Rapid Bone Formation Research Articles

Cellular Fragments as Biomaterial for Rapid In Vitro Bone-Like Tissue Synthesis.

Current stem cell-based techniques for bone-like tissue synthesis require at least two to three weeks. Therefore, novel techniques to promote rapid 3D bone-like tissue synthesis in vitro are still required. In this study, we explored the concept of using cell nanofragments as a substrate material to promote rapid bone formation in vitro. The methods for cell nanofragment fabrication were ultrasonication (30 s and 3 min), non-ionic detergent (triton 0.1% and 1%), or freeze-dried powder. The results showed that ultrasonication for 3 min allowed the fabrication of homogeneous nanofragments of less than 150 nm in length, which mineralized surprisingly in just one day, faster than the fragments obtained from all other methods. Further optimization of culture conditions indicated that a concentration of 10 mM or 100 mM of β-glycerophosphate enhanced, whereas fetal bovine serum (FBS) inhibited in a concentration-dependent manner, the mineralization of the cell nanofragments. Finally, a 3D collagen-cell nanofragment-mineral complex mimicking a bone-like structure was generated in just two days by combining the cell nanofragments in collagen gel. In conclusion, sonication for three min could be applied as a novel method to fabricate cell nanofragments of less than 150 nm in length, which can be used as a material for in vitro bone tissue engineering.

Efficacy of Sticky Bone as a Novel Autologous Graft for Mandibular Third Molar Extraction Socket Healing - An Evaluative Study.

Introduction:Recently, initiation and enhancement of extraction socket healing has been amplified by platelet concentrates, whereas the positive role of Sticky bone has been focused on maintaining alveolar bone dimensions. This study aimed to determine the effectiveness of Sticky Bone for socket grafting of mandibular third molars (M3Ms) in terms of soft- and hard-tissue healing.Materials and Methods:This split-mouth prospective trial constituted prophylactic removal of M3Ms with Sticky bone grafted in the study site as a primary predictor variable. Patients underwent 3 months of mandatory follow-up where pain, swelling, interincisal mouth opening, and gingival healing were measured on the 3rd, 7th, and 14th day using the Numeric Rating Scale, anatomic landmarks, steel metric ruler, and criteria given by Landry et al. respectively. Radiological healing was calculated based on the height of the socket, Kelly's Index, and histogram values immediately after the procedure at 1 week, 1 month, and 3 months, respectively. Statistical comparison was made using Paired t-test. P < 0.05 was considered significant.Results:Forty-seven patients (mean 26.83 ± 6.58 years) demonstrated significantly lesser pain, swelling, and better gingival healing at the study site on multiple periods of follow-up. Rapid bone formation with superior density, lesser alveolar resorption, earlier bone blending, and trabecular formation were noticed on the study site with a significant difference at all time intervals.Discussion:Sticky bone was chosen as the graft owing to advantages such as simple preparation, convenient handling characteristics, safety, evident postoperative patient comfort, better retention of the clot, enhanced soft-tissue healing, absence of infection, and decreased osseous deformation as compared to the control site. This study validated the role of Sticky bone as an indispensable component of regenerative therapy in the orofacial osseous tissues as it was an ideal biologic graft with fibrin rich structure.Conclusion:This study validated the role of Sticky bone as an indispensable component of regenerative therapy in the orofacial osseous tissues as it was an ideal biologic graft with fibrin rich structure.

Effect of titanium plate fixation on bone healing

Bone formation which is a process before bone remodeling in fracture healing process, was investigated in this study by fixing metallic plate after an artificially created defect in a rabbit femur. Although a complete bone remodeling takes about 6 weeks, present study was conducted by observing the condition of the bone within 3 weeks of healing period. An artificial defect was made in a rabbit femur and Ti-6Al-4V ELI (Ti-64) fixation plate was fixed with two screws on both ends while a defect without fixation was set as the control. After 3 weeks, the femur bone was harvested and evaluated with scanning electron microscopy, Vickers hardness test, and X-ray diffraction analysis. Ti-64 fixation showed rapid bone formation but external callus remaining on the defect area and its surrounding bone area. This bone callus may be replaced with healed bone with the passage of time. On the other hand, control showed incomplete bone formation and bone callus formed in the area without the defect, including further regions from the defect area. This may be affected by irregular load transmission and instability around the bone defect area. We conclude that, Ti-64 fixation shows better bone formation and bone hardness than the control.

