Rate Of New Bone Formation Research Articles

Comparison of the osteogenic effects of demineralized dentin matrix and acellular dentin matrix.

This study aims to compare the osteogenic effects of implanting demineralized dentin matrix and acellular dentin matrix in bone defect areas. Demineralized dentin matrix and acellular dentin matrix were prepared. Twenty-four male SPF-grade SD rats were randomly divided into four groups: demineralized group (group A), acelluar group (group B), Bio-Oss bone powder group (group C), and blank control group (group D), with six rats in each group. All rats were subjected to general anesthesia to prepare bilateral femoral bone defects. Rats in groups A, B, and C were implanted with demineralized dentin matrix, acellular dentin matrix, and Bio-Oss bone powder at the bone defect area, respectively, while rats in group D were not implanted with any material. At 4 and 8 weeks after surgery, three rats were randomly executed in each group. The healing of the bone defect area was analyzed through gross observation. The concentrations of osteogenic indicators bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) were detected by serology. The distribution of high-density gray area (representing bone healing) in the bone defect area was observed by X-ray examination, and the formation of new bone was observed by histomorphology. The rate of new bone formation was calculated. At 4 and 8 weeks, the bone formation ability of group A was more active than that of the other groups; the concentrations of BMP-2 and ALP in group A were higher than those in the other groups, and the differences were statistically significant (P<0.05). At 8 weeks, the imaging observation showed that the high-density gray area in the bone defect of group A was evenly distributed. The histomorphological observation showed the regular arrangement of bone matrix in group A. The rate of new bone formation in group A was 28.51%±0.55% at 4 weeks and 32.57%±2.28% at 8 weeks, both of which were significantly higher than those in the other groups (P<0.05). Demineralized dentin matrix has better osteogenic potential than acellular dentin matrix.

Application of Three-Dimension Printing Nano-Carbonated-Hydroxylapatite to the Repair of Defects in Rabbit Bone.

Hydroxylapatite (HAp) is a biodegradable bone graft material with high biocompatibility. However, the clinical application of HAp has been limited due to the poor absorption rate in vivo. In this study, carbonated hydroxylapatite (CHAp) with a chemical composition similar to natural bone was synthesized. HAp and CHAp scaffolds were fabricated by 3D printing. Each material was designed by two types of scaffold model with a maximum width of 8 mm and a thickness of 2 mm, ie, structure I (round shape) and structure II (grid shape). Then, the HAp scaffolds were loaded with lutein. These scaffolds were implanted into the 8 mm bone defect on the top of the rabbit skull within 3 hours in the morning. The curative effects of the scaffolds were assessed two months after implantation. The 3D printed scaffolds did not cause severe inflammation or rejection after implantation. It showed that the porous structures allow bone cells to enter into the scaffolds. Furthermore, CHAp scaffolds were more biocompatible than HAp scaffolds, and showed a higher level of degradation and new bone formation after implantation. Structure II scaffolds with a smaller mineral content degraded faster than structure I, while structure I had better osteoconductive properties than structure II. Besides, the addition of lutein significantly enhanced the rate of new bone formation. The uniqueness of this study lies in the synthesis of 3D printed CHAp scaffolds and the implantation of CHAp in rabbit bone defects. The incorporation of suitable carbonate and lutein into HAp can enhance the osteoinductivity of the graft, and CHAp has a faster degradation rate in vivo, all of which provide a new reference for the research and application of apatite-based composites.

3D printed strontium-doped calcium phosphate ceramic scaffold enhances early angiogenesis and promotes bone repair through the regulation of macrophage polarization

The vascularization of bone repair materials is one of the key issues that urgently need to be addressed in the process of bone repair. The changes in macrophage phenotype and function play an important role in the process of vascularization, and endowing bone repair materials with immune regulatory characteristics to enhance angiogenesis is undoubtedly a new strategy to improve the effectiveness of bone repair. In order to improve the effect of tricalcium phosphate (TCP) on vascularization and bone repair, we doped strontium ions (Sr) into TCP (SrTCP) and prepared porous 3D printed SrTCP scaffolds using 3D printing technology, and studied the scaffold mediated macrophage polarization and subsequent vascularization and bone regeneration. The results of the interaction between the scaffold and macrophages showed that the SrTCP scaffold can promote the polarization of macrophages from M1 to M2 and secrete high concentrations of VEGF and PDGF-bb cytokines, which shows excellent angiogenic potential. When human umbilical vein endothelial cells (HUVECs) were co-cultured with macrophage-conditioned medium of SrTCP scaffold, HUVECs exhibited excellent early angiogenesis-promoting effects in terms of scratch healing, angiogenic gene expression, and in vitro tube formation performance. The results of in vivo bone repair experiments showed that the SrTCP scaffold formed a vascular network with high density and quantity in the bone defect area, which could increase the rate of new bone formation and advance the period of bone formation, and finally achieved a better bone repair effect. We observed a cascade effect in which Sr-doped SrTCP scaffold regulate macrophage polarization to enhance angiogenesis and promote bone repair, which may provide a new strategy for the repair of clinical bone defects.

