Increase In New Bone Formation Research Articles

Evaluating the Role of Nanoparticles in Enhancing Bone Regeneration in Dental Implantology

ABSTRACT Background: Dental implantology has witnessed substantial progress in recent years, driven by a growing emphasis on optimizing bone regeneration around dental implants. Nanoparticles have emerged as a potential tool for enhancing osseointegration and bone tissue regeneration Materials and Methods: This human clinical trial enrolled 60 adult participants requiring dental implants. Patients were randomly assigned to one of two groups: a control group receiving conventional dental implants, and an experimental group receiving dental implants with nanoparticle-coated surfaces. Radiographic imaging, histological analysis of bone biopsies, and implant stability assessments were conducted at three and six months post-implantation. Results: Histological examination of bone biopsies revealed a statistically significant increase in new bone formation in the experimental group compared to the control group at both three and six months (P < 0.05). Radiographic assessment demonstrated a 25% higher bone density around nanoparticle-coated implants (P < 0.01) at the six-month mark. Implant stability quotient (ISQ) measurements indicated a 20% greater stability in the experimental group (P < 0.05) at the same time point Conclusion: This human clinical trial provides strong evidence that the incorporation of nanoparticles on dental implant surfaces enhances bone regeneration and osseointegration in a human population.

Scaffold-Free Bone Marrow-Derived Mesenchymal Stem Cell Sheets Enhance Bone Formation in a Weight-Bearing Rat Critical Bone Defect Model.

Researchers have been exploring alternative methods for bone tissue engineering, as current management of critical bone defects may be a significant challenge for both patient and surgeon with conventional surgical treatments associated with several potential complications and drawbacks. Recent studies have shown mesenchymal stem cell sheets may enhance bone regeneration in different animal models. We investigated the efficacy of implanted scaffold-free bone marrow-derived mesenchymal stem cell (BMSC) sheets on bone regeneration of a critical bone defect in a weight-bearing rat model. BMSCs were isolated from the femora of male Sprague-Dawley rats 5-6 weeks of age and cell sheets were produced on temperature-responsive culture dishes. Nine male Sprague-Dawley rats 6-8 weeks of age were utilized. A bilateral femoral critical bone defect was created with a bridge plate serving as internal fixation. One side was randomly selected and BMSC sheets were implanted into the bone defect (BMSC group), with the contralateral side receiving no treatment (control). Rats were anesthetized and radiographs were performed at 2-week intervals. At the 8-week time point, rats were euthanized, femurs harvested, and microcomputed tomography and histological analysis was performed. We found a statistically significant increase in new bone formation and bone volume fraction compared with the control. Histomorphometry analysis revealed a larger percent of newly formed bone and a higher total histological score. Our results suggest that scaffold-free BMSC sheets may be used in the management of large weight-bearing bone defects to complement a different surgical technique or as a standalone approach followed by internal fixation. However, further research is still needed.

Histological evaluation of tissue reaction and new bone formation of different calcium silicate-based cements in rats.

The purpose of this study was to evaluate the local reactions and new bone formation of rat subcutaneous and bone tissue to different calcium silicate cements. In this study, 80 rats were divided into five groups as control, BIOfactor MTA (BIO), NeoMTA Plus (NEO), MTA Repair Hp (REP), Biodentine (DENT) and then into two subgroups according to sacrification times (7, 30 days; n = 8). Polyethylene tubes filled with appropriate materials (test groups); empty tubes (control group) were implanted into the dorsum of each rat subcutaneously. For intraosseous implantation, materials were placed in the cavities created in tibia of rats. Subcutaneous tissue and tibia samples were stained with haematoxylin-eosin and subjected to histopathological analysis. A score (0-3) was used to grade inflammatory reaction and new bone formation. Data were analysed by Kruskal-Wallis and Mann-Whitney U tests (P < 0.05). Inflammatory reaction observed in subcutaneous and intraosseous tissues for 7 days decreased significantly in all groups over time (P < 0.05). It was determined that there was significant increase in new bone formation in REP, BIO, DENT groups over time (P < 0.05). Four contemporary bioceramic materials induced local inflammation and tissues changes shortly after subcutaneous implantation, which were reduced over time. In ıntraosseous implantation, all materials induced new bone formation over time. ADJ-03-23-0134. © 2023 Australian Dental Association.

