The Clinical Efficacy and Safety of ErhBMP-2/BioCaP/ß-TCP as a Novel Bone Substitute Using the Tooth-Extraction-Socket-Healing Model: A Proof-of-Concept Randomized Controlled Trial.

AIM: This first randomized controlled trial in humans aimed to assess the efficacy and safety of low-dosage Escherichia coli-derived recombinant human bone morphogenetic protein 2 (ErhBMP-2)-incorporated biomimetic calcium phosphate coating-functionalized ß-TCP (ErhBMP-2/BioCaP/ß-TCP) as a novel bone substitute using the tooth-extraction-socket-healing model. MATERIALS AND METHODS: Forty patients requiring dental implants after single-root tooth extraction were enrolled in this study and randomly assigned into three groups: ErhBMP-2/BioCaP/ß-TCP (N = 15), ß-TCP (N = 15) and natural healing (N = 10). New bone volume density from histomorphometric analyses was evaluated 6 weeks post-operatively as the primary outcome, and other histomorphometric analyses, alveolar bone and soft-tissue changes were the secondary outcomes. Safety parameters included adverse events, soft-tissue healing, oral health impact profile, serum BMP-2 concentrations and other laboratory tests. RESULTS: The findings revealed a significant increase in new bone volume density in patients treated with ErhBMP-2/BioCaP/ß-TCP compared to those receiving ß-TCP alone. The required bone augmentation procedures during implant placement surgery in the ErhBMP-2/BioCaP/ß-TCP group were significantly less than in the natural healing group. There were no significant differences in safety parameters among the three groups. CONCLUSION: This clinical trial primarily proved the safety and efficacy of ErhBMP-2/BioCaP/ß-TCP as a promising bone substitute.

Paradox: Curcumin, a Natural Antioxidant, Suppresses Osteosarcoma Cells via Excessive Reactive Oxygen Species.

Osteosarcoma (OS) is an aggressive tumor with a rare incidence. Extended surgical resections are the prevalent treatment for OS, which may cause critical-size bone defects. These bone defects lead to dysfunction, weakening the post-surgical quality of patients' life. Hence, an ideal therapeutic agent for OS should simultaneously possess anti-cancer and bone repair capacities. Curcumin (CUR) has been reported in OS therapy and bone regeneration. However, it is not clear how CUR suppresses OS development. Conventionally, CUR is considered a natural antioxidant in line with its capacity to promote the nuclear translocation of a nuclear transcription factor, nuclear factor erythroid 2 (NRF2). After nuclear translocation, NRF2 can activate the transcription of some antioxidases, thereby circumventing excess reactive oxygen species (ROS) that are deleterious to cells. Intriguingly, this research demonstrated that, in vitro, 10 and 20 µM CUR increased the intracellular ROS in MG-63 cells, damaged cells' DNA, and finally caused apoptosis of MG-63 cells, although increased NRF2 protein level and the expression of NRF2-regulated antioxidase genes were identified in those two groups.

Influence of radiotherapy on dental implants placed in individuals before diagnosed with head and neck cancer: focus on implant-bed-specific radiation dosage.

OBJECTIVES: The influence of radiotherapy on implants placed before diagnosed as head and neck cancer (HNC) is a potentially informative but poorly explored topic. The aims of this study were to investigate the influence of implant-bed-specific radiation dose on dental implants and to evaluate the impact of these implants on radiation dosimetry. MATERIAL AND METHODS: We conducted a retrospective study with 58 irradiated patients that received dental implant restorations before undergoing radiation treatment for HNC. The radiological success rate and the peri-implant bone resorption values were measured radiographically at 1 and 3 years after radiotherapy. Patients with no implants matching tumor site and stage served as a control group (n = 58). RESULTS: The median implant-bed-specific radiation dose was 40.3 Gy, which was significantly lower than tumor bed 62.4 Gy. An implant-bed-specific radiation dose higher than 40.0 Gy showed a significantly decreased radiologic success rate when compared to lower doses. Finally, evaluation of the radiation treatment plans revealed similar radiation hot spots in the test group of patients with implants and those of the control group. CONCLUSION: Our study confirms that radiotherapy negatively worsens peri-implant bone resorption, especially for implant-bed-specific dose more than 40 Gy, and the presence of implants within the radiation fields does not alter radiation dosimetry. The findings could be clinically informative to both surgeons and radio-oncologists. CLINICAL RELEVANCE: The interactions between radiotherapy and implants placed prior to radiotherapy treatment remain a largely unexplored topic. Based on the analysis of 3-dimensional modulated radiation plans, this study demonstrates the impact of implant-bed-specific radiation dose on marginal bone resorption of implants placed pre-radiation and considers the influence of these implants on radiation dosimetry. REGISTRATION NUMBER: CHICTR2100051923: ( http://www.chictr.org.cn/usercenter.aspx ).