Osteoconductive potential of a hydroxyapatite fiber material with magnesium: In vitro and in vivo studies.

Despite the benefits of hydroxyapatite fiber (HAf) as a synthetic bone substitute, materials capable of faster bone regeneration would be more preferable. In this study, effects of HAf with magnesium (Mg-HAf) on bone regeneration were evaluated. In vitro, levels of osteogenic genes were significantly higher in bone marrow cells cultured with Mg-HAf than in those cultured with HAf alone. Moreover, effects of HAf only (control) and 5.7 mol% Mg-HAf on the cranial bones of Japanese white rabbits were evaluated. MicroCT imaging and histology indicated significant differences between the control and Mg-HAf groups. Significantly higher new bone volumes and percentages were observed in the Mg-HAf group than in controls at 4 and 8 weeks (p<0.05); the newly formed bone was more mature in the Mg-HAf group than in controls. These results indicated that Mg-HAf can enhance osteogenic differentiationrelated gene expression and promote rapid bone formation and maturation.

Efficient in vivo bone formation by BMP-2 engineered human mesenchymal stem cells encapsulated in a projection stereolithographically fabricated hydrogel scaffold

BackgroundStem cell-based bone tissue engineering shows promise for bone repair but faces some challenges, such as insufficient osteogenesis and limited architecture flexibility of the cell-delivery scaffold.MethodsIn this study, we first used lentiviral constructs to transduce ex vivo human bone marrow-derived stem cells with human bone morphogenetic protein-2 (BMP-2) gene (BMP-hBMSCs). We then introduced these cells into a hydrogel scaffold using an advanced visible light-based projection stereolithography (VL-PSL) technology, which is compatible with concomitant cell encapsulation and amenable to computer-aided architectural design, to fabricate scaffolds fitting local physical and structural variations in different bones and defects.ResultsThe results showed that the BMP-hBMSCs encapsulated within the scaffolds had high viability with sustained BMP-2 gene expression and differentiated toward an osteogenic lineage without the supplement of additional BMP-2 protein. In vivo bone formation efficacy was further assessed using an intramuscular implantation model in severe combined immunodeficiency (SCID) mice. Microcomputed tomography (micro-CT) imaging indicated rapid bone formation by the BMP-hBMSC-laden constructs as early as 14 days post-implantation. Histological examination revealed a mature trabecular bone structure with considerable vascularization. Through tracking of the implanted cells, we also found that BMP-hBMSC were directly involved in the new bone formation.ConclusionsThe robust, self-driven osteogenic capability and computer-designed architecture of the construct developed in this study should have potential applications for customized clinical repair of large bone defects or non-unions.

Novel Strategy to Accelerate Bone Regeneration of Calcium Phosphate Cement by Incorporating 3D Plotted Poly(lactic-co-glycolic acid) Network and Bioactive Wollastonite.

Inefficient bone regeneration of self-hardening calcium phosphate cement (CPC) increases the demand for interconnected macropores and osteogenesis-stimulated substances. It remains a challenge to fabricate porous CPC with interconnected macropores while maintaining its advantages, such as plasticity. Herein, pastes containing CPC and wollastonite (WS) are infiltrated into a 3D plotted poly(lactic-co-glycolic acid) (PLGA) network to fabricate plastic CPC-based composite cement (PLGA/WS/CPC). The PLGA/WS/CPC recovers the plasticity of CPC after being heated above the glass transition temperature of PLGA. The presence of the 3D PLGA network significantly increases the flexibility of CPC in prophase and generates 3D interconnected macropores in situ upon its degradation. The addition of WS is helpful to improve the attachment, proliferation, and osteogenic differentiation of mouse bone marrow stromal cells in vitro. The in vivo experimental results indicate that PLGA/WS/CPC promotes rapid angiogenesis and bone formation. Therefore, the plastic CPC-based composite cement with a 3D PLGA network and wollastonite shows an obviously improved efficiency for repairing bone defects and is expected to facilitate the wider application of CPC in the clinic.