Viability of Collagen Matrix Grafts Associated with Nanohydroxyapatite and Elastin in Bone Repair in the Experimental Condition of Ovariectomy.

Bone lesions have the capacity for regeneration under normal conditions of the bone metabolism process. However, due to the increasing incidence of major traumas and diseases that cause bone-mineral deficiency, such as osteoporosis, scaffolds are needed that can assist in the bone regeneration process. Currently, natural polymeric scaffolds and bioactive nanoparticles stand out. Therefore, the objective of the study was to evaluate the osteoregenerative potential in tibiae of healthy and ovariectomized rats using mineralized collagen and nanohydroxyapatite (nHA) scaffolds associated with elastin. The in-vivo experimental study was performed with 60 20-week-old Wistar rats, distributed into non-ovariectomized (NO) and ovariectomized (O) groups, as follows: Controls (G1-NO-C and G4-O-C); Collagen with nHA scaffold (G2-NO-MSH and G5-O-MSH); and Collagen with nHA and elastin scaffold (G3-NO-MSHC and G6-O-MSHC). The animals were euthanized 6 weeks after surgery and the samples were analyzed by macroscopy, radiology, and histomorphometry. ANOVA and Tukey tests were performed with a 95% CI and a significance index of p < 0.05. In the histological analyses, it was possible to observe new bone formed with an organized and compact morphology that was rich in osteocytes and with maturity characteristics. This is compatible with osteoconductivity in both matrices (MSH and MSHC) in rats with normal conditions of bone metabolism and with gonadal deficiency. Furthermore, they demonstrated superior osteogenic potential when compared to control groups. There was no significant difference in the rate of new bone formation between the scaffolds. Ovariectomy did not exacerbate the immune response but negatively influenced the bone-defect repair process.

Effect of Selective Serotonin Reuptake Inhibitor (Paroxetine) on Newly Formed Bone Volume: Real-Time In Vivo Micro–computed Tomographic Analysis

IntroductionSelective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression and anxiety. The purpose of this study was to assess in real time the effect of paroxetine, an SSRI, on newly formed bone volume (NFBV) in standardized calvarial defects (SCDs) in rats. MethodsFourteen Wistar albino female rats with a mean age of 7.5 months and a mean weight of 275 g were used. The animals were randomly divided into 2 groups. The experimental group was given paroxetine 8 weeks before the surgical procedure and throughout the experiment, and the control group was given a placebo 8 weeks before the surgical procedure and throughout the experiment. In each group, 14 SCDs measuring 4.6 mm in diameter were created on the parietal bone. In both groups, a Bio-Oss + collagen membrane was placed. All defects showed primary closure. The volume of the newly formed bone (NFBV) was measured using in vivo micro–computed tomographic imaging. Measurements were taken at days 0, 14, 28, 42, and 56 after surgery using real-time assessment with micro–computed tomographic imaging. ResultsThe mean NFBV was 17.12 ± 4.52 mm3 and 12.52 ± 4.78 mm3 for the control and experimental groups, respectively, at day 56. The differences between the 2 groups were statistically significant (P < .05) at all time intervals. ConclusionsParoxetine intake significantly reduced the amount of regenerated NFBV and the rate of new bone formation.

Revolutionizing bone regeneration: advanced biomaterials for healing compromised bone defects.