Plaque removal efficacy of a compacted dual-head power toothbrush: A split-mouth randomized clinical trial.

PURPOSE: To evaluate the plaque removal efficacy of a compacted dual-head power toothbrush (DH) in comparison with a single-head power toothbrush (SH). METHODS: 24 healthy university students were included in this split-mouth and single-center clinical trial. The DH and SH were randomly assigned to brush the left/right half mouth in the first visit. Testing time points were 30 and 60 seconds. Additionally, 15 and 45 seconds were set for the DH period. The overall, buccal, lingual, gingival marginal, and proximal plaque scores at different time points were recorded and determined by Rustogi Modification of the Navy Plaque Index. To avoid the influence of the right handedness, subjects were brushed in the second visit after 4 weeks, and the SH and the DH were assigned to the right/left half mouth in an opposite period to that of the first visit. RESULTS: 21 participants completed this study. Overall plaque score reductions of the SH and DH were 29% and 59% (P< 0.05) at 30 seconds, and the reductions were 47% and 77% respectively (P< 0.05) at 60 seconds. Using the DH for 45 seconds reduced significantly more overall, buccal, lingual, and gingival marginal plaque than that of using SH for 60 seconds (P< 0.05). The SH reduced plaque scores significantly less in the right and lower dentitions than left and upper dentitions respectively, while DH reduced comparable plaque scores between these dentitions. The DH is more effective in removing overall, buccal, lingual, gingival marginal, and proximal plaque in healthy university students than the SH, meanwhile DH showed comparable overall plaque reduction rates between different regions of the dentitions. CLINICAL SIGNIFICANCE: This compact dual-head power toothbrush provides a new option to carry out daily plaque control effectively.

Identification and Description of a New Pathogen Causing Flower Dry Rot on Passiflora edulis in China.

Passiflora edulis Sims (passion fruit) is an economically important fruit crop. However, a new flower dry rot has occurred in orchards located in Zhanjiang, China, and has led to serious production loss. Its disease incidence is approximately 30 to 40%. A total of 221 isolates of Fusarium sp. were obtained from samples of three types of symptomatic flowers. Three representative single-spore isolates (PaB-1, PaB-2, and PaB-3) from each type were used for pathogenicity tests, multilocus phylogenetic analyses, and morphological descriptions. Pathogenicity tests of buds of 5-month-old P. edulis plants showed symptoms similar to those observed in nature, and Koch's postulates were achieved. By comparing 36 typical species from the FUSARIUM-ID database, multilocus phylogenetic analyses showed that the sequences of TEF1, RPB2, and ITS of these isolates belong to the Incarnatum clade of the F. incarnatum-equiseti species complex (FIESC-17-a) with an independent branch. Therefore, the pathogenic isolates were identified as F. pernambucanum (FIESC-17-a). Moreover, in this study, the conidial anastomosis tubes were first observed in the FIESC. This is the first report of flower dry rot on P. edulis caused by F. pernambucanum. Further studies should be performed to determine effective disease management strategies.

Vertical bone augmentation with simultaneous implantation using deproteinized bovine bone block functionalized with a slow delivery of BMP-2.