Paget s disease with angioid streaks of the retina

Angioid streaks are a striking fundus change produced by linear breaks in Bruch’s membrane. First described in 1889 by Doyne in a patient with retinal hemorrhages secondary to trauma. They are most often associated with pseudoxanthoma elasticum, but there have been a number of cases reported in connection with other conditions, such as Paget’s disease, which is a localized disorder of bone remodeling characterized by the increase in bone resorption followed by an increase in new bone formation, altering bone architecture. Angioid streaks are present in 10 to 15% of patients with Paget’s disease. It was aimed to share this case report to underline the rarity of this combination.

Paget’s Disease with Angioid Streaks of the Retina: Case Report

Angioid streaks are a striking fundus change produced by linear breaks in Bruch’s membrane. First described in 1889 by Doyne in a patient with retinal hemorrhages secondary to trauma. They are most often associated with pseudoxanthoma elasticum, but there have been a number of cases reported in connection with other conditions, such as Paget’s disease, which is a localized disorder of bone remodeling characterized by the increase in bone resorption followed by an increase in new bone formation, altering bone architecture. Angioid streaks are present in 10 to 15% of patients with Paget’s disease. It was aimed to share this case report to underline the rarity of this combination.

BIODEGRADABLE MAGNESIUM COMBINED WITH DISTRACTION OSTEOGENESIS SYNERGISTICALLY STIMULATES BONE TISSUE REGENERATION

Critical size bone defects are frequently caused by accidental trauma, oncologic surgery, and infection. Distraction osteogenesis (DO) is a useful technique to promote the repair of critical size bone defects. However, DO is usually a lengthy treatment, therefore accompanied with increased risks of complications such as infections and delayed union.Herein, we developed an innovative intramedullary biodegradable magnesium (Mg) nail to accelerate bone regeneration in critical size bone defect repair during DO.We observed that Mg nail induced almost 4-fold increase of new bone formation and over 5-fold of new vessel formation at 2 weeks after distraction. Mg nail upregulated the expression of calcitonin gene-related peptide (CGRP) in the new bone as compared with the DO alone group. We further revealed that blockade of the sensory nerve by overdose capsaicin blunted Mg nail enhanced critical size bone defect repair during the DO process. Moreover, inhibitors/antagonist of CGRP receptor, FAK, and VEGF receptor blocked the Mg nail stimulated vessel and bone formation.In summary, we revealed, for the first time, a CGRP-FAK-VEGF signaling axis linking sensory nerve and endothelial cells, which may be the main mechanism underlying Mg-enhanced critical size bone defect repair when combined with DO, suggesting a great potential of Mg implants in reducing DO treatment time for clinical applications.

Locally Delivered Ascorbic Acid and β-Glycerophosphate Augment Local Bone Graft in a Murine Model of 2-Level Posterior Spinal Fusion.

Ascorbic acid is involved in collagen biosynthesis and upregulates alkaline phosphatase, potentially alleviating cell senescence and stimulating mesenchymal stem cell proliferation and differentiation into osteoblasts. We hypothesized locally delivered ascorbic acid and β-glycerophosphate act as a bone graft extender to increase the volume of new bone formed in a murine model of posterior lumbar fusion. Collagen sponges were used as delivery vehicles. Sponges were prepared with primary media alone or with the addition of ascorbic acid and β-glycerophosphate. Fresh morselized bone graft from 12 donor mice was used. Twenty-four healthy male C57BL/6 mice underwent an uninstrumented posterior L3-L5 lumbar fusion. One control group received morselized bone only. A second "sponge control" group received morselized bone with the control collagen sponge. The third group received morselized bone and a collagen sponge with ascorbic acid and β-glycerophosphate. Three months postoperatively, the lumbar spine underwent high-resolution micro-computed tomography for analysis of bone formation, density, and bridging fusion. Animals receiving ascorbic acid and β-glycerophosphate had a statistically significant increase in corrected bone volume compared with control and sponge groups, with a 56.3% and 25.4% increase, respectively. Mineralized bone fraction was statistically significantly decreased for animals in the ascorbic acid group compared with control and sponge groups. There was no significant difference in fusion rate between test groups. Locally delivered ascorbic acid and β-glycerophosphate in a murine model of posterior spinal fusion yielded statistically significant increases in new bone formation in the lumbar spine but statistically significant decreases in mineralized bone fraction. Differences in fusion rate were not statistically significant. This study provides early data suggesting that delivery of ascorbic acid to a spinal fusion site may be beneficial but does not yet establish an indication for clinical use. Further studies are needed to determine optimal dose and delivery of ascorbic acid.

