Area Of New Bone Research Articles

Enhancing guided bone regeneration with cross-linked collagen-conjugated xenogeneic bone blocks and membrane fixation: A preclinical invivo study.

To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can enhance guided bone regeneration (GBR) in the overaugmented calvarial defect model. Four circular defects with a diameter of 8 mm were prepared in the calvarium of 13 rabbits. Defects were randomly assigned to receive one of the following treatments: (i) non-cross-linked (NCL) porcine-derived collagen-embedded bone block covered by a CM without fixation (NCL + unfix group); (ii) NCL bone block covered by CM with fixation using bone-tack (NCL + fix group); (iii) cross-linked (CL) porcine-derived collagen-embedded bone block covered by CM without fixation (CL + unfix group); and (iv) CL bone block covered by CM with fixation using bone-tack fixation (CL + fix group). The efficacy of GBR was assessed through histological and molecular analyses after 2 and 8 weeks. At 2 weeks, there were no significant differences in histologically measured areas of newly formed bone among the groups. At 8 weeks, however, the CL + fix group exhibited a larger area of new bone (5.08 ± 1.09 mm2, mean ± standard deviation) compared to the NCL + unfix (1.62 ± 0.42 mm2; p < .0083), NCL + fix (3.97 ± 1.39 mm2) and CL + unfix (2.55 ± 1.04 mm2) groups. Additionally, the expression levels of tumour necrosis factor-alpha, fibroblast growth factor-2, vascular endothelial growth factor, osteocalcin and calcitonin receptor were significantly higher in the CL + fix group compared to the other three groups (p < .0083). Cross-linked bone blocks stabilized with collagen membrane fixation can significantly enhance GBR.

Microwave assisted black phosphorus-based core-shell composites with synergistic antibacterial and osteogenic ability for bone tissue repair

In clinics, repairing bone tissue with methicillin-resistant Staphylococcus aureus (MRSA) infections and bone defects remains a remarkable challenge. This study designs new core-shell composites of PMP/PVA (Fe3O4@APNs based on magnesium phosphate cement/Fe3O4@APNs-VAN-PLGA microspheres-agarose hydrogel). With Fe3O4@APNs (Phytic acid dodecasodium exfoliated BPNs (APNs) modified with Fe3O4) as an enhanced microwave (MW) sensitizer, the PMP/PVA system exhibits outstanding MW thermal performance. Under MW irradiation, the PMP/PVA exerts dual antibacterial activity through the MW thermal effect (MTE, quickly increased to 68.7 ± 2.4 °C in 5 min at 2.45 GHz, 10 W/cm2) and MW-triggered chemotherapy (CTH, in vitro: 99.98 ± 0.02 % (MRSA), 99.43 ± 0.73 % (E. coli); in vivo: 99.98 ± 0.02 %), which possesses antibacterial ability in vitro and anti-infective effects in vivo with low toxicity and side effects. In addition, PMP/PVA possesses biodegradability with Ca2+, Mg2+, and PO43− released, which not only facilitates the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSC) in vitro but also promotes new bone formation for bone defect sites with chronic osteomyelitis in vivo (the implantations were gradually replaced with a large area of new bone without apparent cortical reactions). Therefore, PMP/PVA with dual antibacterial activity, osteogenic performance, and low toxicity ability can potentially repair bone tissue with MRSA infections and refractory bone defects. The proposed system is promising for bone tissue repair of chronic osteomyelitis with bone defects.

Enhanced immunomodulation and periodontal regeneration efficacy of subgingivally delivered progranulin-loaded hydrogel as an adjunct to non-surgical treatment for Class II furcation involvement in dogs.

To evaluate the effect of subgingival delivery of progranulin (PGRN)/gelatin methacryloyl (GelMA) complex as an adjunct to scaling and root planing (SRP) on an experimental periodontitis dog model with Class II furcation involvement (FI). A Class II FI model was established, and the defects were divided into four treatment groups: (a) no treatment (control); (b) SRP; (c) SRP + GelMA; (d) SRP + PGRN/GelMA. Eight weeks after treatment, periodontal parameters were recorded, gingival crevicular fluid and gingival tissue were collected for ELISA and RT-qPCR, respectively, and mandibular tissue blocks were collected for micro computed tomography (micro-CT) scanning and hematoxylin and eosin (H&E) staining. The SRP + PGRN/GelMA group showed significant improvement in all periodontal parameters compared with those in the other groups. The expression of markers related to M1 macrophage and Th17 cell significantly decreased, and the expression of markers related to M2 macrophage and Treg cell significantly increased in the SRP + PGRN/GelMA group compared with those in the other groups. The volume, quality and area of new bone and the length of new cementum in the root furcation defects of the PGRN/GelMA group were significantly increased compared to those in the other groups. Subgingival delivery of the PGRN/GelMA complex could be a promising non-surgical adjunctive therapy for anti-inflammation, immunomodulation and periodontal regeneration.