OBJECTIVE: We hypothesized that a biomimetic calcium phosphate (CaP) coating which incorporates morphogenetic protein 2 (BMP-2) on the deproteinized bovine bone (DBB) blocks could be used to enhance the vertical alveolar ridge augmentation for the one-stage onlay surgery with simultaneous implants insertion. We aimed to test this hypothesis in vivo. MATERIAL AND METHODS: Beagles dogs were used for the study (n = 6 specimens per group). One month after building the edentulous animal model, 4 mm vertical alveolar bone loss were surgically created and four groups of blocks (W × L × H: 7 mm × 10 mm × 4 mm) were randomly fixed onto the reduced alveolar ridge by implants: (a) DBB blocks alone (negative control group); (b) DBB blocks with superficial adsorption of 50 µg BMP-2 (ad.BMP-2 group); (c) DBB blocks coated by biomimetic CaP coating which incorporates 50 µg BMP-2 (inc.BMP-2 group); and (d) autologous bone blocks (positive control group). After 3 months of healing, samples were harvested for micro-CT and histomorphometric analyses. RESULTS: In histomorphometry, the inc.BMP-2 group showed a significantly thicker (coronal-apically) and wider (buccal-lingually) augmented bone area, better bone-to-implant contact than the negative control group. In both the micro-CT and histomorphometry, the inc.BMP-2 group showed more mineralized tissue than the negative control group and the inc.BMP-2 group also showed significantly more newly formed bone and residual grafts than the negative control group in the upper half of the blocks. In micro-CT, the inc.BMP-2 group showed significantly more bone-to-graft contact percentage than the ad.BMP-2 group. In both micro-CT and histomorphometry, the inc.BMP-2 group showed significantly more percentage of mineralized tissue than the ad.BMP-2 group. No significant differences were found between the inc.BMP-2 group and the positive control group either in micro-CT or in histomorphometry. CONCLUSIONS: The DBB blocks with coating-delivered BMP-2 significantly enhanced the efficacy of vertical alveolar bone augmentation, compared with the unloaded blocks and blocks with adsorbed BMP-2, in the one-stage onlay surgery with simultaneous implant insertion.

Periodontal regeneration using bone morphogenetic protein 2 incorporated biomimetic calcium phosphate in conjunction with barrier membrane: A pre-clinical study in dogs.

AIM: To evaluate the effect of bone morphogenetic protein 2 (BMP-2) incorporated biomimetic calcium phosphate (BMP-2/BioCaP) in conjunction with barrier membrane on periodontal regeneration in chronic periodontitis experimental model. MATERIAL AND METHODS: Chronic periodontitis experimental model with critical-sized supra-alveolar defects was created in 15 dogs' mandibles. After the initial periodontal therapy, the defects were randomly assigned to the following groups: (a) control; (b) barrier membrane; (c) deproteinized bovine bone mineral + barrier membrane; (d) BioCaP + barrier membrane and (e) BMP-2/BioCaP + barrier membrane (6 quadrants with 18 teeth per group). Eight weeks later, clinical examinations, micro-CT, and histomorphometric analyses were performed. RESULTS: Clinical examinations, including plaque index, bleeding index, and probing depth, were similar for all groups. In contrast, the clinical attachment loss was significantly lower in defects grafted with BMP-2/BioCaP and barrier membrane. The micro-CT results showed that the height of mineralized tissue in defects grafted with BMP-2/BioCaP and barrier membrane was significantly higher. For histometric analysis, the defects grafted with BMP-2/BioCaP and barrier membrane exhibited significantly more connective tissue height, new cementum height, new bone height and area, as well as less down-growth of junctional epithelium. CONCLUSION: BMP-2/BioCaP could be a promising bone substitute for periodontal regeneration.

Preclinical application of recombinant human bone morphogenetic protein 2 on bone substitutes for vertical bone augmentation: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Recombinant human bone morphogenetic protein 2 (rhBMP-2) has been introduced to clinical practice because of its osteoinductive capacity. However, the evidence of its efficacy in vertical bone augmentation procedures is not clear. PURPOSE: The purpose of this systematic review and meta-analysis was to investigate the efficacy of rhBMP-2 in vertical bone augmentation and to establish whether its addition in preclinical experiments (animal studies) would be sufficient to justify further clinical and histometric studies. MATERIAL AND METHODS: An electronic search of 3 databases, PubMed/MEDLINE, EMBASE, and Web of Science, and a manual search of the reference list of relevant studies were performed. Only randomized controlled trials regarding animal studies comparing the efficacy of bone grafts supplemented with and without rhBMP-2 in vertical bone augmentation procedures were included and reviewed. RESULTS: Nine studies were included. The results of the meta-analysis showed that the pooled weighted mean difference (WMD) of the percentage of newly formed bone was 9.97% (95% confidence interval [CI]=-0.79% to 20.72%; P=.070), the WMD of the percentage of residual materials was -21.31% (95% CI=-70.62% to 28.00%; P=.400), the WMD of the augmented bone height was 1.70 mm (95% CI=-0.23 to 3.63 mm; P=.080), the WMD of the augmented bone height for studies with space-providing barriers was 1.00 mm (95% CI=0.43 to 1.57 mm; P<.001), and the WMD of the percentage of regenerated tissue was 17.07% (95% CI=8.52% to 25.62%; P<.001). CONCLUSIONS: The application of rhBMP-2 in bone substitutes did not enhance new bone formation and residual graft resorption in vertical bone augmentation procedures. Tissue regeneration and the augmented bone height were significantly improved by the additional use of BMP-2.