Biodegradable magnesium combined with distraction osteogenesis synergistically stimulates bone tissue regeneration via CGRP-FAK-VEGF signaling axis

Critical size bone defects are frequently caused by accidental trauma, oncologic surgery, and infection. Distraction osteogenesis (DO) is a useful technique to promote the repair of critical size bone defects. However, DO is usually a lengthy treatment, therefore accompanied with increased risks of complications such as infections and delayed union. Here, we demonstrated that magnesium (Mg) nail implantation into the marrow cavity degraded gradually accompanied with about 4-fold increase of new bone formation and over 5-fold of new vessel formation as compared with DO alone group in the 5 mm femoral segmental defect rat model at 2 weeks after distraction. Mg nail upregulated the expression of calcitonin gene-related peptide (CGRP) in the new bone as compared with the DO alone group. We further revealed that blockade of the sensory nerve by overdose capsaicin blunted Mg nail enhanced critical size bone defect repair during the DO process. CGRP concentration-dependently promoted endothelial cell migration and tube formation. Meanwhile, CGRP promoted the phosphorylation of focal adhesion kinase (FAK) at Y397 site and elevated the expression of vascular endothelial growth factor A (VEGFA). Moreover, inhibitor/antagonist of CGRP receptor, FAK, and VEGF receptor blocked the Mg nail stimulated vessel and bone formation. We revealed, for the first time, a CGRP-FAK-VEGF signaling axis linking sensory nerve and endothelial cells, which may be the main mechanism underlying Mg-enhanced critical size bone defect repair when combined with DO, suggesting a great potential of Mg implants in reducing DO treatment time for clinical applications.

Vacuum plasma sprayed porous titanium coating on polyetheretherketone for ACDF improves the osteogenic ability: An in vitro and in vivo study.

Cervical degenerative disease is a common and frequently occurring disease, which seriously affects the health and quality of the life of patients worldwide. Anterior cervical decompression and interbody fusion is currently recognized as the gold standard for the treatment of degenerative cervical spondylosis. Polyetheretherketone (PEEK) has become the prevailing material for cervical fusion surgery. Although PEEK has excellent biocompatibility, it is difficult to form bone connection at its bone-implant interface due to its low surface hydrophilicity and conductivity. It is widely accepted that Ti has excellent osteogenic activity and biocompatibility. In this study, a Ti-PEEK composite cage was prepared by coating Ti on the surface of a PEEK cage using a vacuum plasma spraying technique to enhance the osteogenic property of PEEK. The Ti-PEEK samples were evaluated in terms of their in vitro cellular behaviors and in vivo osteointegration, and the results were compared to a pure PEEK substrate. The skeleton staining and MTS assay indicated that the MC3T3-E1 cells spread and grew well on the surface of Ti-PEEK cages. The osteogenic gene expression and western blot analysis of osteogenic protein showed upregulated bone-forming activity of MC3T3-E1 cells in Ti-PEEK cages. Furthermore, a significant increase in new bone formation was demonstrated on Ti-PEEK implants in comparison with PEEK implants at 12weeks in a sheep cervical spine fusion test. These results proved that the Ti-PEEK cage exhibited enhanced osseointegrative properties compared to the PEEK cage both in vitro and in vivo.

In Vivo Study for Clinical Application of Dental Stem Cell Therapy Incorporated with Dental Titanium Implants.

The aim of this study was to investigate the behavior of dental-derived human mesenchymal stem cells (d-hMSCs) in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo. d-hMSCs derived from alveolar bone were established and cultured on machined, sandblasted and acid-etched (SLA)-treated titanium discs with and without osteogenic induction medium. Their morphological and osteogenic potential was assessed by scanning electron microscopy (SEM) and real-time polymerase chain reaction (RT-PCR) via mixing of 5 × 106 of d-hMSCs with 1 mL of Metrigel and 20 μL of gel-cell mixture, which was dispensed into the defect followed by the placement of customized mini-implants (machined, SLA-treated implants) in New Zealand white rabbits. Following healing periods of 2 weeks and 12 weeks, the obtained samples in each group were analyzed radiographically, histomorphometrically and immunohistochemically. The quantitative change in osteogenic differentiation of d-hMSCs was identified according to the type of surface treatment. Radiographic analysis revealed that an increase in new bone formation was statistically significant in the d-hMSCs group. Histomorphometric analysis was in accordance with radiographic analysis, showing the significantly increased new bone formation in the d-hMSCs group regardless of time of sacrifice. Human nuclei A was identified near the area where d-hMSCs were implanted but the level of expression was found to be decreased as time passed. Within the limitations of the present study, in this animal model, the transplantation of d-hMSCs enhanced the new bone formation around an implant and the survival and function of the stem cells was experimentally proven up to 12 weeks post-sacrifice.