In this review, we explore the application of novel biomaterial-based therapies specifically targeted towards craniofacial bone defects. The repair and regeneration of critical sized bone defects in the craniofacial region requires the use of bioactive materials to stabilize and expedite the healing process. However, the existing clinical approaches face challenges in effectively treating complex craniofacial bone defects, including issues such as oxidative stress, inflammation, and soft tissue loss. Given that a significant portion of individuals affected by traumatic bone defects in the craniofacial area belong to the aging population, there is an urgent need for innovative biomaterials to address the declining rate of new bone formation associated with age-related changes in the skeletal system. This article emphasizes the importance of semiconductor industry-derived materials as a potential solution to combat oxidative stress and address the challenges associated with aging bone. Furthermore, we discuss various material and autologous treatment approaches, as well as in vitro and in vivo models used to investigate new therapeutic strategies in the context of craniofacial bone repair. By focusing on these aspects, we aim to shed light on the potential of advanced biomaterials to overcome the limitations of current treatments and pave the way for more effective and efficient therapeutic interventions for craniofacial bone defects.

The effects of boron trioxide on the structure and degradation behaviour of borosilicate bioactive glass

ABSTRACT Degradation behaviour of bioactive glass (bioglass) is one of the most important factors affecting bone repair, because an excellent and controllable degradation rate can match the rate of new bone formation. In this research, the derived borosilicate bioglasses based on the 6Na2O-8K2O-8MgO-22CaO-18B2O3-54SiO2-2P2O5 component were synthesized. The effects of B2O3 on the structure, degradation behaviour and cytocompatibility of borosilicate bioglasses were systematically studied. The results showed that with B2O3 addition, the network-forming units became diversified and part of BO4 units transformed into BO3 units. These factors weakened the chemical durability of borosilicate bioglass, thus accelerating the bioglass shedding and altering the ions release, especially B. This study provides a theoretical basis for designing borosilicate bioglass with adjustable degradation rate and ion release behaviour to meet the diverse needs of clinical bone repair.

Using Platelet-Rich Fibrin in Combination With Allograft Bone Particles Can Induce Bone Formation in Maxillary Sinus Augmentation

Sinus pneumatization secondary to posterior maxillary tooth extraction can hinder proper implant installation. Maxillary sinus floor augmentation is a surgical procedure that has been proposed to overcome this issue. The aim of this study was to evaluate and compare the histomorphometric outcomes of sinus floor elevation using allograft bone particles with or without platelet-rich fibrin (PRF). This randomized clinical trial included patients scheduled for maxillary sinus floor elevation in the Implant Department of Mashhad Dental School. Healthy adults with an edentulous maxilla and residual alveolar bone height of 3mm or less were eligible to participate and were randomly allocated to intervention (A) or control (B) groups. Bone biopsies were obtained 6months postoperatively. The predictor variable was using a PRF membrane for maxillary sinus augmentation. In group A, sinus floor elevation was performed using PRF combined with bone allografts, while in group B only allograft particles were used. The primary outcome variables were the recorded postoperative histologic parameters, as in the area of newly formed bone, new bone marrow, and residual graft particles (μm2). The secondary outcome variables were the radiographically measured postoperative bone height and width at the graft site. Age and sex. Independent sample t-test was employed to compare the postoperative histomorphometric parameters between groups A and B. P value ≤ .05 was considered statistically significant. A total of 20 patients (10 per group) completed the study. The mean rate of new bone formation was 43.25±5.22% in group A and 38.25±7.01% in group B. This difference was statistically insignificant (P=.087). The mean amount of newly formed bone marrow was significantly more in group A compared to group B (6.81±2.19% vs 10.23±4.49%; P=.044). The average amount of remaining particles was also significantly less in group A patients (9.35±3.43% vs 13.18±3.67%; P=.027). Incorporating PRF as an adjunctive grafting material results in fewer residual particles of allograft and in more bone marrow formation and may serve as a treatment option for developing the atrophic posterior maxilla.

CGF-HLC-I repaired the bone defect repair of the rabbits mandible through tight junction pathway.