Evaluation of Tolerable Upper Intake Levels for Vitamin D in Children and Adolescents

In 2012, the European Food Safety Authority (EFSA) suggested a tolerable upper intake level (UL) for vitamin D at 100 µg/day for adults based on the risk of hypercalcaemia. EFSA concluded that consumption of up to 50 µg/day does not lead to hypercalcaemia in children and adolescents (10-17 years). Furthermore, EFSA stated that there is no reason to assume that children and adolescents in the phase of rapid bone formation and growth have a lower tolerance for vitamin D compared to adults, and a UL of 100 µg/day for adolescents aged 11-17 years and 50 µg/day in children 1-10 years, taking the smaller body size into account, was proposed.&#x0D; The Norwegian Food Safety Authority (NFSA) is currently revising the national regulation of maximum limits in food supplements (not yet harmonised in the European Economic Area (EEA)), including maximum limits for vitamin D. NFSA has therefore requested the Norwegian Scientific Committee for Food Safety (VKM) to evaluate the assumption in the EFSA opinion that children and adolescents can tolerate the same amount of vitamin D as adults due to rapid bone formation and growth. In children and adolescents with lower weight than adults, this assumption actually implies that adolescents can tolerate more vitamin D per kg body weight than adults. VKM is therefore requested to evaluate if there is scientific evidence that a UL at 50 µg/day for children (1-10 years) and 100 µg/day for adolescents (11-17 years) is safe.&#x0D; The present statement is prepared by members of the Panel on Nutrition, Dietetic Products and Novel Food and Allergy in VKM.&#x0D; Three literature searches were performed to find new relevant studies investigating high intakes of vitamin D in children and adolescents and the role of vitamin D in bone formation and growth.&#x0D; No studies supporting a higher tolerance to vitamin D in children and adolescents due to rapid bone formation and growth were retrieved in the literature search. Moreover, there is apparently no firm association between bone formation and vitamin D levels in children during their growth period into adolescence and adulthood. &#x0D; No studies investigating high intakes of vitamin D in children 1-10 years were found. Furthermore, no studies that have examined safety issues and/or adverse effects of vitamin D supplementation in doses above 50 µg/day in adolescents were identified. It can therefore not be concluded that the UL at 50 µg/day in children (1-10 years) and 100 µg/day in adolescents (11-17 years) is safe.&#x0D; In the 2002 report from European Scientific Committee on Food (SCF), a UL was set at 25 µg/day for children aged 2-10 years, and 50 µg/day for adolescents aged 11-17 years (corresponding to the UL for adults at that time). To the best of knowledge no serious, harmful effects have been reported for these doses of vitamin D.

The macroscopic and histomorphological properties of periosteal rib lesions and its relation with disease duration: evidence from the Luis Lopes Skeletal Collection (Lisbon, Portugal).