Strontium ion attenuates lipopolysaccharide-stimulated proinflammatory cytokine expression and lipopolysaccharide-inhibited early osteogenic differentiation of human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease characterized by the destruction of the periodontium. The strontium ion (Sr2+ ) can prevent the bone loss associated with periodontitis and promote the regeneration of the bone. The mechanisms by which the Sr2+ works remain poorly understood. We aim to investigate the effects of the Sr2+ ion on cell proliferation, inflammatory regulation and osteogenic differentiation of human periodontal ligament cells (hPDLCs) in pathological conditions. MATERIAL AND METHODS: hPDLCs were obtained from premolars that came from the orthodontic extraction. The hPDLCs were treated with Sr2+ and/or lipopolysaccharide (LPS), which was applied as the pathological condition of periodontitis. The effect of the dose of Sr2+ on cell proliferation was analyzed using a Cell Counting Kit-8 assay. The gene and protein expression of proinflammatory cytokines were detected by the real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The osteogenic differentiation and mineralization were assessed by the real-time polymerase chain reaction, alkaline phosphatase activity assay and alizarin red staining. RESULTS: Results demonstrated that Sr2+ in a range of concentrations from 0.02 to 2.5 mmol/L significantly improved the proliferation of hPDLCs. Sr2+ reversed LPS-stimulated proinflammatory cytokine expressions such as tumor necrosis factor alpha, interleukin (IL)-1ß, IL-6 and IL-8. Moreover, Sr2+ rescued the LPS-inhibited gene expression of osteogenic differentiation. Although it appeared to suppress the late mineralization, Sr2+ can reverse the LPS-inhibited early osteogenic differentiation of hPDLCs. CONCLUSION: These results indicated that Sr2+ could attenuate the LPS-stimulated proinflammatory molecule expression and inhibit early osteogenic differentiation of hPDLCs.

Cell-mediated BMP-2 release from a novel dual-drug delivery system promotes bone formation.

OBJECTIVES: In this study, a novel biomimetic calcium phosphate bone substitute (BioCaP) is introduced as a dual-drug release system with two drug/protein delivery modes: protein is incorporated into (i) the interior of BioCaP (an internal depot); and (ii) a superficial calcium phosphate coating on BioCaP (a surface-coated depot). Our aim is to investigate each of the two delivery modes of BioCaP. Our hypotheses are that (i) both of the drug delivery modes, in in vitro as well as in vivo environment, can achieve a sustained cell-mediated protein release; and (ii) BioCaP with these two delivery modes with incorporated bone morphogenetic protein-2 (BMP-2) promotes bone formation. MATERIALS AND METHODS: Tablets of BioCaP were prepared with different carrying modes using bovine serum albumin (BSA) as model protein. The release of this protein was analysed (n = 6 per group). Granules of BioCaP with different carrying modes of BMP-2 were implanted subcutaneously in rats (n = 6 animals per group). Samples were collected after 5 weeks for histomorphometric analysis. RESULTS: In vitro data showed that the internal and surface-coated depots of BSA resulted in a sustained osteoclast-mediated release, while the adsorbed BSA was rapidly released, and this release was not affected by osteoclasts. In vivo data showed that the volume densities of bone, bone marrow, and blood vessels were significantly higher in samples where BMP-2 was incorporated internally or in the coating compared with granules with adsorbed growth factor. Osteoclast-like cells were associated with the granules, and resorption lacunae were frequently observed. CONCLUSION: It is shown that different modes of incorporation of BMP-2 on and in BioCaP granules have a beneficial effect on the formation of ectopic bone. This dual-drug release system makes BioCaP granule a promising tool for delivering multiple therapeutic agents for different clinical applications.