Background: The human-like collagen I (HLC-I) combined concentrated growth factors was used to construct CGF-HLC-I composite biomaterials to repair the critical bone defect disease model of rabbit mandible. This study aimed to research the repair mechanism of CGF-HLC-I/Bio-Oss in rabbit mandibular critical bone defect, to provide a new treatment direction for clinical bone defect repair. Methods: The optimal concentration of HLC-I (0.75%) was selected in this study. Nine New Zealand white rabbits were randomly divided into 3 groups, normal control group, Bio-Gide/Bio-Oss and CGF-0.75%HLC-I/Bio-Oss group (n = 3, each group). CGF-0.75%HLC-I/Bio-Oss and Bio-Gide/Bio-Oss were implanted into rabbit mandibles, then X-ray, Micro-CT, HE and Masson staining, immunohistochemical staining and biomechanical testing were performed with the bone continuity or maturity at 4, 8 and 12 weeks after surgery. The repair mechanism was studied by bioinformatics experiments. Results: As the material degraded, the rate of new bone formation in the CGF-0.75% HLC-I/Bio-Oss group was better than that the control group by micro-CT. The biomechanical test showed that the compressive strength and elastic modulus of the CGF-0.75%HLC-I/Bio-Oss group were higher than those of the control group. HE and Masson staining showed that the bone continuity or maturity of the CGF-0.75%HLC-I/Bio-Oss group was better than that of the control group. Immunohistochemical staining showed significantly higher bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) in the CGF-0.75%HLC-I/Bio-Oss group than the control group at 8 and 12 W and the difference gradually decreased with time. There were 131 differentially expressed proteins (DEPs) in the Bio-Gide/Bio-Oss and CGF-0.75%HLC-I/Bio-Oss groups, containing 95 up-regulated proteins and 36 down-regulated proteins. KEGG database enrichment analysis showed actinin alpha 1 (ACTN1) and myosin heavy-Chain 9 (MYH9) are the main potential differential proteins related to osteogenesis, and they are enriched in the TJs pathway. Conclusion: CGF-0.75%HLC-I/Bio-Oss materials are good biomaterials for bone regeneration which have strong osteoinductive activity. CGF-0.75%HLC-I/Bio-Oss materials can promote new bone formation, providing new ideas for the application of bone tissue engineering scaffold materials in oral clinics.

In vivo comparison of the degradation and osteointegration properties of micro-arc oxidation-coated Mg-Sr and Mg-Ca alloy scaffolds.

Magnesium (Mg) alloy have biodegradation and mechanical properties that are similar to those of human bone, making it a promising candidate material for inclusion in implantable medical devices. The osteointegration effect of Mg alloy scaffolds with different corrosion rates were studied and evaluated in large bone defect models. Mg-Sr and Mg-Ca alloy scaffolds with a 20-μm Micro-arc oxidation (MAO) coating were used to repair critical bone defects for subsequent assessment of each alloy's degradation and osteointegration by X-ray, Micro-CT, fluorescence and histological examination. At 12 weeks post-implantation, each defect was found to be effectively reconstructed by either of the Mg alloys based on X-ray and Micro-CT images. The corrosion rate (CR) of each Mg alloy - as calculated based on micro-computed tomography information - demonstrated that the MAO coating could provide effective protection for only 4 weeks post-surgery. From weeks 8 to 12, the CR of the Mg-Ca alloy scaffold increased from 1.34±0.23mm/y to 1.57±0.16 mm/y. In contrast, the CR of the Mg-Sr alloy scaffold decreased from 0.58±0.14mm/y to 0.54±0.16mm/y. However, fluorescence and histological examination revealed more mature, closely and regularly arranged newborn osteocytes at the Mg-Ca scaffold-fracture interface e from weeks 8 to 12 after surgery. The Mg-Sr scaffold was more corrosion resistant and the Mg-Ca scaffold yielded a better overall repair, which indicates that the CR of magnesium alloys matches the rate of new bone formation and is the key to repair bone defects as a bone substitute.

Prefabrication technique by preserving a muscular pedicle from masseter muscle as an in vivo bioreactor for reconstruction of mandibular critical-sized bone defects in canine models.

In vivo bioreactors serve as regenerative niches that improve vascularization and regeneration of bone grafts. This study has evaluated the masseter muscle as a natural bioreactor for βTCP or PCL/βTCP scaffolds, in terms of bone regeneration. The effect of pedicle preservation, along with sole, or MSC- or rhBMP2-combined application of scaffolds, has also been studied. Twenty-four mongrel dogs were randomly placed in six groups, including βTCP, βTCP/rhBMP2, βTCP/MSCs, PCL/βTCP, PCL/βTCP/rhBMP2, and PCL/βTCP/MSCs. During the first surgery, the scaffolds were implanted into the masseter muscle for being prefabricated. After 2months, each group was divided into two subgroups prior to mandibular bone defect reconstruction; one with a preserved vascularized pedicle and one without. After 12 weeks, animals were euthanized, and new bone formation was evaluated using histological analysis. Histological analysis showed that all β-TCP scaffold groups had resulted in significantly greater rates of new bone formation, either with a pedicle surgical approach or non-pedicle surgical approach, comparing to their parallel groups of βTCP/PCL scaffolds (p ≤ .05). Pedicled β-TCP scaffold groups that were treated with either rhBMP2 (48.443% ± 0.250%) or MSCs (46.577% ± 0.601%) demonstrated the highest rates of new bone formation (p ≤ .05). Therefore, masseter muscle can be used as a local in vivo bioreactor with potential clinical advantages in reconstruction of human mandibular defects. In addition, scaffold composition, pedicle preservation, and treatment with MSCs or rhBMP2, influence new bone formation and scaffold degradation rates in the prefabrication technique.