Periosteal new bone formation (PNBF) is a common finding in a large spectrum of diseases. In clinical practice, the morphology and location of periosteal lesions are frequently used to assist in the differential diagnosis of distinct bone conditions. Less commonly reported is the presence of PNBF on the ribs. This contrasts with the data retrieved from the study of skeletonized human remains that shows a high frequency of cases and a strong, albeit not specific, association between periosteal rib lesions and pulmonary conditions (e.g. tuberculosis). Despite that, an overall disagreement regarding the specificity and non-specificity of periosteal reactions exists in the study of dry bone remains. The insufficient number of clinical models exploring the morphology and the pathophysiology of PNBF's and the lack of systematic studies of pathological samples with a known diagnosis are claimed as major reasons for the disagreements. This study aimed to describe and compare the macroscopic and the histomorphologic appearance of periosteal rib lesions and to discuss their usefulness as diagnostic indicators. To pursue this goal, an assemblage of 13 rib samples (males=11, females=2, mean age-at-death=36.6years old) was collected from the Luis Lopes Skeletal Collection (Museu Nacional de História Natural e da Ciência, Universidade de Lisboa, Portugal). The assemblage belongs to individuals who died from pulmonary-TB (group 1), non-TB pulmonary infections (group 2) and other conditions (group 3). Prior to sample preparation, the ribs were visually inspected and the PNBF described according to its thickness, the degree of cortical integration and the type of new bone formed (e.g. woven, lamellar or both). After sampling, each bone sample was prepared for histological analysis under plane and polarized light microscopy. Macroscopically, the results showed no differences in the new bone composition between cause-of-death groups. Only slight differences in the degree of cortical integration, which was most frequently classified as mild to high in the pulmonary-TB group, were observed. Histologically, no distinguishing features were identified by pathological group. However, new bone microarchitectures were observed compatible with (1) acute, fast-growing processes (e.g. spiculated reactions), (2) long-standing processes with a rapid bone formation (e.g. appositional layering of bone) and/or (3) chronic, slow-growing processes (e.g. layers of compact lamellae). To some extent, these distinct rates of disease progression resonate with the cause-of-death listed for some individuals. Despite the small sample size, the results of this investigation are in agreement with previous studies, according to which the macroscopic and histological appearance of periosteal formations are not specific for a particular pathological conditions. Nevertheless, the results support the conclusion that the morphology of periosteal lesions is a good biological indicator for inferring the rate of progression and duration of pathological processes. This study provides important reference data regarding the histomorphology of periosteal lesions that can be used for comparative purposes, as well as to narrow down the differential diagnosis in unidentified skeletal remains.

Synergistic effect of alginate/BMP-2/Umbilical cord serum-coated on 3D-printed PCL biocomposite for mastoid obliteration model

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been used widely in bone tissue regeneration; however, the use of rhBMP‐2 can be limited clinically because extremely high doses can cause opposing effects on bone formation, such as high inflammation, edema, and even uncontrollable bone growth. To overcome the limitation of using BMP-2, we used an umbilical cord serum (UCS) that exhibits various growth factors (epidermal growth factor, transforming growth factor-β, nerve growth factor, etc.). To evaluate the effect of the UCS, we studied the synergistic effect of the composite scaffold using BMP-2/UCS/alginate coated on three-dimensional mesh-structured poly-ε-caprolactone (PCL), both in vitro and in vivo, using a rat mastoid obliteration model. The newly suggested biocomposite scaffold (BMP-2/UCS/alginate) demonstrates significantly rapid new bone formation (particularly, in the interstitial area of the scaffold) compared to those of two controls: PCL mesh structure coated with alginate, and BMP-2/alginate-coated PCL scaffold. Based on the in vitro and in vivo works, the present study demonstrates that the simultaneous use of low‐dose BMP‐2 and UCS increases osteogenesis significantly in a rat model compared to the control that uses only BMP‐2.

Application of Solution Plasma Surface Modification Technology to the Formation of Thin Hydroxyapatite Film on Titanium Implants