Gene activated scaffolds incorporating star-shaped polypeptide-pDNA nanomedicines accelerate bone tissue regeneration in vivo.

Increasingly, tissue engineering strategies such as the use of biomaterial scaffolds augmented with specific biological cues are being investigated to accelerate the regenerative process. For example, significant clinical challenges still exist in efficiently healing large bone defects which are above a critical size. Herein, we describe a cell-free, biocompatible and bioresorbable scaffold incorporating a novel star-polypeptide biomaterial as a gene vector. This gene-loaded scaffold can accelerate bone tissue repair in vivo in comparison to a scaffold alone at just four weeks post implantation in a critical sized bone defect. This is achieved via the in situ transfection of autologous host cells which migrate into the implanted collagen-based scaffold via gene-loaded, star-shaped poly(l-lysine) polypeptides (star-PLLs). In vitro, we demonstrate that star-PLL nanomaterials designed with 64 short poly(l-lysine) arms can be used to functionalise a range of collagen based scaffolds with a dual therapeutic cargo (pDual) of the bone-morphogenetic protein-2 plasmid (pBMP-2) and vascular endothelial growth factor plasmid (pVEGF). The versatility of this polymeric vector is highlighted in its ability to transfect Mesenchymal Stem Cells (MSCs) with both osteogenic and angiogenic transgenes in a 3D environment from a range of scaffolds with various macromolecular compositions. In vivo, we demonstrate that a bone-mimetic, collagen-hydroxyapatite scaffold functionalized with star-PLLs containing either 32- or 64- poly(l-lysine) arms can be used to successfully deliver this pDual cargo to autologous host cells. At the very early timepoint of just 4 weeks, we demonstrate the 64-star-PLL-pDual functionalised scaffold as a particularly efficient platform to accelerate bone tissue regeneration, with a 6-fold increase in new bone formation compared to a scaffold alone. Overall, this article describes for the first time the incorporation of novel star-polypeptide biomaterials carrying two therapeutic genes into a cell free scaffold which supports accelerated bone tissue formation in vivo.

Combined Delivery of Two Different Bioactive Factors Incorporated in Hydroxyapatite Microcarrier for Bone Regeneration.

The delivery of growth factors using a carrier system presents a promising and innovative tool in tissue engineering and dentistry today. Two of the foremost bioactive factors, bone morphogenetic protein-2 and vascular endothelial growth factor (VEGF), are widely applied using a ceramic scaffold. The aim of this study was to determine the use of hydroxyapatite microcarrier (MC) for dual delivery of osteogenic and angiogenic factors to accelerate hard tissue regeneration during the regenerative process. Two MCs of different sizes were fabricated by emulsification of gelatin and alpha-tricalcium phosphate (α-TCP). The experimental group was divided based on the combination of MC size and growth factors. For investigating the in vitro properties, rat mesenchymal stem cells (rMSCs) were harvested from bone marrow of the femur and tibia. For in vivo experiments, MC with/without growth factors was applied into the standardized, 5-mm diameter defects, which were made bilaterally on the parietal bone of the rat. The animals were allowed to heal for 8weeks, and samples were harvested and analyzed by micro-computed tomography and histology. Improved proliferation of rat mesenchymal stem cells was observed with VEGF loaded MC. For osteogenic differentiation, dual growth factors delivered by MC showed higher osteogenic gene expression, alkaline phosphatse production and calcium deposition. The in vivo results revealed statistically significant increase in new bone formation when dual growth factors were delivered by MC. Dual growth factors administered on a calcium phosphate matrix showed significantly enhanced osteogenic potential. We propose this system has potential clinical utility in providing solutions for craniofacial bone defects, with the added benefit of early availability.