Evaluation of the Efficacy of Mineralized Dentin Graft in the Treatment of Intraosseous Defects: An Experimental In Vivo Study.

Background and Objectives: Dentin grafts have osteoinductive and osteoconductive properties and are considered as an alternative to autogenous graft. This study evaluates the efficacy of autogenous mineralized dentin graft (AMDG) alone or with xenograft and compares it with those of various graft materials used in the treatment of intraosseous bone defects. Materials and Methods: The third incisor teeth of six sheep (2–3 years old) were extracted and AMDG was obtained. Six defects were prepared on each tibia of these six sheep: empty defect (group E); autogenous graft (group A), dentin graft (group D), xenograft (group X), autogenous + xenograft (group A + X) and dentin + xenograft (group D + X). Three sheep in each group were sacrificed in the post-operative 3rd and 6th week and the histologic analyses were performed. Results: The D and D + X groups showed histological features similar to the other groups in the 3rd and 6th weeks. No statistically significant difference was found regarding the rates of new bone formation between the D and D + X groups (p = 1.0) and the other groups at both time intervals (p > 0.05). Conclusions: Similar results observed in this study between groups A, D, X, A + X and D + X demonstrate that AMDG can be successfully used in the treatment of intraosseous bone defects. Further experimental and clinical studies are needed to be able to evaluate the effectiveness of dentin grafts in different types of indications.

The Ability and Mechanism of nHAC/CGF in Promoting Osteogenesis and Repairing Mandibular Defects.

Nano-hydroxyapatite/collagen (nHAC) is a new type of bone tissue engineering scaffold material. To speed up the new bone formation of nHAC, this study used concentrated growth factor (CGF) and nHAC in combination to repair rabbit mandibular defects. nHAC/CGF and nHAC were implanted into rabbit mandibles, and X-ray, Micro-CT, HE and Masson staining, immunohistochemical staining and biomechanical testing were performed at 8, 16 and 24 weeks after surgery. The results showed that as the material degraded, the rate of new bone formation in the nHAC/CGF group was better than that in the nHAC group. The results of the HE and Masson staining showed that the bone continuity or maturity of the nHAC/CGF group was better than that of the nHAC group. Immunohistochemical staining showed that OCN expression gradually increased with time. The nHAC/CGF group showed significantly higher BMP2 than the nHAC group at 8 weeks and the difference gradually decreased with time. The biomechanical test showed that the compressive strength and elastic modulus of the nHAC/CGF group were higher than those of the nHAC group. The results suggest that nHAC/CGF materials can promote new bone formation, providing new ideas for the application of bone tissue engineering scaffold materials in oral clinics.

Evaluation of osteogenic potential of Cissus quadrangularis on mandibular alveolar ridge distraction

BackgroundThis randomized clinical trial was designed to evaluate osteogenic potential of Cissus quadrangularis in alveolar distraction to facilitate implant installation.Material and methodsTwenty patients with atrophic ridge were treated by alveolar distraction. After completing distractor activation, patients were randomly divided into two equal groups according to administered drug (placebo and Cissus quadrangularis group). After a consolidation period, distractors were removed and implants were inserted. Clinical evaluation was done to assess wound healing, and distractor and implant stability. Histological evaluation was performed at time of implant insertion. Radiographic evaluation was performed to assess bone volume and density after distraction, as well as, density and bone loss around implant.ResultsRadiographic and histological results showed that bone formation and maturation of study group were faster than that of control group. There was a significant increased bone density in distracted area and around implant in study group than control group. A significant bone loss at end of consolidation period, and around implant at end of the study was reported in control group than study group.ConclusionCissus quadrangularis administration during the consolidation period is associated with increased osteogenic potential of distracted bone. The histological and radiographic findings of current study proved that Cissus quadrangularis not only enhances rate of new bone formation, but also bone density to withstand the biomechanical requirements of implant placement in a shorter time.Trial registrationThis study was retrospectively registered on www.ClinicalTrial.gov: NCT04669795-17\\12\\2020.