Tissue-engineered bone construct promotes early osseointegration of implants with low primary stability in oversized osteotomy

ObjectivesTo evaluate the histological parameters and bone mechanical properties around implants with low primary stability (PS) in grafted bone substitutes within an oversized osteotomy.Materials and methodsAn oversized osteotomy penetrating the double cortical bone layers was made on both femora of 24 New Zealand white rabbits. Bilaterally in the femur of all animals, 48 implants were installed, subdivided into four groups, corresponding to four prepared tissue-engineering bone complexes (TEBCs), which were placed between the implant surface and native bone wall: A: tricalcium phosphate β (TCP-β); B: autologous adipose derived-stem cells with TCP-β (ASCs/TCP-β); C: ASCs transfected with the enhanced-GFP gene with TCP-β (EGFP-ASCs/TCP-β); D: ASCs transfected with the BMP-2 gene with TCP-β (BMP2-ASCs/TCP-β). Trichrome fluorescent labeling was conducted. Animals were sacrificed after eight weeks. The trichromatic fluorescent labeling (%TFL), area of new bone (%NB), residual material (%RM), bone-implant contact (%BIC), and the removal torque force (RTF, N/cm) were assessed.ResultsASCs were successfully isolated from adipose tissue, and the primary ASCs were induced into osteogenic, chondrogenic, and adipogenic differentiation. The BMP-2 overexpression of ASCs sustained for ten days and greatly enhanced the expression of osteopontin (OPN). At eight weeks post-implantation, increased %NB and RTF were found in all groups. The most significant value of %TFL, %BIC and lowest %RM was detected in group D.ConclusionThe low PS implants osseointegrate with considerable new bone in grafted TEBCs within an oversized osteotomy. Applying BMP-2 overexpressing ASCs-based TEBC promoted earlier osseointegration and more solid bone mechanical properties on low PS implants. Bone graft offers a wedging effect for the implant with low PS at placement and promotes osteogenesis on their surface in the healing period.

Adrenomedullin has no effect on segmental bone defect healing but increases bone mineral density in rat model.

This study aimed to investigate the effect of adrenomedullin on the healing of the segmental bone defect in a rat model. Thirty-six Wistar rats were randomly divided into 6 groups based on follow-up periods and administered a dose of adrenomedullin hormone. In each group, bilaterally, a 2-mm bone defect was created at the diaphysis of the radius. Sodium chloride solution was administered to sham groups 3 times a week for 4 and 8 weeks intraperitoneally. Adrenomedullin was administered to the study groups 3 times a week: 15 μg-4 weeks, 15 μg-8 weeks, 30 μg-4 weeks, and 30 μg-8 weeks, respectively. After euthanasia, the segmental defects were evaluated by histomorphometric [new bone area (NBA)] and microtomographic [bone volume (BV), bone surface (BS), and bone mineral density (BMD)] analyses. Although the 4- and 8-week 15 μg administered study groups had higher NBA values than the other study and control groups, the histomorphometric analysis did not reveal any statistical difference between the control and study groups regarding NBA (P > .05). In microtomographic analysis, BV was higher in the 15 μg 4-week group than 30 μg 4-week group (296.9 vs. 208.5, P=.003), and BS was lower in the 30 μg 4-week group than in the 4-week control group (695.5 vs. 1334.7, P=.005), but overall, no significant difference was found between the control and study groups (P > .05). Despite these minor differences in histomorphometric and microtomographic criteria indicating new bone formation, the BMD values of the 15 μg 8-week study group showed a significant increase compared with the control group (P=.001, respectively). Adrenomedullin positively affected BMD at 15 μg, but this study could not show healing in the segmental defect site at different dose regimens. Further studies are needed to assess its effects on bone tissue trauma.