Hydroxyapatite (HA) coatings on titanium implants enhance rapid bone formation around the implant due to their osteoconductive property. The present study aimed to achieve a thin and uniform HA film coating on titanium implants by solution plasma treatment (SPT). Commercially pure titanium and porous titanium disks were employed. A pulse plasma generator was used on the disks for 30 min. Morphologic and crystallographic features of the deposited films were examined by scanning electron microscopy (SEM) and X-ray diffractometry (XRD). To evaluate the wettability of the disks, water droplet (20 µL) surfaces were measured using a contact angle analyzer. The initial attachment of osteoblast-like cells (MC3T3E1) on the titanium substrates before and after solution plasma treatment was evaluated by counting the number of attached cells after incubation for 4 h. After immersion in the mineralizing solution for up to seven days, no crystals were observed on the polished-Ti surface. A more uniform and dense precipitation of round and grown crystals with diameters of approximately 1–5 µm was observed on Ti-SPT. XRD clearly showed that the precipitated crystals on titanium disks were HA. The contact angle of the polished-Ti increased with time (θ = 37°–51°). The surface of the Ti-SPT remained hydrophilic (θ ˂ 5°) after up to 30 days of aging. The number of attached cells on the Ti-SPT after aging for 30 days remained above 85% of that on the Ti-SPT without aging. SPT in a mineralizing solution can be used to acquire a homogenous precipitation of HA on porous-surfaced titanium implants.

A laminin-derived functional peptide, PPFEGCIWN, promotes bone formation on sandblasted, large-grit, acid-etched titanium implant surfaces.

This study aimed to investigate the in vitro and in vivo bone-forming potential of a sandblasted, large-grit, acid-etched (SLA) titanium (Ti) surface treated with a laminin-derived functional peptide, PPFEGCIWN (DN3). Human osteoblast-like MG63 cells were cultured with SLA Ti discs untreated or treated with DN3 or a control scrambled peptide (SP). Cell adhesion, spreading, and viability on the discs were tested. Alkaline phosphatase gene expression and enzyme activity were also evaluated. Four DN3-coated SLA Ti implants and four untreated implants were placed into the tibiae of two rabbits (two implants/tibia). Ten days later, the bone-implant interfaces were subjected to histomorphometry to measure the bone response. The surface properties of the discs and implants were determined using scanning electron, widefield confocal, and confocal laser microscopy and x-ray photoelectron spectroscopy. The peptide-treated and untreated discs and implants were similar in terms of physical surface properties, but the peptide-treated surfaces had significantly higher nitrogen levels (P < .05). The DN3 peptide promoted cell adhesion, spreading, and alkaline phosphatase expression and enzyme activity (P < .05). Histomorphometry of the harvested implants showed rapid bone formation and affinity of the motif. This study suggests that treatment with the cell adhesion peptide DN3 promotes bone healing at the SLA Ti surface.

Evaluation of bone regeneration in periapical osseous defects with and without platelet rich plasma, combined calcium sulfate and autologous bone graft – A comparative study

BackgroundOsseous defects of the jaw occurs naturally by pathological conditions such as infections, tumors, cysts or iatrogenic causes induced during surgical treatment of preexisting periradicular bony pathologies. Management of these bone defects poses a great challenge for surgeons who are continually exploring ways to find new modalities to improvise bone substitutes. PurposeTo compare and evaluate bone regeneration with and without combining platelet rich plasma (PRP), calcium sulfate (CS) and autogenous bone graft in periapical defects of jaw. MethodsThe study is a randomized prospective comparative study, in which 20 patients were assigned, with 10 patients each forming the study and control groups. In the first group (study group) the bone defect was filled with PRP, calcium sulfate and autologous bone graft. In the second group (control group) defect was allowed to heal without PRP, calcium sulfate and autogenous bone graft. Digital orthopantogram (OPG) were taken to analyze the bone density and bone regeneration. The parameters used to analyze the radiographs included grey scale analysis, residual bone defect calculation in pixels both performed in Corel Photopaint X3® software and radiopaque scoring scale. Statistical analysis was carried out using Kolmogorov Smirnov test, Independent t-test and Anova test. ResultsThe mean bone defect density (BDD) measured using grey scale was significant in the study group during 5th, 13th and 20th week than the control group (P < 0.0001). The percentage bone formation analyzed using residual bone defect calculation revealed significantly higher size reduction in the study group than with the outcome obtained in the control group (P < 0.0001). The mean radiopaque score given by blinded observers also showed significance in the study group. ConclusionFrom the results of the study, it is clearly evident that radiographic bone density and rapid bone formation in the study group when compared to the control group. Thus the grouping of PRP, combined calcium sulfate with autologous bone graft proved to be a novel osteoinductive biomaterial.