Icariin: does it have an osteoinductive potential for bone tissue engineering?

Traditional Chinese medicines have been recommended for bone regeneration and repair for thousands of years. Currently, the Herba Epimedii and its multi-component formulation are the attractive native herbs for the treatment of osteoporosis. Icariin, a typical flavonol glycoside, is considered to be the main active ingredient of the Herba Epimedii from which icariin has been successfully extracted. Most interestingly, it has been reported that icariin can be delivered locally by biomaterials and that it has an osteoinductive potential for bone tissue engineering. This review focuses on the performance of icariin in bone tissue engineering and on blending the information from icariin with the current knowledge relevant to molecular mechanisms and signal pathways. The osteoinductive potential of icariin could be attributed to its multiple functions in the musculoskeletal system which is involved in the regulation of multiple signaling pathways in anti-osteoporosis, osteogenesis, anti-osteoclastogenesis, chondrogenesis, angiogenesis, and anti-inflammation. The osteoinductive potential and the low price of icariin make it a very attractive candidate as a substitute of osteoinductive protein-bone morphogenetic proteins (BMPs), or as a promoter for enhancing the therapeutic effects of BMPs. However, the effectiveness of the local delivery of icariin needs to be investigated further.

In vivo validation of osteoinductivity and biocompatibility of BMP-2 enriched calcium phosphate cement alongside retrospective description of its clinical adverse events.

PURPOSE: Although bone morphogenetic protein-2 (BMP-2) possesses potent osteoinductivity, there have been some concerns on the safety of BMP-2 and BMP-2-incorporated bone substitutes used for bone formation. On the other hand, BMP-2-loaded calcium phosphate cement (BMP-2@CPC) has been developed and used for bone regeneration in oral implantology. Therefore, this study aims to investigate this product's biocompatibility and clinical safety after being used in maxillofacial surgery. MATERIALS AND METHODS: A rat model was employed to assess the osteoinduction and biocompatibility of BMP-2@CPC. Further, a retrospective investigation was carried out: 110 patients who received BMP-2@CPC treatment after their maxillofacial surgery were recruited to describe relative adverse events. RESULTS: In vivo, BMP-2@CPC showed a significantly higher mean bone volume density and osteoblasts volume density (15 ± 2% and 3 ± 1%)than those of the CPC group (p < 0.05) after being implanted in the dorsal area of rats. Regarding biocompatibility, the mean fibrous tissue volume density was significantly lower in the BMP-2@CPC group (20 ± 5% compared to 31 ± 6%, p = 0.026). The retrospective clinical study showed that only five mild/moderate adverse events were identified in four patients based on the medical records of 110 patients, including swelling, bony mass, and wound dehiscence. This adverse event occurrence was not affected by gender, age, the dose of filled materials, and operations in the study (p > 0.05). CONCLUSIONS: BMP-2-loaded CPC has osteoinductivity and more promising biocompatibility than pure CPC. However, its degradation is slower than CPC. The safety of BMP-2-loaded CPC with 0.5 or 1 mg BMP-2 is promising in oral maxillofacial surgery. CLINICAL IMPLICATIONS: This study confirmed the promising safety of this BMP-2 incorporated CPC used in dental clinical practice, which can promote its reassuring application for dental implant placement in bone insufficient areas.

Cleaning and modification of intraorally contaminated titanium discs with calcium phosphate powder abrasive treatment.