Evaluation of the time-dependent osteogenic activity of glycerol incorporated magnesium oxide nanoparticles in induced calvarial defects

IntroductionMagnesium-based biomaterials have been explored for their potential as bone healing materials, as a result of their outstanding biodegradability and biocompatibility. These characteristics make magnesium oxide nanoparticles (MgO NPs) a promising material for treating bone disorders. The purpose of this investigation is to assess the osteogenic activity of newly-developed locally administered glycerol-incorporated MgO NPs (GIMgO NPs) in rabbits’ calvarial defects. Materials and methodsCharacterization of GIMgO was done by X-ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). Bilateral calvarial defects were created in eighteen New Zealand Rabbits, of which they were divided into 3 groups with time points corresponding to 2, 4, and 6 weeks postoperatively (n = 6). One defect was implanted with absorbable gel foam impregnated with GIMgO NPs while the other was implanted with gel foam soaked with glycerol (the control). The defects were assessed using histological, Micro-Computed Tomography (Micro-CT), and histometric evaluation. ResultsThe characterization of the GIMgO nanogel revealed the presence of MgO NPs and glycerol as well as the formation of the crystalline phase of the MgO NPs within the nanogel sample. The histological and micro-CT analysis showed time-dependent improvement of healing activity in the calvarial defects implanted with GIMgO NPs when compared to the control. Furthermore, the histometric analysis demonstrated a marked increase in the total area of new bone, connective tissue, new bone area and volume in the GIMgO NPs implanted site. Statistically, the amount of new bone formation was more significant at 6 weeks than at 2 and 4 weeks postoperatively in the calvarial defects implanted with GIMgO NPs as compared to the control. ConclusionThe locally applied GIMgO NPs demonstrated efficacy in promoting bone formation, with more significant effects observed over an extended period. These findings suggest its suitability for clinical use as a therapeutic alternative to enhance bone healing.

Gallic acid-grafted chitosan antibacterial hydrogel incorporated with polydopamine-modified hydroxyapatite for enhancing bone healing.

An open critical-size bone defect is a major medical problem because of the difficulty in self-healing, leading to an increased risk of bacterial infection owing to wound exposure, resulting in treatment failure. Herein, a composite hydrogel was synthesized by chitosan, gallic acid, and hyaluronic acid, termed "CGH." Hydroxyapatite was modified with polydopamine (PDA@HAP) and introduced to CGH to obtain a mussel-inspired mineralized hydrogel (CGH/PDA@HAP). The CGH/PDA@HAP hydrogel exhibited excellent mechanical performances, including self-healing and injectable properties. Owing to its three-dimensional porous structure and polydopamine modifications, the cellular affinity of the hydrogel was enhanced. When adding PDA@HAP into CGH, Ca2+ and PO4 3- could release and then promoted differentiation of BMSCs into osteoblasts. Without any osteogenic agent or stem cells, the area of new bone at the site of defect was enhanced and the newly formed bone had a dense trabecular structure after implanting of the CGH/PDA@HAP hydrogel for 4 and 8 weeks. Moreover, the growth of Staphylococcus aureus and Escherichia coli was effectively inhibited through the grafting of gallic acid onto chitosan. Above, this study provides a reasonable alternative strategy to manage open bone defects.

Contact osteogenesis by biodegradable 3D-printed poly(lactide-co-trimethylene carbonate)

BackgroundTo support bone regeneration, 3D-printed templates function as temporary guides. The preferred materials are synthetic polymers, due to their ease of processing and biological inertness. Poly(lactide-co-trimethylene carbonate) (PLATMC) has good biological compatibility and currently used in soft tissue regeneration. The aim of this study was to evaluate the osteoconductivity of 3D-printed PLATMC templates for bone tissue engineering, in comparison with the widely used 3D-printed polycaprolactone (PCL) templates.MethodsThe printability and physical properties of 3D-printed templates were assessed, including wettability, tensile properties and the degradation profile. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were used to evaluate osteoconductivity and extracellular matrix secretion in vitro. In addition, 3D-printed templates were implanted in subcutaneous and calvarial bone defect models in rabbits.ResultsCompared to PCL, PLATMC exhibited greater wettability, strength, degradation, and promoted osteogenic differentiation of hBMSCs, with superior osteoconductivity. However, the higher ALP activity disclosed by PCL group at 7 and 21 days did not dictate better osteoconductivity. This was confirmed in vivo in the calvarial defect model, where PCL disclosed distant osteogenesis, while PLATMC disclosed greater areas of new bone and obvious contact osteogenesis on surface.ConclusionsThis study shows for the first time the contact osteogenesis formed on a degradable synthetic co-polymer. 3D-printed PLATMC templates disclosed unique contact osteogenesis and significant higher amount of new bone regeneration, thus could be used to advantage in bone tissue engineering.

