Search Results (13)

Background and Objectives: The purpose of this case report is to examine the management of vestibular bone fenestration during alveolar socket preservation using the Periosteal Inhibition (PI) approach. Here, for the first time, the PI technique, which has been shown to be successful in maintaining intact cortical bone, is examined in the context of a bone defect. Materials and Methods: After an atraumatic extraction of a damaged tooth, a vestibular bone fenestration was discovered in the 62-year-old male patient. To shield the defect, a non-resorbable PTFE membrane (OSSEO GUARD by Zimmer Biomet) was positioned between the mucosa and the fenestration site. A resorbable porcine gelatin sponge (SPONGOSTAN^TM) was used to achieve hemostasis, and a 5/0 PGCL absorbable suture was used to close the wound. A CBCT scan was performed, and a dental implant was inserted after 4 months. Results: After 4 months, the case demonstrated positive results, with full cortical remodeling and preservation of the original bone proportions. The fenestration completely healed, proving that the PI approach works even in the presence of bone flaws in cortical bone that is still intact. Conclusions: This is the first case report that shows that vestibular bone fenestration can be successfully treated with the PI approach. It has now been demonstrated that the procedure, which hitherto needed an undamaged cortical bone to work, can help bone abnormalities to repair completely. These results imply that the PI technique is a flexible and useful approach that provides predictable results in dental surgery for treating different types of alveolar bone abnormalities. Its use might be expanded with more study to include bone dehiscence treatment. Full article

Fracture healing is a complex series of events that requires a local inflammatory reaction to initiate the reparative process. This inflammatory reaction is important for stimulating the migration and proliferation of mesenchymal progenitor cells from the periosteum and surrounding tissues to form the cartilaginous and bony calluses. The proinflammatory cytokine interleukin (IL)-17 family has gained attention for its potential regenerative effects; however, the requirement of IL-17 signaling within mesenchymal progenitor cells for normal secondary fracture healing remains unknown. The conditional knockout of IL-17 receptor a (Il17ra) in mesenchymal progenitor cells was achieved by crossing Il17ra^F/F mice with Prx1-cre mice to generate Prx1-cre; Il17ra^F/F mice. At 3 months of age, mice underwent experimental unilateral mid-diaphyseal femoral fractures and healing was assessed by micro-computed tomography (µCT) and histomorphometric analyses. The effects of IL-17RA signaling on the osteogenic differentiation of fracture-activated periosteal cells was investigated in vitro. Examination of the intact skeleton revealed that the conditional knockout of Il17ra decreased the femoral cortical porosity but did not affect any femoral trabecular microarchitectural indices. After unilateral femoral fractures, Il17ra conditional knockout impacted the cartilage and bone composition of the fracture callus that was most evident early in the healing process (day 7 and 14 post-fracture). Furthermore, the in vitro treatment of fracture-activated periosteal cells with IL-17A inhibited osteogenesis. This study suggests that IL-17RA signaling within Prx1+ mesenchymal progenitor cells can influence the early stages of endochondral ossification during fracture healing. Full article

The implementation of a successful therapeutic approach that includes tissue-engineered grafts requires detailed analyses of graft-immune cell interactions in order to predict possible immune reactions after implantation. The phenotypic plasticity of macrophages plays a central role in immune cell chemotaxis, inflammatory regulation and bone regeneration. The present study addresses effects emanating from JPC-seeded β-TCP constructs (3DJPCs) co-cultivated with THP-1 derived M1/M2 macrophages within a horizontal co-culture system. After five days of co-culture, macrophage phenotype and chemokine secretion were analyzed by flow cytometry, quantitative PCR and proteome arrays. The results showed that pro-inflammatory factors in M1 macrophages were inhibited by 3DJPCs, while anti-inflammatory factors were activated, possibly affected by the multiple chemokines secreted by 3D-cultured JPCs. In addition, osteoclast markers of polarized macrophages were inhibited by osteogenically induced 3DJPCs. Functional assays revealed a significantly lower percentage of proliferating CD4⁺ T cells in the groups treated with secretomes from M1/M2 macrophages previously co-cultured with 3DJPCs compared to controls without secretomes. Quantifications of pit area resorption assays showed evidence that supernatants from 3DJPCs co-cultured with M1/M2 macrophages were able to completely suppress osteoclast maturation, compared to the control group without secretomes. These findings demonstrate the ability of 3D cultured JPCs to modulate macrophage plasticity. Full article