The effects of NELL on corticotomy-assisted tooth movement and osteogenesis in a rat model.

Exogenous Nel-like molecule type 1 (NELL1) represents a potentially attractive clinical treatment option in the orthodontic and other settings because of its osteoinductive and vasculogenic properties. To explore effects of NELL1on corticotomy-assisted tooth movement and osteogenesis in a rat model. Thirty Sprague-Dawley rats were divided into 6 groups: Control, Sham, Tooth movement only, Vehicle, NELL1-LD (low-dose NELL), NELL1-HD (high-dose NELL). Human recombinant NELL1 protein was applied locally (Groups NELL1-LD and NELL1-HD) into buccal mucosa region of left first upper molar. Then the distance and velocity of tooth movement was measured, animals at 6 weeks after surgery were sacrificed, and was followed by computed tomography and histochemical staining. Both NELL1 groups had higher bone mineral density, greater tooth movement distance and velocity in comparison to the Vehicle group. Proximally and distally, periodontal ligament width was significantly increased in the NELL1-LD and NELL1-HD groups. Decortication enhances remodeling, however, rapid bone formation by high-dose NELL1 may affect bone absorption. Appropriate dose of NELL1 can be administrated to reduce the total time for tooth movement, and may shorten the treatment time in select populations.

Optimization of the configuration of porous bone scaffolds made of Polyamide/Hydroxyapatite composites using Selective Laser Sintering for tissue engineering applications

Numerous biomaterials are used to fabricate bone scaffolds to repair the bones subjected to trauma. The scaffolds are fabricated with interconnected pores with 40-70% porosity to facilitate the entry of the cells that ensures rapid bone formation. In addition, the interconnected pores also serve as a channel for the exchange of nutrients and waste materials. Rapid prototyping techniques use the CAD model of the scaffold to be fabricated which facilitates fabrication of components with complex architecture easily. This research deals with the design, fabrication and analysis of porous scaffold models with different configurations. Apart from the conventional pore geometry like cubical, spherical shaped pores, their shifted arrangements were also considered for this study. The minimum pore size used for the study is 400μm and the porosity ranges from 40-70%. Based on the results of finite element analysis, the best scaffold configuration is identified and was fabricated with different build orientation using Selective Laser Sintering (SLS) process with different mix of Polyamide and Hydroxyapatite. The fabricated test specimens were evaluated based on mechanical tests for its strength and in vitro studies with human osteosarcoma cell line for cell growth studies. The mechanical tests witnesses good physical properties than the earlier reported research. The suitability of the porous scaffolds for bone repair is also ensured using finite element analysis of a human femur bone under various physical activities.

Multifunctional Protein-Immobilized Plasma Polymer Films for Orthopedic Applications.

Osseointegration is essential for ensuring optimal functioning and longevity of orthopedic implants. In a significant number of patients, the body does not fully integrate with the orthopedic implant, which opens the potential for the formation of bacterial biofilms and adverse foreign body reactions. Protein-functionalization of the implant surfaces can reduce this potential by stimulating rapid cell attachment or bone formation. Ideally, a multifunctional protein surface should simultaneously stimulate cell attachment and bone formation for optimal osseointegration. In this study, we utilized primary mouse osteoblasts to examine the osteogenic potential of a multifunctional fusion protein, combining the fibronectin (FN) attachment and osteocalcin (OCN) bone signaling sequences, compared against that of the individual proteins. These three biomolecules were immobilized on radical-functionalized plasma polymer films (rPPFs) that covalently bond proteins through interactions with embedded radicals that migrate to the surface. The fusion protein was also compared to a coimmobilized ratio of FN:OCN prepared through a two-step sequential exposure to OCN solution followed by FN solution. The preparation and characterization overhead for the two protein surfaces was substantial when compared to the fusion protein functionalization process. Significantly greater osteoblast attachment and spreading were observed for the FN, FN:OCN, and fusion protein surfaces compared to titanium (p < 0.05), while the calcium deposition after 17 days showed a significant increase (p < 0.01) on the fusion protein surface alone. The greater osseointegration potential of the fusion protein surface compared to the single and coimmobilized protein surfaces is attributed to the homogeneous distribution of the attachment and signaling sequences. Overall, the fusion protein-coated rPPFs produced easily functionalizable and highly osteogenic surfaces with the potential to greatly improve the tissue integration of orthopedic implants.