OBJECTIVE: The aim of this study was to evaluate the cleaning efficiency on intraorally contaminated titanium discs by using calcium phosphate and air powder abrasive (APA) treatment. The modification of titanium surface (SLA) was evaluated and compared with the conventional air powder abrasive methods and phosphoric acid. This treatment modality might give new perspectives for peri-implant surface treatment. MATERIALS AND METHODS: A total of 36 SLA surface titanium discs were kept in the human mouth for 48 h by 14 volunteers. The intraorally contaminated discs were stained with erythrosine dye to make the biofilm visible. Discs were randomly assigned to one of the six groups: APA without powder-only water and air (Control). APA with Hydroxylapatite (HA). APA with Hydroxylapatite and Calcium Phosphate (HA + TCP). APA with Titanium Dioxide (TiO2). APA with EMS Soft Subgingival powder (EMS). Phosphoric Acid. Light microscope photos were taken during the treatment. Following the cleaning, the residual biofilm, surface changes, and surface chemical content were evaluated using Scanning Electron Microscopy (SEM) and Energy Dispersive X-Ray Spectroscopy (EDS). A systematic random sampling protocol and a point counting method were applied for the quantitative evaluation of the remaining biofilm. Multiple comparisons within and between groups are performed by Kruskall Wallis test and if significant Mann-Whitney U-test as post hoc testing is applied. The significance level was P < 0.05. RESULTS: All methods with the exception of phosphoric acid could decrease the initial amount of biofilm significantly. Among all air powder abrasive treatments, the HA + TCP group showed the best results with 99% biofilm removal, followed by HA and EMS powders. The cleaning method caused minimal changes to the surface structure. With the exception of the control group, all air powder applications caused sharp edges around the grooves in the implant surface to be rounded. TiO2 powder caused less change than HA and HA + TCP. Phosphoric acid did not cause a visible surface change on the SEM photos. Powder particles remnants were observed on and impacted in the titanium surface. In the HA and HA + TCP group, a Ca content was observed varying between 2% and 5%. In the control group, saliva and biofilm-related elements were observed. CONCLUSIONS: Using the air powder abrasive method with calcium phosphate powders on contaminated titanium discs, an efficient implant cleaning and surface modification can be achieved. This method should be further improved as it has possible potential to be used as an implant surface treatment method for implants involved with peri-implantitis.

Long-term outcomes of short dental implants supporting single crowns in posterior region: a clinical retrospective study of 5-10 years.

OBJECTIVE: Aimed to evaluate the long-term clinical and radiographic outcomes of short implants supporting single crowns in the posterior regions. MATERIAL AND METHODS: A retrospective study design was adopted. The clinical and radiographic data of 231 short implants (intra-bony length ≤8 mm) supporting single crowns in 168 patients, were collected after 5-10 (mean 7.22) years' follow-up. Implant and prosthesis failures, peri-implant marginal bone loss, biological and technical complications were evaluated. The influence factors on implant failure were studied. RESULTS: In total 4 implants and 11 prostheses failed. The 10-year (5-year) cumulative survival rate was 98.3% (98.7%) for implant-based analysis and 97.6% (98.2%) for patient-based analysis. The short implants placed in type IV bone yielded more failures than in type I-III and presented a survival rate of 94.0%. The 10-year survival rate of the prostheses was 95.2%. The mean marginal bone loss between implant installation and the 10 years' follow-up visit was 0.63 ± 0.68 mm. The marginal bone loss between the first and 5th year was minimal (0.05 ± 0.10mm and not statistically significant). 18 (7.8%) implants were exposed to biological complications, whereas 29 (12.6%) implants were involved in technical complications. CONCLUSIONS: High survival rates for both the implants and the prostheses could be achieved after 5-10 years for short implants supporting single crowns, without severe marginal bone loss and complications. One may conclude that a single crown supported by a short implant is a predictable treatment modality. However, short implants in type IV bone sites should be applied with caution.

Gaining Soft Tissue with a Hydrogel Soft Tissue Expander: A Case Report.

In this case report, we describe the treatment of a patient referred to our clinic with a hopeless tooth 21 with an attached pontic. The aim of this case report was to, first, describe the advantages and disadvantages of gaining soft tissue with a self-inflating soft tissue expander before performing a bone augmentation procedure in implant dentistry in the esthetic zone. Second, we describe how an amalgam tattoo, caused by a previously performed apicoectomy that made the extension of the raised flap to cover the augmented site esthetically undesirable, was removed. Two silicone enveloped Osmed hydrogel self-inflating soft tissue expanders were placed submucosally on the right- and left-hand side of the amalgam tattoo. One of these two perforated the overlaying mucosa after 24 days. Both tissue expanders were removed, the amalgam tattoo was excided, the site augmented, and an implant with a crown and a pontic was placed.

Icariin Has a Synergistic Effect on the Osteoinductivity of Bone Morphogenetic Protein 2 at Ectopic Sites.