Bone healing study of alendronate combined with enoxaparin sodium bone cement in rabbits with bone defects

BackgroundTo observe the effect of enoxaparin sodium-polymethyl methacrylate (ES-PMMA) bone cement supplemented with alendronate (AN) on bone repair of bone defects in New Zealand rabbits.MethodsTwenty-seven New Zealand rabbits were randomly divided into ES/AN, ES-PMMA and PMMA groups, with a total of 27 New Zealand rabbits. The drugs loaded in 40 g bone cement powder were as follows: ES/AN group 8000 AxaIU enoxaparin (ES) and 200 mg alendronate (AN), ES-PMMA group 8000 AxaIU enoxaparin (ES), PMMA group without drugs. A bone defect model with a length of 10 mm and a diameter of 5 mm was made from the left tibia of rabbits, and the prepared bone cement was placed in the tibia defect. At 4 weeks, 8 weeks and 12 weeks after the operation, 3 rabbits in each group were sacrificed, and left tibia samples were collected for histological scoring, HE staining and Masson staining. Bone mineral density and new bone volume were measured by imaging, and the related data were processed by one-way ANOVA and least significance difference (LSD) post hoc test.Results(1) Bone mineral density (BMD, mg/mm3) around the bone defect: at the 4th week, BMD in the ES/AN group was higher than that in the PMMA group; at the 8th week, the BMD in the ES/AN group was significantly higher than that in the other two groups; and at the 12th week, the BMD in the ES/AN group was significantly higher than that in the other two groups. (2) New bone volume (BV, mm3): at the 4th week, BV in the ES/AN group was significantly higher than that in the other two groups, BV in the ES/AN group was significantly higher than that in the other two groups at the 8th and 12th weeks, and BV in the ES-PMMA group was higher than that in the PMMA group. (3) Histological score: at the 4th and 8th weeks, the histological score of the ES/AN group was higher than that of the PMMA group, and at the 12th week, the histological score of the ES/AN group was higher than that of the other two groups. (4) Cortical bone thickness (μm): at the 4th, 8th and 12th weeks, the cortical bone thickness in the ES/AN group was higher than that in the other two groups, and the cortical bone thickness in the ES-PMMA group was higher than that in the PMMA group. (5) The percentage of mature area of new bone in the ES/AN group was higher than that in the other two groups at the 4th week, and at the 8th and 12th weeks, the percentage of mature area of new bone in the ES/AN group and ES-PMMA group was significantly higher than that in the PMMA group.Conclusion(1) Enoxaparin sodium bone cement supplemented with alendronate was superior to enoxaparin sodium bone cement and PMMA bone cement in promoting bone repair of tibial bone defects in New Zealand rabbits. (2) Enoxaparin sodium bone cement is superior to PMMA bone cement in promoting bone repair, showing a certain osteogenic potential.

Three-dimensionally printed biphasic calcium phosphate blocks with different pore diameters for regeneration in rabbit calvarial defects