Loading BMP-2 on nanostructured hydroxyapatite microspheres for rapid bone regeneration.

IntroductionTissue engineering is a promising strategy for bone regeneration in repairing massive bone defects. The surface morphology of implanted materials plays a key role in bone healing; these materials incorporate osteoinductive factors to improve the efficiency of bone regeneration.Materials and methodsIn the current study, nanostructured hydroxyapatite (nHAp) micro-spheres were prepared via a hydrothermal transformation method using calcium silicate (CS) microspheres as precursors; the CS microspheres were obtained by a spray-drying method. The nHAp microspheres constructed by the nano-whiskers significantly improved the ability of the microspheres to adsorb the bioactive protein (BMP-2) and reduce its initial burst release. To evaluate the in vivo bone regeneration of microspheres, both conventional hydroxyapatite (HAp) and nHAp microspheres were either loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) or not loaded with the protein; these microspheres were implanted in rat femoral bone defects for 4 and 8 weeks.Results and discussionThe results of our three-dimensional (3D) micro-computed tomography (CT) and histomorphometric observations showed that the combination of the nano-structured surface and rhBMP-2 obviously improved osteogenesis compared to conventional HAp microspheres loaded with rhBMP-2. Our results suggest that the nHAp microspheres with a nanostructured surface adsorb rhBMP-2 for rapid bone formation; they therefore show the potential to act as carriers in bone tissue regeneration.

Biomechanics of Immediate Postextraction Implant Osseointegration

The aim of this study was to gain insights into the biology and mechanics of immediate postextraction implant osseointegration. To mimic clinical practice, murine first molar extraction was followed by osteotomy site preparation, specifically in the palatal root socket. The osteotomy was positioned such that it removed periodontal ligament (PDL) only on the palatal aspect of the socket, leaving the buccal aspect undisturbed. This strategy created 2 distinct peri-implant environments: on the palatal aspect, the implant was in direct contact with bone, while on the buccal aspect, a PDL-filled gap existed between the implant and bone. Finite element modeling showed high strains on the palatal aspect, where bone was compressed by the implant. Osteocyte death and bone resorption predominated on the palatal aspect, leading to the loss of peri-implant bone. On the buccal aspect, where finite element modeling revealed low strains, there was minimal osteocyte death and robust peri-implant bone formation. Initially, the buccal aspect was filled with PDL remnants, which we found directly provided Wnt-responsive cells that were responsible for new bone formation and osseointegration. On the palatal aspect, which was devoid of PDL and Wnt-responsive cells, adding exogenous liposomal WNT3A created an osteogenic environment for rapid peri-implant bone formation. Thus, we conclude that low strain and high Wnt signaling favor osseointegration of immediate postextraction implants. The PDL harbors Wnt-responsive cells that are inherently osteogenic, and if the PDL tissue is healthy, it is reasonable to preserve this tissue during immediate implant placement.

Inhibition of bone resorption by bisphosphonates interferes with orthodontically induced midpalatal suture expansion in mice.