OBJECTIVE: Establishing biocompatible, biodegradable, osteoconductive, and osteoinductive bone materials remains a challenging subject in the research of bone healing and bone regeneration. Previously, we demonstrated the osteogenic and osteoconductive effects of biomimetic calcium phosphate (BioCaP) incorporating with Icariin and/or bone morphogenetic protein 2 (BMP-2) at orthotopic sites. METHODS: By implanting the BioCaP granules incorporated Icariin and/or BMP-2 into the dorsal subcutaneous pockets of adult male Sprague-Dawley (S-D) rats (6-7 weeks old), we investigated the osteoinductive efficacy of the samples. Micro-computed tomography(micro-CT) observations and histological slices were used to verify the osteoinduction of this system on the 2nd and 5th week. Statistical significances was evaluated using Turkey's post hoc test of one-way analysis of variance. RESULTS: The osteoinduction of the BioCaP incorporated with BMP-2 or both agents was confirmed as expected. BioCaP with Icariin alone could not generate bone formation at an ectopic sites. Nevertheless, co-administration of Icariin increased bone mineral density (BMD; p < 0.01) (628mg HA/cm3 vs 570mg HA/cm3 ) and completely changed the distribution of newly formed bone when compared with the granules with BMP-2 alone, even though there was no significant difference in the volume of newly formed bone. In contrast, the BioCaP with both agents (37.86%) had significantly fewer remaining materials than the other groups by the end of the fifth week (53.22%, 53.62% and 48.22%) (p < 0.01). CONCLUSION: The co-administration of Icariin and BMP-2 increased BMD changed the distribution of newly formed bone, and reduced the amount of remaining materials. Therefore, Icariin can stimulate BMP-2 when incorporated into BioCaP granules at ectopic sites, which makes it useful for bone tissue engineering.

Biomimetic calcium phosphate coating on medical grade stainless steel improves surface properties and serves as a drug carrier for orthodontic applications.

OBJECTIVE: Recently, stainless steel (SSL) miniscrew implants have been used in orthodontic clinics as temporary anchorage devices. Although they have excellent physical properties, their biocompatibility is relatively poor. Previously, our group developed a two-phase biomimetic calcium phosphate (BioCaP) coating that can significantly improve the biocompatibility of medical devices. This study aimed to improve the biocompatibility of SSL by coating SSL surface with the BioCaP coating. METHODS: Titanium (Ti) discs and SSL discs (diameter: 5 mm, thickness: 1 mm) were used in this study. To form an amorphous layer, the Ti discs were immersed in a biomimetic modified Tyrode solution (BMT) for 24 h. The SSL discs were immersed in the same solution for 0 h, 12 h, 24 h, 36 h and 48 h. To form a crystalline layer, the discs were then immersed in a supersaturated calcium phosphate solution (CPS) for 48 h. The surface properties of the BioCaP coatings were analysed. In addition, bovine serum albumin (BSA) was incorporated into the crystalline layer during biomimetic mineralisation as a model protein. RESULTS: The morphology, chemical composition and drug loading capacity of the BioCaP coating on smooth SSL were confirmed. This coating improved roughness and wettability of SSL surface. In vitro, with the extension of BMT coating period, the cell seeding efficiency, cell spreading area and cell proliferation on the BioCaP coating were increased. SIGNIFICANCE: These in vitro results show that the BioCaP coating can improve surface properties of smooth medical grade SSL and serve as a carrier system for bioactive agents.

Radiographic and histological evaluation of bone formation induced by rhBMP-2-incorporated biomimetic calcium phosphate material in clinical alveolar sockets preservation.