BackgroundBiphasic calcium phosphate (BCP) is the most frequently used synthetic bone substitutes, which comprises a combination of hydroxyapatite (HA) and beta-tricalcium phosphate (b-TCP). Thanks to the recent advances in digital dentistry and three-dimensional (3D) printing technology, synthetic block bone substitutes can be customized to fit individual defect morphologies. The diameter of the pores can influence the rate of bone formation and material resorption. The aim of this study was to compare three-dimensionally printed biphasic calcium phosphate (BCP) block bone substitutes with different pore diameters (0.8-, 1.0-, and 1.2- mm) for use in the regeneration of rabbit calvarial defects.MethodsFour circular defects were formed on the calvaria of ten rabbits. Each defect was randomly allocated to one of the following study groups: (i) control group, (ii) 0.8-mm group, (iii) 1.0-mm group, and (iv) 1.2-mm group. All specimens were postoperatively harvested at 2 and 8 weeks, and radiographic and histomorphometric analyses were performed on the samples.ResultsHistologically, the BCP blocks remained unresorbed up to 8 weeks, and new bone formation occurred within the porous structures of the blocks. After the short healing period of 2 weeks, histomorphometric analysis indicated that new bone formation was significantly greater in the BCP groups compared with the control (p < 0.05). However, there were no significant differences between the groups with different pore diameters (p > 0.05). At 8 weeks, only the 1.0-mm group (3.42 ± 0.48 mm2, mean ± standard deviation) presented a significantly larger area of new bone compared with the control (2.26 ± 0.59 mm2) (p < 0.05). Among the BCP groups, the 1.0- and 1.2-mm groups exhibited significantly larger areas of new bone compared with the 0.8-mm group (3.42 ± 0.48 and 3.04 ± 0.66 vs 1.60 ± 0.70 mm2, respectively).ConclusionsWithin the limitations of this study, the BCP block bone substitutes can be applied to bone defects for successful bone regeneration. Future studies should investigate more-challenging defect configurations prior to considering clinical applications.

The influence of functional pinealectomy and exogenous melatonin application on healing of a burr hole in adult rat calvaria: a histological and immunohistochemical study.

Even today, repair of the cranial defects still represents a significant challenge in neurosurgery and various options have been used for their reconstruction to date. However, there are very few studies investigating the effects of exogenous administration of melatonin (MEL) as an agent that promotes bone regeneration. The goal of this study was to investigate the effects of functional pinealectomy (Px) and exogenous MEL administration on the bone repair properties and surrounding connective tissue alterations in a rat calvaria model. The total of 30 adult female Wistar-Albino rats was randomly divided into three groups (n = 10): control group (CO; 12 h light/12 h dark exposure), functional Px group (24 h light exposure, light-induced functional Px), and Px+MEL group (light-induced Px + MEL, 20 mg/kg/day for 12 weeks). Critical-sized burr-hole defects (diameter: 3.0 mm) were surgically created by a single operator in the calvarium of all rats, using an electric drill. Animals in Px+MEL group received MEL 20 mg/kg/day for 12 weeks. At the end of the study, bone healing and connective tissue alterations surrounding drilled defect area in the rat calvaria were determined in haematoxylin-eosin-stained and Mallory Azan slices applied in anti-bone sialoprotein. Image Pro Express 4.5 programme was used for histomorphometric calculation of areas of new bone and fibrotic tissue. Normality control was performed by Shapiro-Wilk test. Variance homogeneities were examined by Shapiro-Wilk and Levene tests; Tukey HSD test was used as a post hoc method since there was no homogeneity problem. All hypothesis tests were performed at the 0.05 significance level. Histological analysis showed that the bone repair process in the Px+MEL group was similar to that of the CO group, whereas the functional Px group showed a delay. Histomorphometrically, it was found that the Px group had the largest hole diameter and the most fibrotic scar area, although no binary statistical significance was found between the CO and Px+MEL groups (p = 0.910). In terms of vascularisation, it was observed that the most vascular structure was found in the Px+MEL group among the scar tissue and ossification areas, while the vascularisation was the least in the Px group (p < 0.001). Our findings revealed that bone repair process was impaired in functional Px group, but exogenous MEL replacement was able to restore this response. Thus, it is concluded that utilisation of MEL may improve the bone repair in calvarial defects.

Regeneration of Craniofacial Bone Induced by Periosteal Pumping.