Bone remodeling effects of Korean Red Ginseng extracts for dental implant applications

BackgroundThe formation of a nanotube layer on a titanium nanotube (N-Ti) plate facilitates an active reaction between bone cells and the material surface via efficient delivery of the surface materials of the dental implant into the tissues. Studies have reported that Korean Red Ginseng extracts (KRGEs) are involved in a variety of pharmacological activities: we investigated whether implantation with a KRGE-loaded N-Ti miniimplant affects osteogenesis and osseointegration. MethodsKRGE-loaded nanotubes were constructed by fabrication on pure Ti via anodization, and MC3T3-E1 cells were cultured on the N-Ti. N-Ti implants were subsequently placed on a rat's edentulous mandibular site. New bone formation and bone mineral density were measured to analyze osteogenesis and osseointegration. ResultsKRGE-loaded N-Ti significantly increased the proliferation and differentiation of MC3T3-E1 cells compared with cells on pure Ti without any KRGE loading. After 1–4 weeks, the periimplant tissue in the edentulous mandibular of the healed rat showed a remarkable increase in new bone formation and bone mineral density. In addition, high levels of the bone morphogenesis protein-2 and bone morphogenesis protein-7, besides collagen, were expressed in the periimplant tissues. ConclusionOur findings suggest that KRGE-induced osteogenesis and osseointegration around the miniimplant may facilitate the clinical application of dental implants.

Wharton's Jelly for Augmented Cleft Palate Repair in a Rat Critical-Size Alveolar Bone Defect Model.

Secondary alveolar bone grafts (ABGs) are the standard treatment for the alveolar defect in patients with cleft lip and palate (CLP), but remain invasive and have several disadvantages such as delayed timing of alveolar repair, donor-site complications, graft resorption, and need for multiple surgeries. Earlier management of the alveolar defect (primary ABG) would be ideal, but is limited by the minimal bony donor sites available in the infant. In this study we used a critical-size alveolar bone defect model in the rat to investigate the use of Wharton's Jelly (WJ), the stem cell-rich connective tissue matrix of the umbilical cord, to generate bone within the alveolar cleft. Human WJ was isolated and implanted into a critical-size alveolar bone defect model representative of secondary cleft ABG surgery in 10-11-week-old male Sprague-Dawley rats. The defects were monitored with CT imaging of living animals to evaluate bone regrowth and healing over 24 weeks, followed by histomorphometric evaluation at 24 weeks, after the last CT scan. CT data confirmed that the defect size was critical and did not lead to the union of the bones in the control animals (n = 12) for the entire duration of the study. New bone growth was stimulated leading to partial-to-full closure of the defect in the animals treated with WJ (n = 12). Twenty four weeks postoperatively, the percent increase in new bone formation in the WJ-treated group (156.58% ± 20.67%) was markedly higher than that in the control group (50.36% ± 21.07%) (p < 0.05). Histomorphometric data also revealed significantly greater new bone formation in WJ-treated versus control animals, confirming CT findings. qPCR analysis of human Alu elements was unable to detect any appreciable long-term persistence of human cells in the new bone, indicating that WJ may enhance bone growth by mediating osteoinduction in the host tissue, rather than through osteogenic differentiation of WJ-embedded cells. Impact statement In this study, Wharton's Jelly enhanced bone growth in a preclinical alveolar defect model, indicating its potential use as a natural adjunct in the repair of the alveolar cleft defect in patients with cleft lip and palate (CLP). The clinical success of this approach would represent a paradigm shift in the treatment of patients with CLP by reducing or eliminating the need for subsequent secondary alveolar bone graft and reducing their number of lifetime surgeries.

Randomized Controlled Clinical Trial of Nanostructured Carbonated Hydroxyapatite for Alveolar Bone Repair.

The properties of the biodegradation of bone substitutes in the dental socket after extraction is one of the goals of regenerative medicine. This double-blind, randomized, controlled clinical trial aimed to compare the effects of a new bioabsorbable nanostructured carbonated hydroxyapatite (CHA) with a commercially available bovine xenograft (Bio-Oss®) and clot (control group) in alveolar preservation. Thirty participants who required tooth extraction and implant placement were enrolled in this study. After 90 days, a sample of the grafted area was obtained for histological and histomorphometric evaluation and an implant was installed at the site. All surgical procedures were successfully carried out without complications and none of the patients were excluded. The samples revealed a statistically significant increase of new bone formation (NFB) in the CHA group compared with Bio-Oss® after 90 days from surgery (p < 0.05). However, the clot group presented no differences of NFB compared to CHA and Bio-Oss®. The CHA group presented less amount of reminiscent biomaterial compared to Bio-Oss®. Both biomaterials were considered osteoconductors, easy to handle, biocompatible, and suitable for alveolar filling. Nanostructured carbonated hydroxyapatite spheres promoted a higher biodegradation rate and is a promising biomaterial for alveolar socket preservation before implant treatment.