PURPOSE: We assessed the efficiency of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) incorporated biomimetic calcium phosphate on ß-tricalcium phosphate (ß-TCP) (rhBMP-2/BioCaP/ß-TCP) on bone formation in a model of socket preservation using cone beam computed tomography (CBCT) scanning and histological examination. METHODS: Forty patients undergoing minimally invasive single-root tooth extraction for dental implantation were randomized to three groups according to the material used for socket preservation: filling with rhBMP-2/BioCaP/ß-TCP, ß-TCP, or natural healing (kept unfilled) (controls). The alveolar sockets (including the control group) were covered by two-layer collagen membranes and sutured. Two CBCT scans were taken, one immediately after socket preservation procedure (baseline) and another 6 weeks later. Gray values (GVs) obtained from CBCT were recorded. During insertion of the dental implant, biopsies were taken and analyzed histologically for new bone formation, residual material, and unmineralized bone tissue at the core of the biopsy. RESULTS: The mean (± standard deviation) changes of GVs of the CBCT scans at the central area of filled materials were as follows: 373.19 ± 157.16 in the rhBMP-2/BioCaP/ß-TCP group, 112.26 ± 197.25 in the ß-TCP group, and -257 ± 273.51 in the control group. The decrease of GVs in the rhBMP-2/BioCaP/ß-TCP group as compared with the ß-TCP group was statistically significant (P < 0.001). Differences in new bone formation (P = 0.006) were also found: 21,18% ± 7.62% in the rhBMP-2/BioCaP/ß-TCP group, 13.44% ± 6.03% in the ß-TCP group, and 9.49% ± 0.08% in controls. The residual material was10.04% ± 4.57% in the rhBMP-2/BioCaP/ß-TCP group vs. 20.60% ± 9.54%) in the ß-TCP group (P < 0.001). Differences in unmineralized bone tissue (P < 0.001) were also found (68.78% ± 7.67%, 65.96% ± 12.64%, and 90.38% ± 7.5% in the rhBMP-2/BioCaP/ß-TC, ß-TCP, and control groups, respectively). CONCLUSIONS: This study shows that rhBMP-2/BioCaP/ß-TCP is a promising bone substitute with fast degradation and potent pro-osteogenic capacity that can be useful for socket preservation in implant dentistry. TRIAL REGISTRATION: ChiCTR, ChiCTR2000035263. Registered 5 August 2020, https://www.chictr.org.cn/ChiCTR2000035263 .

Calcium Phosphate Ceramics and Synergistic Bioactive Agents for Osteogenesis in Implant Dentistry.

Implant-supported dental prosthetics are widely used in dental practice. Sufficient peri-implant bone tissue is a crucial prerequisite for the long-term success of this treatment, as insufficient peri-implant bone volume hampers dental implant installation and negatively influences dental implant stability. However, due to tooth extraction, bone metabolism diseases, and trauma, bone defects in the jaw are common in patients, particularly in the elderly and those suffering from underlying conditions. If this is the case, the alveolar ridge has to be augmented for reliable implant placement. Various biomaterials, growth factors (GFs) or GF-based products, and trace elements have been tested and used for alveolar ridge augmentation. Among those biomaterials, calcium phosphates (CaPs) are the most popular due to their promising biocompatibility, great osteoconductivity, and distinguishing osteogenesis. Combining CaPs with GFs or trace elements can further favor bone defect repair. This review mainly focuses on applying artificial CaP biomaterials and their combination with bioactive agents to repair bone defects in implant dentistry.

Virtual pterygoid implant planning in maxillary atrophic patients: prosthetic-driven planning and evaluation.

PURPOSE: The study aims to use cone beam computed tomography (CBCT) to (1) define the virtual valid length of pterygoid implants in maxillary atrophic patients from the prosthetic prioritized driven position and (2) measure the implant length engaged in the pterygoid process according to the HU difference of the pterygoid maxillary junction. MATERIALS AND METHODS: Virtual pterygoid implants were planned with CBCT of maxillary atrophic patients in the software. The entry and angulation of the implant were planned according to the prosthetic prioritized driven position in the 3D reconstruction image. The planned implant length and the valid length defined as the implant between the pterygoid maxillary junction and pterygoid fossa were recorded. The relationship between the implant and sinus cavity was also evaluated. RESULTS: A total of 120 CBCT samples were enrolled and virtually planned. The mean age of the patients was 56.2 ± 13.2 years. One hundred and sixteen samples could successfully place virtual implants according to the criterion. The mean implant length and mean implant length beyond the pterygoid maxillary junction were 16.3 ± 4.2 mm (range, 11.5-18 mm) and 7.1 ± 3.3 mm (range, 1.5-11.4 mm), respectively. Ninety percent of virtually planned implants had a close relationship with the sinus cavity, and implants exhibited longer lengths when they had no relation with the sinus. CONCLUSION: From a prosthetic prioritized driven position with fixed entry and angulation, pterygoid implants achieve adequate bone anchorage length beyond the pterygoid maxillary junction. Due to the individual anatomy and the volume of the maxillary sinus, the implants presented a different positional relationship with the maxillary sinus.