinus augmentation.

Granulocytes, long considered short-lived effector cells, are increasingly recognized as key modulators of the foreign body response (FBR) to biomaterials and determinants of regenerative outcomes. This review summarizes current evidence on the roles of neutrophils, basophils, and eosinophils in biomaterial-associated inflammation and tissue remodeling. Particular focus is placed on protein adsorption, cytokine release, and downstream effects across diverse biomaterial classes, including bone substitutes, collagen scaffolds, titanium, magnesium, and synthetic polymers. Neutrophils dominate the acute phase through reactive oxygen species, proteases, and neutrophil extracellular traps, which can either support remodeling or drive fibrosis and implant failure. Basophils, though rare, release histamine and Th2 cytokines, enhancing angiogenesis but also contributing to fibrotic encapsulation. Eosinophils are recruited in material-dependent patterns, releasing cytotoxic granules and pro-regenerative mediators, thereby functioning as double-edged regulators of degradation, fibrosis, and vascularization. Overall, granulocytes act as critical, though often overlooked, determinants of biomaterial integration. Incorporating granulocyte biology into biomaterial design–through modulation of surface chemistry, protein adsorption, and degradation kinetics– offers a promising path to guide inflammatory cascades toward constructive remodeling, angiogenesis, and predictable clinical performance.

Background/Aim: This study compares the biocompatibility of a novel hybrid bone substitute material based on biphasic granules in a type I collagen scaffold using both subcutaneous and calvarial implantation models, in accordance with DIN EN ISO 10993-6. Given the distinct biological environments, materials may exhibit different behaviors in connective versus bone tissue. The aim was to evaluate irritation scores and cellular tissue responses to better understand the material’s performance in both settings. Materials and Methods: This study evaluated the biocompatibility and host tissue response of test materials in male Wistar rats through subcutaneous and calvaria implantation models, following DIN EN ISO 10993-6, assessing cellular responses, material degradation, and bone regeneration at 10-, 30-, and 60-days post-implantation. Results: Subcutaneous implants elicited a stronger inflammatory reaction with higher counts of polymorphonuclear cells, lymphocytes, multinucleated giant cells, and plasma cells at day 10, alongside consistently elevated irritancy scores. In contrast, calvaria implants showed increased neovascularization, reflecting bone-specific regenerative processes. Although capsule formation and cellular infiltration were similar between models, material degradation and phagocytosis were significantly greater subcutaneously at day 60. Conclusion: These results highlight the critical impact of implantation site on immune activation, vascularization, and biomaterial resorption, underlining the importance of model selection in preclinical biomaterial assessment.

Background/Aim: The aim of the present research is a comprehensive evaluation of a fish-collagen based wound membrane using established ex vivo, in vitro and in vivo methodologies. A porcine pericardium membrane served as control material. Materials and Methods: Scanning electron microscopy (SEM) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis were initially used to analyze the structure and collagen molecular structure. Also, a comparison of protein adsorption via measurement of human serum albumin (HSA) adsorption was conducted. The membrane influence on cell viability, cell proliferation as well as their cytotoxic potential were examined in vitro. Additionally, the membrane tissue integration, degradation behavior and biocompatibility were investigated using the subcutaneous implantation model. Results: The SEM analysis showed differences in the structure and the porosity of both membranes. The analysis via FTIR spectroscopy revealed that collagen molecules are present in both membranes in their triple helical structure. The adsorption measurements showed that the surface density of HSA adsorbed to the fish collagen membrane surfaces was significantly lower compared to the values measured for the bovine pericardium membrane. Furthermore, both membranes demonstrated sufficient in vitro cytocompatibility in the indirect colorimetric XTT, LDH and BrdU assays. The in vivo study part revealed that the fish collagen membrane induced a faster biodegradation and a more pronounced pro-inflammatory tissue response, whereas the bovine pericardium membrane degrades more slowly. Conclusion: The results of this study highlight the potential of fish collagen membranes as biocompatible wound healing materials. However, their rapid degradation presents a challenge that needs to be addressed through targeted modifications, such as optimized cross-linking.

Mineralized allogeneic bone substitutes are ideal biomaterials for bone regeneration in surgeries. Moreover, they are also suitable for releasing antibiotics, delivering initial concentrations many times higher than the minimal inhibitory concentration for relevant bacterial strains, without delaying bone formation. In the present study, the potential of sustained-release long-term antibiotic delivery using allografts was investigated. A broad spectrum of antibiotics, including gentamicin, vancomycin, rifampicin, and clindamycin, was incorporated into the bone blocks using a poly-L-lactic acid (PLLA) polymer coating. An in-vivo model of implantation within the rabbit tibia plateau was used to track the sustained release of single/combined antibiotics for up to 120 days. Bony integration and tissue responses to the PLLA-coated antibiotic-delivery systems were analyzed at 4 months post implantation using histopathological analysis. The variant loaded with both vancomycin and rifampicin demonstrated the highest activity against methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermidis. Histopathological analysis revealed that the tissue responses to the coated allogeneic bone substitutes were comparable in all study groups, with no observable histopathological differences. The coated bone blocks induced a strong foreign-body reaction, including high numbers of multinucleated giant cells and other immune cells but no material-associated bone growth. Based on these results, future optimization can focus on selecting more efficient release of antibiotics and increasing the encapsulated concentration to sustain antibiotic release over 4 months, thereby improving the bacteriostatic effect in vivo. Furthermore, biocompatibility and osteoconductivity must be improved.

Background/Aim: The present study aimed to compare the tissue responses to biomaterials in the chick chorioallantoic membrane (CAM) model with those from the subcutaneous implantation model in rats at an early time point. It was especially investigated whether histopathological scoring according to DIN EN ISO 10993-6 is also possible after biomaterial implantation using the CAM model and to what extent the values differ from the data obtained from small animal experiments. Materials and Methods: Implantation of a xenogeneic bone substitute using the CAM model for 24 h and subcutaneous implantation model in rats up to 10 days post implantation were conducted. Standardized histological and histopathological methods were used to apply for histopathological scoring according to DIN EN ISO 10993-6. Results: The histological analysis as well as the histo-pathological scoring revealed that the tissue responses to the xenogeneic bone substitute were completely comparable in both organisms with no visible or statistical differences. Conclusion: We suggest that bioincompatible biomaterials can already be sorted out in the context of THE preclinical in vivo test phase. Such pre-testing before the required small animal tests might clearly contribute to the 3R-concept to reduce the number of animals (REDUCE).