High toughness resorbable brushite-gypsum fiber-reinforced cements

The ideal bone substitute material should be mechanically strong, biocompatible with a resorption rate matching the rate of new bone formation. Brushite (dicalcium phosphate dihydrate) cement is a promising bone substitute material but with limited resorbability and mechanical properties. To improve the resorbability and mechanical performance of brushite cements, we incorporated gypsum (calcium sulfate dihydrate) and diazonium-treated polyglactin fibers which are well-known for their biocompatibility and bioresorbability. Here we show that by combining brushite and gypsum, we were able to fabricate biocompatible composite cements with high fracture toughness (0.47 MPa·m1/2) and a resorption rate that matched the rate of new bone formation. Adding functionalized polyglactin fibers to this composite cement further improved the fracture toughness up to 1.00 MPa·m1/2. XPS and SEM revealed that the improvement in fracture toughness is due to the strong interfacial bonding between the functionalized fibers and the cement matrix.This study shows that adding gypsum and functionalized polyglactin fibers to brushite cements results in composite biomaterials that combine high fracture toughness, resorbability, and biocompatibility, and have great potential for bone regeneration.

Design and characterization of injectable abalone shell/calcium sulfate bone cement scaffold for bone defect repair

• Abalone shell-derived bone cement was prepared according to the bionic principle. • The injectable and setting time of bone cement was extended to meet clinical injectable operation time. • The rate of degradation of bone cement was reduced to match the rate of new bone formation. • The cement composite exhibited the brilliant effects of bone regeneration. Abalone is a precious food and abalone shell can also be used as an ingredient of traditional Chinese medicine. However, large numbers of abalone shells are thrown away which results in resource waste and even environmental pollution. We have prepared an injectable natural bioactivity Abalone shell/calcium sulfate composite cement scaffold. Besides, we did a series of physiochemical, cellular, and animal tests. All results display that the scaffold owns good mechanical properties, predominant mineralization and controllable degradation properties. Also, the cement possesses excellent bioactivity, it can promote proliferation and differentiation of osteoblast to facilitate bone reconstruction. Thus, Abalone shell/Calcium sulfate composite cement scaffold would provide a new approach for both abalone high-value utilization and the clinical irregular bone defects rebuilding.

Multi-walled carbon nanotube/hydroxyapatite nanocomposite with leukocyte- and platelet-rich fibrin for bone regeneration in sheep model.

The aim of this study was to evaluate the effects of multi-walled carbon nanotubes/hydroxyapatite (MWCNT/HA) granules with or without leukocyte- and platelet-rich fibrin (L-PRF) on bone regeneration in cancellous bone of sheep model. Totally, 32 cylindrical holes were drilled in female sheep (n = 4) in the distal epiphysis and proximal metaphysis of right and left humerus and femur. The defects were randomly filled with (1) MWCNT/HA, (2) MWCNT/HA mixed with L-PRF, (3) L-PRF, and (4) left empty as control. After 8 weeks, defects were evaluated and compared radiographically using multi-slice computed tomographic (CT) scan and cone beam CT scans, histologically and histomorphometrically. The results showed that there was no significant inflammation (> 10%) or foreign body reaction around the granules. The new lamellar bone was regenerated around the MWCNT/HA nanocomposite granules. Addition of L-PRF to MWCNT/HA demonstrated significantly improvement of new bone formation, about 27.40 ± 1.08%, in comparison with the L-PRF alone, about (12.16 ± 1.46%) (P < 0.01). Also, the rate of new bone formation was significantly greater with the use of MWCNT/HA granules (24.59 ± 1.54%) compared to the control (10.36 ± 1.17%) (P < 0.01). Consequently, both biocompatibility and osteoconductivity of MWCNT/HA nanocomposite were demonstrated in the preclinical sheep model, and the use of L-PRF in combination with MWCNT/HA nanocomposite can improve bone regeneration.

In Vivo Evaluation of the Regenerative Capability of Glycylglycine Ethyl Ester-Substituted Polyphosphazene and Poly(lactic-co-glycolic acid) Blends: A Rabbit Critical-Sized Bone Defect Model.