A variety of surgical techniques and tissue engineering strategies utilizing osteogenic potential of the periosteum have been developed for the repair of extended bone deficiencies. The aim of the present study was to assess the impact of an alternating protocol of periosteal distraction osteogenesis (PDO) on bone regeneration in an intraoral model. Eight adult, male Beagle dogs were used for the study. Two distraction devices were placed on each side of the mandible. After a 7-day latency period, distraction devices in all animals were manipulated at the rate of 0.5 mm for a total of 8 days. The pumping protocol in two test groups proceeded twice daily by alternating activation with relaxation. In the periosteal pumping/distraction (PPDO) group, the distraction screws were activated two times (at 12 and 24 h) and then turned back (at 36 h), and in the periosteal pumping (PP) group repeatedly activated and turned back (at 12 h). In the PDO group, only activation was performed once daily (positive control). Devices were left inactivated in the negative control (NC) group. The samples were harvested after 8 weeks of consolidation period and investigated by micro-CT and histological analysis. New mature, lamellar bone was formed over the pristine bone in all groups. PPDO and PDO groups showed more new bone area (NBA) compared to the PP (p < 0.001 and p < 0.001, respectively) and to the NC group (p = 0.032 and p = 0.031, respectively). Furthermore, greater NBA was found in the PP group than the NC group (p = 0.006). PDO demonstrated higher relative connective tissue area than the PPDO group (p = 0.005) and lower relative new bone volume than the NC group (p = 0.025). Pumping protocol of periosteal distraction may successfully induce the endogenous regeneration of the mandibular bone in dogs. Impact Statement Repair of extended bone defects impose a significant challenge to oral and maxillofacial surgeons. In this article, a principle of distraction osteogenesis was applied to stimulate bone regeneration in the mandible. A periosteum-based regeneration approach may represent a valuable step toward creating a significant volume of hard and soft tissues, without need for autogenous bone harvesting or application of biomaterials.

ReGeneraTing agents as matrix-based therapy loaded on gelatin/beta tricalcium phosphate sponge for the treatment of class II furcation defects in vitro

ObjectivesThe experimental study was designed to evaluate the efficacy of gelatin sponge loaded with β tricalcium phosphate (β-TCP) with or without ReGeneraTing agent (RGTA) in the treatment of mandibular class II furcation defects in advanced periodontitis in vitro.Materials and methodsThree Egyptian Baladi dogs were included with average age 13–16 months and average body weight of 9–10 kg. Six critical size defects class II furcation defects were created in the mandible of each dog, three in the right and three in the left mandibular second, third, and fourth premolars. All defects were made in the same way by the same operator. The defects were treated either with RGTA loaded on gelatin/β-TCP sponge or placebo loaded on gelatin sponge/β-TCP in two groups (group I and group II) that blindly received one of the treatment modalities. Samples were collected from the surgical sites of the experimental defects after 12 weeks.ResultsHistologically and histomorphometrically: there was a statistically significant difference when group I was compared with group II regarding surface area of new bone formation.ConclusionRGTA loaded on gelatin/β-TCP sponge could be considered as a potentiating material for periodontal regeneration.

Delivery of MiR335-5p-Pendant Tetrahedron DNA Nanostructures Using an Injectable Heparin Lithium Hydrogel for Challenging Bone Defects in Steroid-Associated Osteonecrosis.

Corticosteroids-induced Dickkopf-1 (DKK1) upregulation and Wnt signaling inhibition result in bone metabolism disorder and steroid-associated osteonecrosis (SAON). Implanting biomaterials to regulate the Wnt pathway is a promising method to repair challenging bone defects associated with SAON. Here, tetrahedral DNA nanostructures (TDNs) are fabricated as gene carriers to deliver MiR335-5p, which targets DKK1 translation. Heparin lithium hydrogel (Li-hep-gel) is synthesized to act as a lithium and MiR@TDNs delivery agent. Finally, the repair effects on challenging bone defect in SAON using a MiR@TDNs/Li-hep-gel composite are assessed in vivo. The results reveal that MiR@TDNs are absorbed by bone mesenchymal stem cells (BMSCs) and increase cell viability and reduce apoptosis. Moreover, MiR@TDNs promote alkaline phosphatase expression and calcium nodular deposition, decrease lipid droplet expression of BMSCs, and improve vascular endothelial growth factor secretion and vascular-like structure formation in vitro. After MiR@TDNs/Li-hep-gel is implanted into the SAON model, the internal bone defect of osteonecrosis is repaired with a large area of new bone accompanied with neovascularization and reduced empty lacunae. In conclusion, MiR@TDNs/Li-hep-gel can provide dual delivery of lithium and MiR@TDNs, which synergistically upregulate the Wnt signaling pathway, enhancing bone regeneration in challenging bone defects, and can be potentially used in SAON repair.