In this manuscript, the authors propose a new technique for inserting implants immediately into the sockets corresponding to the lower first molars and, in any case, in the sockets in which the alveolar septum is still present. Immediate post-extraction implants are a widely discussed topic in the literature. Most authors currently consider the insertion of implants immediately after extraction less useful in terms of the procedure’s questionable benefits in maintaining the height of the alveolar bone and more useful in terms of lessening patients’ discomfort. Due to the anatomy of the post-extraction socket and its traditionally cylindrical geometry, this procedure is not always possible.: Next-generation REX-type blade implants were used via their insertion into the septum accompanied by a cortical lamina for periosteal inhibition without filling any of the alveoli.: In the 20 patients treated, the REX implant proved to be stable and surrounded by newly formed bone at the 18-month follow-up. This simple, easily employable technique allows an implant to be inserted immediately after extraction and in the same surgical session, with good patient compliance and good preservation of the alveolus due to the facilitation of periosteal inhibition. The excellent clinical results obtained with the use of a blade implant in the posterior sectors suggest that it is possible to reduce surgical sessions even in conditions of post-extraction sockets whose septum alone can ensure the primary stability essential for osseointegration. The use of a larger number of patients will also provide us with significant statistical results in support of this preliminary clinical work. New clinical studies are needed to understand the true potential of this method for application in daily clinical practice. Full article

An increased risk of non-pathological fractures in patients with prostate cancer and bone metastases has been associated with combination treatment with radium-223, abiraterone, and prednisone/prednisolone in the absence of bone-protecting agents. Here, we investigated possible mechanisms leading to this outcome using an intratibial LNCaP model mimicking prostate cancer bone metastases. Male NOD.scid mice were inoculated intratibially with LNCaP prostate cancer cells and treated with vehicle, radium-223, abiraterone, prednisone, zoledronic acid, or their combinations for 28 days. Serum TRACP 5b and PSA levels were measured. Bone structure, quality, and formation rate of non-tumor-bearing and tumor-bearing tibiae were analyzed by microCT, 3-point bending assay, and dynamic histomorphometry, respectively. Radium-223 incorporation into bone was also measured. Radium-223/abiraterone/prednisone combination treatment induced a transient increase in bone resorption indicated by elevated TRACP 5b levels, which was inhibited by concurrent treatment with zoledronic acid. Furthermore, radium-223/abiraterone/prednisone combination reduced periosteal and trabecular new bone formation and the number of osteoblasts, but bone structure or biomechanical quality were not affected. The abiraterone/prednisone treatment decreased radium-223 incorporation into tumor-bearing bone, possibly explaining the lack of additional antitumor efficacy. In conclusion, radium-223/abiraterone/prednisone combination increased bone resorption, which may have been one of the mechanisms leading to an increased fracture risk in patients with mCRPC. Full article

Background: Alveolar socket preservation is a topic of serious interest, and researchers have investigated this problem quite extensively. In terms of aesthetics, it is very important to avoid bone resorption if the clinician decides to insert the implant immediately after the extraction. Recently, a new approach utilizing a barrier external to the socket has been developed, which has advanced the evolution of this technique. Immediate implants have also created some difficulty when re-evaluated in long-term follow-up, especially when an aesthetic result is part of the goal of the procedure. Methods: The modified periosteal inhibition (MPI) technique, which has shown interesting outcomes, is evaluated in this paper on a large group of patients. In this case series, among 14 patients, 11 received immediate implants using the MPI technique and immediate provisionalization, and 3 received immediate implants using the MPI technique and customized healing abutment. All patients showed ridge preservation to different degrees, ranging from 0.02 to 1.17 mm, with an average gain of 0.51 mm. Results: all of the 14 patients maintained the original ridge shape, and 1 showed an increase in bucco-lingual size. Conclusions: This case series confirms the promising information reported in earlier studies on this technique. Larger samples will be necessary to confirm the predictability of this new approach. Full article