In an effort to understand the biological capability of polyphosphazene-based polymers, three-dimensional biomimetic bone scaffolds were fabricated using the blends of poly[(glycine ethylglycinato)75(phenylphenoxy)25]phosphazene (PNGEGPhPh) and poly(lactic-co-glycolic acid) (PLGA), and an in vivo evaluation was performed in a rabbit critical-sized bone defect model. The matrices constructed from PNGEGPhPh-PLGA blends were surgically implanted into 15 mm critical-sized radial defects of the rabbits as structural templates for bone tissue regeneration. PLGA, which is the most commonly used synthetic bone graft substitute, was used as a control in this study. Radiological and histological analyses demonstrated that PNGEGPhPh-PLGA blends exhibited favorable in vivo biocompatibility and osteoconductivity, as the newly designed matrices allowed new bone formation to occur without adverse immunoreactions. The X-ray images of the blends showed higher levels of radiodensity than that of the pristine PLGA, indicating higher rates of new bone formation and regeneration. Micro-computed tomography quantification revealed that new bone volume fractions were significantly higher for the PNGEGPhPh-PLGA blends than for the PLGA controls after 4 weeks. The new bone volume increased linearly with increasing time points, with the new tissues observed throughout the defect area for the blend and only at the implant site's extremes for the PLGA control. Histologically, the polyphosphazene system appeared to show tissue responses and bone ingrowths superior to PLGA. By the end of the study, the defects with PNGEGPhPh-PLGA scaffolds exhibited evidence of effective bone tissue ingrowth and minimal inflammatory responses. Thus, polyphosphazene-containing biomaterials have excellent translational potential for use in bone regenerative engineering applications.

The elevated level of IL-1α in the bone marrow of aged mice leads to MSC senescence partly by down-regulating Bmi-1.

Osteoporosis is becoming increasingly prevalent with individual aging. Recent studies found that bone marrow mesenchymal stem cells (MSCs) undergo senescence along with the progression of age-related osteoporosis, leading to a decreased rate of new bone formation and fracture repair. The underlying mechanism of MSC senescence in the aged bone marrow has not been clarified yet. Here we found that MSCs from aged mice (12-month-old, O-MSCs) exhibited apparent senescent phenotypes compared with those from young controls (2-month-old, Y-MSCs), including lower proliferation rate, impaired self-renewal capacity, increased p16Ink4a expression and shifted differentiation balance to favor adipocytes over osteoblasts. Bmi-1, one of the main factors that regulate stem cell self-renewal, is dramatically decreased in O-MSCs. Knocking-down of Bmi-1 in Y-MSCs lead to cellular senescence, while over-expression of it rejuvenated O-MSCs. We further showed that the level of IL-1α is much higher in the bone marrow fluid of aged mice, which significantly inhibited Bmi-1 expression in MSCs. Our present study indicated that IL-1α, a key component of the senescence-associated secretory phenotype (SASP), is elevated in the aged bone marrow microenvironment, leading to decreased Bmi-1 expression in MSCs and consequently, MSC senescence.

Influence of different carrier materials on biphasic calcium phosphate induced bone regeneration.

Biphasic calcium phosphate (BCP) is a bioceramic material successfully used in alloplastic bone augmentation. Despite many advantages, a disadvantage of BCP seems to be a difficult application and position instability. The aim of this study was to determine how different carrier materials influence BCP-induced quantitative and qualitative bone regeneration. A total of 70 critical size defects were set in the frontal bone of 14 domestic pigs (5 each) and filled randomly with either BCP alone (BCP), BCP in combination with nano-hydroxyapatite (BCP + NHA), BCP embedded in native porcine type I/III collagen blocks (BCP + C), autologous bone (AB), or were left empty (ED). Specimens were harvested after 4 and 8 weeks and were evaluated histologically as well as histomorphometrically. Significantly lowest rate of new bone formation was found in ED (p = < 0.001) and BCP + NHA groups (p = 0.05). After 8 weeks, the highest percentage of new bone formation was observed in the BCP + C group. Fibrous matrix was detected highest in BCP alone. The lowest residual bone substitute material was found in BCP + C after 8 weeks. BCP-induced bone regeneration is indeed affected by different carrier types. Surface morphology and bioactive characteristics influence osseointegration and new bone formation in vivo. The combination of type I/III collagen seems most suitable for qualitative and quantitative bone regeneration. Stabilization of granular bone substitutes using type I/III collagen might be an alternative to granulates alone, indicating excellent volume stability, satisfactory plasticity, and easy application.