Augmentation of implant surfaces with BMP-2 in a revision setting

AimsWe wanted to evaluate the effects of a bone anabolic agent (bone morphogenetic protein 2 (BMP-2)) on an anti-catabolic background (systemic or local zoledronate) on fixation of allografted revision implants.MethodsAn established allografted revision protocol was implemented bilaterally into the stifle joints of 24 canines. At revision surgery, each animal received one BMP-2 (5 µg) functionalized implant, and one raw implant. One group (12 animals) received bone graft impregnated with zoledronate (0.005 mg/ml) before impaction. The other group (12 animals) received untreated bone graft and systemic zoledronate (0.1 mg/kg) ten and 20 days after revision surgery. Animals were observed for an additional four weeks before euthanasia.ResultsNo difference was detected on mechanical implant fixation (load to failure, stiffness, energy) between local or systemic zoledronate. Addition of BMP-2 had no effect on implant fixation. In the histomorphometric evaluation, implants with local zoledronate had more area of new bone on the implant surface (53%, p = 0.025) and higher volume of allograft (65%, p = 0.007), whereas implants in animals with systemic zoledronate had the highest volume of new bone (34%, p = 0.003). Systemic zoledronate with BMP-2 decreased volume of allograft by 47% (p = 0.017).ConclusionLocal and systemic zoledronate treatment protects bone at different stages of maturity; local zoledronate protects the allograft from resorption and systemic zoledronate protects newly formed bone from resorption. BMP-2 in the dose evaluated with experimental revision implants was not beneficial, since it significantly increased allograft resorption without a significant compensating anabolic effect.Cite this article: Bone Joint Res 2021;10(8):488–497.

Accelerated Bone Induction of Adult Rat Compact Bone Plate Scratched by Ultrasonic Scaler Using Acidic Electrolyzed Water.

Fresh compact bone, the candidate graft material for bone regeneration, is usually grafted for horizontal bone augmentation. However, the dense calcified structure inhibits the release of growth factors and limits cellular and vascular perfusion. We aimed to create mechano-chemically altered dense skull bone by ultrasonic treatment, along with partial demineralization using commercially available acidic electrolyzed water (AEW). The parietal skull bone of an 11-month-old Wistar rat was exposed and continuously treated with a piezoelectric ultrasonic scaler tip for 1 min, using AEW (pH 2.3) or distilled water (DW, pH 5.6) as irrigants. Treated parietal bone was removed, cut into plates (5 × 5 × 1 mm3), grafted into the back subcutaneous tissues of syngeneic rats, and explanted at 1, 2, and 3 weeks. AEW bone showed an irregular surface, deep nano-microcracks, and decalcified areas. SEM-EDS revealed small amounts of residual calcium content in the AEW bone (0.03%) compared to the DW bone (0.86%). In the animal assay, the AEW bone induced bone at 2 weeks. Histomorphometric analysis showed that the area of new bone in the AEW bone at 2 and 3 weeks was significantly larger. This new combination technique of AEW-demineralization with ultrasonic treatment will improve the surface area and three-dimensional (3D) architecture of dense bone and accelerate new bone synthesis.

Comparison of the effectiveness of Ankaferd Blood Stopper® and Emdogain in periodontal regeneration.

The present study was performed to compare the effectiveness of Ankaferd Blood Stopper® (ABS) with enamel matrix derivatives (EMD) for treating fenestration defects in rats. Forty-eight male Wistar rats were randomly divided into six groups (each n=8). Fenestration defects were created in all rats, to which ABS, EMD, or saline (S) was then applied. The rats were grouped and sacrificed at one of two different time points, as follows: ABS-10-group, ABS-treatment/sacrifice on day 10; EMD-10-group, EMD-treatment/sacrifice on day 10; S-10-group, S-treatment/sacrifice on day 10; ABS-38-group, ABS-treatment/sacrifice on day 38; EMD-38-group, EMD-treatment/sacrifice on day 38; and S-38-group, S-treatment/sacrifice on day 38. Then, histomorphometric analysis including measurements of new bone area (NBA) and new bone ratio (NBR), and immunohistochemical analysis including the determination of osteopontin (OPN) and type-III-collagen (C-III) expression were performed. The NBA and NBR were significantly higher in the ABS-10-group and EMD-10-group compared to the S-10-group (p<.05), and in the EMD-38-group compared to the S-38-group (p<.05). The levels of C-III and OPN immunoreactivity were significantly higher in the ABS-10-group compared to the S-10-group (p<.017). The results of this study suggested that ABS can promote early periodontal regeneration, although its efficacy seems to decrease over time.

