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Objective: Pigs are emerging as a preferred experimental in vivo model for bone regeneration. The study objective was to answer the focused PEO question: in the pig model (P), what is the capacity of experimental alveolar bone defects (E) for spontaneous regeneration in terms of new bone formation (O)? Methods: Following PRISMA guidelines, electronic databases were searched for studies reporting experimental bone defects or extraction socket healing in the maxillae or mandibles of pigs. The main inclusion criteria were the presence of a control group of untreated defects/sockets and the assessment of regeneration via 3D tomography [radiographic defect fill (RDF)] or 2D histomorphometry [new bone formation (NBF)]. Random effects meta‐analyses were performed for the outcomes RDF and NBF. Results: Overall, 45 studies were included reporting on alveolar bone defects or extraction sockets, most frequently in the mandibles of minipigs. Based on morphology, defects were broadly classified as 'box‐defects' (BD) or 'cylinder‐defects' (CD) with a wide range of healing times (10 days to 52 weeks). Meta‐analyses revealed pooled estimates (with 95% confidence intervals) of 50% RDF (36.87%–63.15%) and 43.74% NBF (30.47%–57%) in BD, and 44% RDF (16.48%–71.61%) and 39.67% NBF (31.53%–47.81%) in CD, which were similar to estimates of socket‐healing [48.74% RDF (40.35%–57.13%) and 38.73% NBF (28.57%–48.89%)]. Heterogeneity in the meta‐analysis was high (I2 > 90%). Conclusion: A substantial body of literature revealed a high capacity for spontaneous regeneration in experimental alveolar bone defects of (mini)pigs, which should be considered in future studies of bone regeneration in this animal model. [ABSTRACT FROM AUTHOR]

Bio-Gide® is a collagen membrane routinely used in guided bone regeneration. Recent studies have shown that this collagen membrane has osteoconductive properties, meaning that it can support the growth of new bone. However, it has also been observed that the collagen membrane has areas of mineralized fibers which can occur spontaneously and independently of osteoblasts. To better understand how this works, we established a model using minced collagen membranes to reduce the active mineralization of intact collagen membranes in favor of passive mineralization. We thus compared the original intact membrane with a minced collagen membrane in a 5 mm calvarial defect model in Sprague Dawley rats. After three weeks of healing, histology and microcomputed tomography (μCT) were performed. Histological analysis confirmed the osteoconductive properties, with new bone growing inside the intact collagen membrane. However, in minced collagen membranes, the osteoconductive properties were restricted to the defect margins. Interestingly, histology revealed large mineralized areas indicating passive mineralization with no signs of bone formation. In the μCT analysis, the intact collagen membranes caused a higher median mineralized volume (1.5 mm3) compared with the minced group (0.4 mm3), but this lacked significance (p = 0.09). The μCT analysis needs to be interpreted carefully, particularly in defects filled with minced membranes, considering that the mineralized tissue may not necessarily be bone but also the result of passive mineralization. Taken together, the findings suggest that Bio-Gide® collagen membranes support bone formation while also exhibiting potential for passive mineralization. [ABSTRACT FROM AUTHOR]

Objectives: Secretomes of mesenchymal stromal cells (MSC) represent a novel strategy for growth‐factor delivery for tissue regeneration. The objective of this study was to compare the efficacy of adjunctive use of conditioned media of bone‐marrow MSC (MSC‐CM) with collagen barrier membranes vs. adjunctive use of conditioned media of leukocyte‐ and platelet‐rich fibrin (PRF‐CM), a current growth‐factor therapy, for guided bone regeneration (GBR). Methods: MSC‐CM and PRF‐CM prepared from healthy human donors were subjected to proteomic analysis using mass spectrometry and multiplex immunoassay. Collagen membranes functionalized with MSC‐CM or PRF‐CM were applied on critical‐size rat calvaria defects and new bone formation was assessed via three‐dimensional (3D) micro‐CT analysis of total defect volume (2 and 4 weeks) and 2D histomorphometric analysis of central defect regions (4 weeks). Results: While both MSC‐CM and PRF‐CM revealed several bone‐related proteins, differentially expressed proteins, especially extracellular matrix components, were increased in MSC‐CM. In rat calvaria defects, micro‐CT revealed greater total bone coverage in the MSC‐CM group after 2 and 4 weeks. Histologically, both groups showed a combination of regular new bone and 'hybrid' new bone, which was formed within the membrane compartment and characterized by incorporation of mineralized collagen fibers. Histomorphometry in central defect sections revealed greater hybrid bone area in the MSC‐CM group, while the total new bone area was similar between groups. Conclusion: Based on the in vitro and in vivo investigations herein, functionalization of membranes with MSC‐CM represents a promising strategy to enhance GBR. [ABSTRACT FROM AUTHOR]