Several Alveolar Ridge Preservation (ARP) procedures have been proposed over the years. The purpose of this study was to describe the new Modified Periosteal Inhibition (MPI) technique for ARP. Seven patients were enrolled (age range: 28–72 years old; 5 males, 2 females). In total, nine hopeless teeth were treated. Following the elevation of a full-thickness flap, atraumatic tooth extraction was conducted, preserving the buccal bone of the alveolar socket. OsteoBiol^® Lamina Soft (Tecnoss^®, Giaveno, Italy), 0.5 mm thick, was suitably shaped (8–10 mm in height, extending from the mesial and to the distal corners of the socket). The lamina was gently positioned between the buccal periosteum and the buccal bone plate. Tisseel^® (Baxter Healthcare Corporation, Deerfield, IL, USA) was applied to seal the cortical membrane. The flaps were sutured with PTFE 4-0 (Omnia, Fidenza, Italy). Postoperative instructions were provided. Patients were strictly monitored during the follow-up. No early or late biological complications were experienced. Cone Beam Computed Tomography (CBCT) exams were performed at baseline and 4 months later. The thickness of the buccal cortical bone at baseline was 1.18 ± 0.57 mm. The pre-operative and post-operative ridge widths were 10.74 ± 1.54 mm and 11.16 ± 1.57 mm, respectively. A horizontal ridge increase of 0.41 ± 0.21 mm was observed during the healing period. At 4 months of healing, the bone volume was adequate for implant placement and no additional bone regeneration procedures were required. MPI technique was effective in preventing the horizontal contraction of the post-extraction socket. Further studies will be needed in the future to confirm our positive results. Full article

A compromised extraction socket is characterized by severe bone resorption around neighboring teeth and is often occupied with thick intrasocket granulation tissue (IGT). Guided bone regeneration (GBR) is a procedure that can preserve the bone volume around extraction sockets, and it can also be combined with immediate implant placement. However, an early exposure of GBR sites is a possible complication because it increases the risk of infection and can inhibit successful bone regeneration. The purpose of these case series is to introduce a novel, surgical procedure that can prevent the exposure of GBR sites by using IGT for flap extension during immediate implant placement in compromised extraction sockets. The technique was successfully performed in six patients. For successful flap closure, the inner portion of the IGT was dissected so that the flap was properly extended with the base of IGT attached to the flap for blood supply. Periosteal releasing incisions were not performed. The IGT was first sutured to the palatal flap with resorbable sutures, and then the overlying flap was closed with additional sutures. There was no post-operative exposure of the surgical GBR site in any of the patients, and the location of the mucogingival junction remained unchanged. All grafted sites also achieved sufficient bone regeneration. Within the limitations, this case series demonstrates the potential use of IGT, a concept which was previously obsolete. Full article

We recently reported an unexpected role of osteoblast-derived matrix vesicles in the delivery of microRNAs to bone matrix. Of such microRNAs, we found that miR-125b inhibited osteoclast formation by targeting Prdm1 encoding a transcriptional repressor of anti-osteoclastogenesis factors. Transgenic (Tg) mice overexpressing miR-125b in osteoblasts by using human osteocalcin promoter grow normally but exhibit high trabecular bone mass. We have now further investigated the effects of osteoblast-mediated miR-125b overexpression on skeletal morphogenesis and remodeling during development, aging and in a situation of skeletal repair, i.e., fracture healing. There were no significant differences in the growth plate, primary spongiosa or lateral (periosteal) bone formation and mineral apposition rate between Tg and wild-type (WT) mice during early bone development. However, osteoclast number and medial (endosteal) bone resorption were less in Tg compared to WT mice, concomitant with increased trabecular bone mass. Tg mice were less susceptible to age-dependent changes in bone mass, phosphate/amide I ratio and mechanical strength. In a femoral fracture model, callus formation progressed similarly in Tg and WT mice, but callus resorption was delayed, reflecting the decreased osteoclast numbers associated with the Tg callus. These results indicate that the decreased osteoclastogenesis mediated by miR-125b overexpression in osteoblasts leads to increased bone mass and strength, while preserving bone formation and quality. They also suggest that, in spite of the fact that single miRNAs may target multiple genes, the miR-125b axis may be an attractive therapeutic target for bone loss in various age groups. Full article

Mesenchymal stem cells (MSCs) have gained attraction not only in the field of regenerative medicine but also in the field of autoimmune disease therapies or organ transplantation due to their immunoregulatory and/or immunosuppressive features. Dendritic cells (DCs) play a crucial role in initiating and regulating immune reactions by promoting antigen-specific T cell activation. In this study, we investigated the effect of human jaw periosteal progenitor cells (JPCs) seeded in beta-tricalcium phosphate (β-TCP) scaffolds on monocyte-derived DC differentiation. Significantly lower numbers of differentiated DCs were observed in the presence of normal (Co) and osteogenically induced (Ob) JPCs-seeded β-TCP constructs. Gene expression analysis revealed significantly lower interleukin-12 subunit p35 (IL-12p35) and interleukin-12 receptor beta 2 (IL-12Rβ2) and pro-inflammatory cytokine interferon-gamma (IFN-γ) levels in DCs under Ob conditions, while interleukin-8 (IL-8) gene levels were significantly increased. Furthermore, in the presence of JPCs-seeded β-TCP constructs, interleukin-10 (IL-10) gene expression was significantly induced in DCs, particularly under Ob conditions. Analysis of DC protein levels shows that granulocyte-colony stimulating factor (G-CSF) was significantly upregulated in coculture groups. Our results indicate that undifferentiated and osteogenically induced JPCs-seeded β-TCP constructs have an overall inhibitory effect on monocyte-derived DC maturation. Full article