Is the Bacterial Cellulose Membrane Feasible for Osteopromotive Property?

Guided bone regeneration was studied to establish protocols and develop new biomaterials that revealed satisfactory results. The present study aimed to comparatively evaluate the efficiency of the bacterial cellulose membrane (Nanoskin®) and collagen membrane Bio-Gide® in the bone repair of 8-mm critical size defects in rat calvaria. Seventy-two adult male rats were divided into three experimental groups (n = 24): the CG—membrane-free control group (only blood clot, negative control), BG—porcine collagen membrane group (Bio-Guide®, positive control), and BC—bacterial cellulose membrane group (experimental group). The comparison periods were 7, 15, 30, and 60 days postoperatively. Histological, histometric, and immunohistochemical analyses were performed. The quantitative data were subjected to 2-way ANOVA and Tukey’s post-test, and p < 0.05 was considered significant. At 30 and 60 days postoperatively, the BG group showed more healing of the surgical wound than the other groups, with a high amount of newly formed bone (p < 0.001), while the BC group showed mature connective tissue filling the defect. The inflammatory cell count at postoperative days 7 and 15 was higher in the BC group than in the BG group (Tukey’s test, p = 0.006). At postoperative days 30 and 60, the area of new bone formed was greater in the BG group than in the other groups (p < 0.001). Immunohistochemical analysis showed moderate and intense immunolabeling of osteocalcin and osteopontin at postoperative day 60 in the BG and BC groups. Thus, despite the promising application of the BC membrane in soft-tissue repair, it did not induce bone repair in rat calvaria.

Enhanced new bone formation in canine maxilla by a graft of electrically polarized β-tricalcium phosphate.

We succeeded in the electrical polarization of β-tricalcium phosphate (β-TCP) granules and performed an unprecedented attempt to implant them into maxillary bone defects in canines to confirm their ability to facilitate new bone formation. Two holes were drilled into each maxilla half of a canine and filled with electrically polarized and nonpolarized β-TCP granules (grouping assignment was decided randomly). The implanted specimens were dissected en bloc and used for microcomputed tomography (μCT) observations and histological analyses 4 and 8 weeks after the operation. New bone ingrowth in the bone hole progressed over time from the superficial layer of the cortex toward the inner cancellous bone. The percentage area of new bone in the bone hole, as measured by μCT in the sagittal plane, was significantly larger after 4 and 8 weeks, and that measured by H&E-stained specimens in the transverse plane after 4 weeks was significantly larger in the polarized group than in the nonpolarized group. In addition to the structural stability and chemical characteristics of the β-TCP granules, electrical stimulation bears influence not indirectly but directly on osteogenic and vessel cells, which might work cooperatively for the early initiation of the bone formation process.

Lateral onlay grafting using different combinations of soft-type synthetic block grafts and resorbable collagen membranes: An experimental in vivo study.

To observe the sequential healing of lateral onlay grafts in terms of volumetric and histological changes when using different combinations of synthetic soft-type block bone and resorbable collagen membranes. A lateral onlay graft procedure was applied at the chronic narrow alveolar ridge of the mandible in 15 beagle dogs. The groups were allocated as follows: (a) empty control; (b) onlay graft using soft-type block bone 1 (hydroxyapatite [HA]: β-tricalcium phosphate [β-TCP]=15:85) and a non-cross-linked collagen membrane (MP-BG group); (c) onlay graft using soft-type block bone 2 (HA:β-TCP=60:40) and a non-cross-linked collagen membrane (OC-BG group); and (d) onlay graft using soft-type block bone 1 (HA:β-TCP=15:85) and a cross-linked collagen membrane (MP-CM group). Volumetric and histomorphometric analyses were performed at 4, 8 and 16weeks postoperatively. No clinical complications occurred in any of the groups. The OC-BG group showed significantly larger total augmented volumes than the control and MP-BG groups after 8 and 16weeks. The areas of new bone were significantly larger in the OC-BG group than the other groups at 16weeks. The horizontal thickness of the augmented ridge was significantly larger in the OC-BG group than in the control group at 16weeks. The OC-BG group showed superior volume maintenance and osteogenic potential for up to 16weeks compared to the other groups in an onlay graft model of the dog mandible despite the displacement of the bone graft.