Craniofacial sutures are important growth sites for skull development and are sensitive to mechanical stress. In order to determine the role of bone resorption in stress-mediated sutural bone growth, midpalatal suture expansion was performed in mice receiving alendronate, an anti-resorptive bisphosphonate. The midpalatal sutures of 8-week-old C57BL/6 mice were expanded by orthodontic wires over the period of 2weeks. Mice with maxillary expansion without drug treatment as well as untreated animals served as controls. Skulls were analyzed with micro-computed tomography (micro-CT), immunohistochemistry and histology. Maxillary expansion in mice without drug treatment resulted in an increase of TRAP-positive osteoclasts. In contrast, no increase in osteoclasts was observed in expanded sutures of mice with bisphosphonate treatment. Double calcein labeling demonstrated rapid bone formation on the oral edges of the expanded sutures in mice without bisphosphonate treatment. Less bone formation was observed in bisphosphonate-treated mice after expansion. Histology revealed that the sutural architecture was reestablished in expanded sutures of mice without bisphosphonate treatment. In contrast, the sutural architecture was disorganized and the cartilage had an irregular form, following expansion in bisphosphonate-treated mice. Finally, micro-CT imaging demonstrated that the total amount of maxillary expansion was significantly lower in mice with bisphosphonate treatment as compared to those of mice without drug treatment. In conclusion, our results indicate that osteoclast-mediated bone resorption is needed for maxillary suture expansion and reorganization of sutural architecture. Orthodontic palatal expansion can be complicated in patients with inherited or drug-induced diseases of osteoclast dysfunction.

It Takes Two to Tango: Coupling of Angiogenesis and Osteogenesis for Bone Regeneration.

Bone regeneration is a complex process requiring highly orchestrated interactions between different cells and signals to form new mineralized tissue. Blood vessels serve as a structural template, around which bone development takes place, and also bring together the key elements for bone homeostasis into the osteogenic microenvironment, including minerals, growth factors and osteogenic progenitor cells. Vascular endothelial growth factor (VEGF) is the master regulator of vascular growth and it is required for effective coupling of angiogenesis and osteogenesis during both skeletal development and postnatal bone repair. Here, we will review the current state of knowledge on the molecular cross-talk between angiogenesis and osteogenesis. In particular, we will focus on the role of VEGF in coupling these two processes and how VEGF dose can control the outcome, addressing in particular: (1) the direct influence of VEGF on osteogenic differentiation of mesenchymal progenitors; (2) the angiocrine functions of endothelium to regulate osteoprogenitors; (3) the role of immune cells, e.g., myeloid cells and osteoclast precursors, recruited by VEGF to the osteogenic microenvironment. Finally, we will discuss emerging strategies, based on the current biological understanding, to ensure rapid vascularization and efficient bone formation in regenerative medicine.

Comparison of recombinant human bone morphogenetic protein-2-infused absorbable collagen sponge, recombinant human bone morphogenetic protein-2-coated tricalcium phosphate, and platelet-rich fibrin-mixed tricalcium phosphate for sinus augmentation in rabbits

Background/purposeNumerous grafting materials have been used in the bone regeneration of maxillary sinus to obtain a sufficient amount of new bone in implant dentistry. The objective of this study was to compare the potentials of Type I absorbable collagen sponge (ACS) impregnated with recombinant human bone morphogenetic protein (rhBMP)-2, rhBMP-2-coated tricalcium phosphate (TCP), platelet-rich fibrin-mixed TCP for enhancing bone regeneration in sinus augmentation in rabbits. Materials and methodsThe sinus defects were grafted with rhBMP-2+ACS (Group A), rhBMP-2-coated TCP (Group B), and platelet-rich fibrin-mixed TCP (Group C). The specimens underwent decalcification, and were stained for histomorphometric analysis. ResultsThere were no significant differences in inflammatory features among the groups 1-week postoperation. In a histomorphometric analysis, the new bone formation ratio showed significant differences between groups at 2 weeks. rhBMP-2+ACS showed a larger and more rapid bone formation area at 2 weeks than those of Groups B and C. ConclusionOur histological evaluation demonstrates that Type I ACS can be used as a carrier of rhBMP-2, and rhBMP-2+ACS showed rapid bone formation, remodeling, and calcification at Week 2 in rabbit.