Tissue-engineered bone using mesenchymal stem cells versus conventional bone grafts in the regeneration of maxillary alveolar bone: A systematic review and meta-analysis.

The aim of this study was to compare tissue-engineered bone using mesenchymal stem cells (MSCs) and conventional bone grafts in terms of histomorphometric outcome, bone gained, and implant failure in the atrophic maxilla. A systematic review and meta-analysis of randomized clinical trials (RCTs) was conducted. An electronic search of several databases was performed. RCTs comparing tissue-engineered bone using MSCs to bone graft alone in rehabilitation of the atrophic maxilla were included. Outcome variables were a mean percentage of new bone formation, residual graft particles, and connective tissue. Bone gained and implant failure rate were also assessed. Risk ratio (RR) or standardized mean differences (SMD) were statistically analyzed. A total of 190 augmented sites enrolled in 12 RCTs were included in this study. Nine of the 12 RCTs included 153 maxillary sinuses that underwent sinus elevation, and three RCTs included 28 patients with bone grafting only. There was no significant increase in new bone formation between the two groups at 3 to 4 months (SMD = -0.232, CI, -0.659 to 0.195, low-quality evidence). However, at 6 months postgrafting, a statistically significant increase in new bone formation was found in favor of the tissue-engineered bone using the MSC group (SMD = 0.869%, CI, -1.98 to 9.310, moderate-quality evidence). No substantial difference was found between the two groups with respect to residual graft particles, connective tissue, bone gained, and implant failure rate (RR = 2.8, CI: 0.517 to 16.6, P = .226, very low-quality evidence). There is moderate- to very low-quality evidence supporting the use of tissue-engineered bone using MSC therapy in maxillary alveolar bone regeneration compared with conventional bone grafting without MSCs.

Ex vivo gene therapy using human bone marrow cells overexpressing BMP-2: "Next-day" gene therapy versus standard "two-step" approach.

Traditionally, ex vivo gene therapy involves a two-step approach, with culture expansion of cells prior to transduction and implantation. We have tried to simplify this strategy and eliminate the time and cost associated with culture expansion, by introducing "next-day" regional gene therapy using human bone marrow cells. The purpose of this study was to determine whether a lentiviral vector (LV) carrying the cDNA for BMP-2 can transduce freshly isolated human BM cells, leading to abundant BMP production and bone formation in vivo, and evaluate the in vivo osteoinductive potential of "next-day" gene therapy and the standard "two-step" tissue culture expansion approach. To this end, human bone marrow cells (HBMC) from patients undergoing total hip arthroplasty were harvested, transduced with a BMP-2-expressing LV either overnight ("next day" gene therapy; ND) or after culture expansion (cultured "two-step" approach; C) and then implanted into a rat critical-sized femoral defect. The animals were randomly assigned to one of the following groups: I; ND-HBMC transduced with LV-TSTA BMP-2, II; ND-HBMC transduced with LV-TSTA GFP, III; non-transduced ND-HBMC; IV; C-HBMC transduced with LV-TSTA BMP-2, V; C-HBMC transduced with LV-TSTA-GFP, VI; non-transduced C-HBMC. Treatment with either "next-day" or cultured HBMC demonstrated a significant increase in new bone formation compared with all negative control groups as seen in plain radiographs, microCT and histologic/histomorphometric analysis. At 12 weeks post-op, complete defect union on plain X-rays occurred in 7/14 animals in the ND-HBMC/BMP-2 group and 12/14 in the C-HBMC/BMP-2 treated rats. The two-step approach was associated with more consistent results, a higher union rate, and superiority with regards to all of the studied bone healing parameters. In this study we demonstrate proof of concept that BMP-2-transduced human bone marrow cells can be used to enhance bone healing in segmental bone defects, and that regional gene therapy using lentiviral transduction has the osteoinductive potential to heal large bone defects in clinical settings.