Background: The biological mechanisms that contribute to atrophic long bone non-union are poorly understood. Multipotential mesenchymal stromal cells (MSCs) are key contributors to bone formation and are recognised as important mediators of blood vessel formation. This study examines the role of MSCs in tissue formation at the site of atrophic non-union. Materials and Methods: Tissue and MSCs from non-union sites (n = 20) and induced periosteal (IP) membrane formed following the Masquelet bone reconstruction technique (n = 15) or bone marrow (n = 8) were compared. MSC content, differentiation, and influence on angiogenesis were measured in vitro. Cell content and vasculature measurements were performed by flow cytometry and histology, and gene expression was measured by quantitative polymerase chain reaction (qPCR). Results: MSCs from non-union sites had comparable differentiation potential to bone marrow MSCs. Compared with induced periosteum, non-union tissue contained similar proportion of colony-forming cells, but a greater proportion of pericytes (p = 0.036), and endothelial cells (p = 0.016) and blood vessels were more numerous (p = 0.001) with smaller luminal diameter (p = 0.046). MSCs showed marked differences in angiogenic transcripts depending on the source, and those from induced periosteum, but not non-union tissue, inhibited early stages of in vitro angiogenesis. Conclusions: In vitro, non-union site derived MSCs have no impairment of differentiation capacity, but they differ from IP-derived MSCs in mediating angiogenesis. Local MSCs may thus be strongly implicated in the formation of the immature vascular network at the non-union site. Attention should be given to their angiogenic support profile when selecting MSCs for regenerative therapy. Full article

Clinical application of tissue engineering products requires the exclusion of immune responses after implantation. We used jaw periosteal cells (JPCs) as a suitable stem cell source and analyzed herein the effects of JPCs on dendritic cell maturation after co-culturing of both cell types. Peripheral blood mononuclear cells (PBMCs) were differentiated to dendritic cells (DCs) by the addition of differentiation cocktails for 7 days in co-culture with undifferentiated and osteogenically induced JPCs. The effects of JPCs on DC maturation were analyzed at the beginning (day 7), in the middle (day 14), and at the end (day 21) of the osteogenesis process. We detected significantly lower DC numbers after co-culturing with JPCs that have previously been left untreated or osteogenically differentiated for 7, 14, and 21 days. Using gene expression analyses, significantly lower IL-12p35 and -p40 and pro-inflammatory cytokine (IFN-γ and TNF-α) levels were detected, whereas IL-8 mRNA levels were significantly higher in DCs. Furthermore, osteogenic media conditions enhanced significantly IL-10 gene expression. We concluded that undifferentiated and osteogenically differentiated JPCs had an overall inhibiting influence on dendritic cell maturation. Further studies should clarify the underlaying mechanism in depth. Full article

HCl-demineralized murine lower incisors were implanted intramuscularly into syngeneic BALB/c mice to induce heterotopic osteogenesis. Implants were exposed at the early, preosteogenic stage (4), or at the later, osteogenic stage (12) to the Moloney sarcoma virus (MSV), which within 3–4 days results in a sarcoma. The yield of bone induction was determined by weight of dry bone mass following NaOH hydrolysis of soft tissues. To verify the effect of this sarcoma on orthotopic local femoral bone, the dry mass of the tumor-exposed femora was measured and compared with the weight of MSV-unexposed contralateral controls. MSV-sarcoma or cells involved with their spontaneous rejection have a stimulatory effect on the periosteal membrane of the tumor-adjacent femoral bones, increasing their dry mass on average by 18%. No stimulatory effect on heterotopic bone induction was observed when the MSV sarcoma grew during the early, preosteogenic stage (4 onward), but when the tooth matrix had been exposed to such tumor at the already bone-forming stage, (12 onward), the yield of bone induction was enhanced. Thus, it is postulated that lesions induced by MSV during the early, preosteogenic stage inhibit recruitment of osteoprogenitor cells or degrade Bone Morphogenetic Proteins (BMPs) released by matrix resorbing inflammatory cells, whereas when acting on already existing bone they have a stimulatory effect. Full article