Evaluation of bone formation following the osteotome sinus floor elevation technique without grafting using cone beam computed tomography: a preliminary study

BackgroundOsteotome sinus floor elevation (OSFE) is used to increase the bone volume at the site of the maxillary sinus through the transalveolar approach. However, there is uncertainty regarding the necessity of the use of grafting material in order to maintain the space for new bone formation.ObjectiveThis study aimed to evaluate new bone formation 6 months after osteotome sinus floor elevation without grafting and to evaluate the correlations between residual bone height (RBH), implant protrusion length (IPL), and endo-sinus bone gain (ESBG).Material and methodsThirty-one implants (27 patients) from area 14–17 and 24–27 were included in the study. All implants had a history of OSFE without grafting, with cone beam computed tomography (CBCT) taken prior to the surgery. The clinical examination and radiographic examination using CBCT were performed again 6 months after implantation. The RBH, new bone level, ESBG, and IPL were measured. Paired sample t test and Pearson correlation were used to analyze the data.ResultsThe average RBH before surgery was 7.14 ± 1.07 mm and 6 months after surgery was 8.95 ± 1.17 mm. There was a significant increase in new bone formation in the 6 months following surgery (p < 0.05). The average ESBG and IPL were 1.8 ± 0.79 mm and 2.02 ± 0.73 mm, respectively. There was a significant positive correlation between the IPL and ESBG (p < 0.05) while there was a negative correlation between RBH and ESBG. This study also demonstrates a decrease in the percentage of bone formation in relation to IPL as the IPL increases. The survival rate of the implant was 100%.ConclusionSignificant new bone formation can be detected around the implant site 6 months after implantation using OSFE technique without grafting. There is a negative correlation between the RBH and ESBG. While IPL is correlated to ESBG and appears to be the influencing factors of bone formation changes in the maxillary sinus. The preliminary radiographic results suggest that OSFE technique without grafting in combination with optimal IPL can provide sufficient bone height for implant support with a 100% implant survival rate.

Osteocytic connexin 43 channels affect fracture healing.

The cross-talk between cells is very critical for moving forward fracture healing in an orderly manner. Connexin (Cx) 43-formed gap junctions and hemichannels mediate the communication between adjacent cells and cells and extracellular environment. Loss of Cx43 in osteoblasts/osteocytes results in delayed fracture healing. For investigating the role of two channels in osteocytes in bone repair, two transgenic mouse models with Cx43 dominant negative mutants driven by a 10 kb-DMP1 promoter were generated: R76W (gap junctions are blocked, whereas hemichannels are promoted) and Δ130-136 (both gap junctions and hemichannels are blocked). R76W mice (promotion of hemichannels) showed a significant increase of new bone formation, whereasdelayed osteoclastogenesis and healing was observed in Δ130-136 (impairment of gap junctions), but not in R76W mice (hemichannel promotion may recover the delay). These results suggest that gap junctions and hemichannels play some similar and cooperative roles in bone repair.

Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect.

Reconstruction of segmental bone defects poses a tremendous challenge for both orthopedic clinicians and scientists, since bone rehabilitation is requisite substantially and may be beyond the capacity of self-healing. Bone marrow mesenchymal stem cells (BMSCs) have been identified as an optimal progenitor cell source to facilitate bone repair since they have a higher ability for proliferation and are more easily accessible than mature osteoblastic cells. In spite of the potential of BMSCs in regeneration medicine, particularly for bone reconstruction, noteworthy limitations still remain in previous application of BMSCs, including the amount of cells that could be recruited, the compromised bone migration of grafted cells, reduced proliferation and osteoblastic differentiation ability, and likely tumorigenesis. Our current work demonstrates that BMSCs transplanted through the caudal vein can be mobilized by erythropoietin (EPO) to the bone defect area and participate in regeneration of new bone. Based on the histological analysis and micro-CT findings of this study, EPO can dramatically promote the effects on the osteogenesis and angiogenesis efficiency of BMSCs in vivo. Animals that underwent EPO+BMSC administration demonstrated a remarkable increase in new bone formation, tissue structure organization, new vessel density, callus formation, and bone mineral density (BMD) compared with the BMSCs alone and control groups. At the biomechanical level, we demonstrated that combing transplantation of EPO and BMSCs enhances bone defect reconstruction by increasing the strength of the diaphysis, making it less fragile. Therefore, combination therapy using EPO infusion and BMSC transplantation may be a new therapeutic strategy for the reconstruction of segmental bone defect.