OBJECTIVE:To screen decontamination efficacy of three combinatory protocols and to evaluate the regenerative efficacy of bone morphogenetic protein 2-incorporated biomimetic calcium phosphate granules (BMP2-inc. BioCaP) in treating implants with peri-implantitis. MATERIAL AND METHODS:Peri-implantitis model was established on 24 dental implants in 6 beagle dogs. The implants were decontaminated using mechanical curettage (MC) with either Chlorhexidine (CHX), photodynamic therapy (PDT), or both. The decontamination efficacy was assessed by measuring modified Sulcus Bleeding Index (mSBI), probing pocket depth (PPD), peri-implant sulcular fluid (PISF), and inflammatory cytokines of crevicular fluid (IL-8, IL-1β). Thereafter, GBR surgery was performed either without (Control) or with deproteinized bovine bone mineral (DBBM) or with BMP2-inc. BioCaP. Three fluoresceins were consequentially injected to assess bone growth rates. Eight weeks post-surgery, samples were subjected to micro-CT, confocal laser scanning microscopy and histomorphometric analyses. RESULTS:MC + CHX + PDT was associated with the lowest levels of mSBI, PPD, PISF, IL-1β, and IL-8 2 weeks post decontamination. Eight weeks post GBR surgery, BMP2-inc. BioCaP yielded significantly higher bone volume fraction, trabecular thickness, trabecular number, bone mineral density, and significantly lower trabecular separation than DBBM and Control. BMP2-inc. BioCaP bore significantly higher total fluorescence intensities than DBBM and Control at 2, 4, and 6 weeks, and was also associated with significantly higher bone-to-implant contact and new bone height than DBBM and Control. CONCLUSIONS:Within the limitations of this study, MC + CHX + PDT decontamination and BMP-2-incorporated BioCaP showed an application potential in treating peri-implantitis. Further studies with a long monitoring span are necessary before clinical application.

Early immune homeostasis at the biomaterial-tissue interface is a critical engineering challenge for osseointegration success. While strontium (Sr)-modified biomaterials exhibit advantages in enhancing osseointegration, the immunomodulatory effects of localized Sr release, particularly on upstream monocytes, remain unelucidated. This study aims to delineate Sr-reprogrammed monocyte subset dynamics and the underlying mechanism. Here, we engineered Sr-doped sandblasted, large-grit, and acid-etched (Sr-SLA) titanium implants. Sr-SLA implants ameliorated the early inflammatory microenvironment and promoted osseointegration. To decipher the Sr-modulated immune microenvironment, we employed single-cell RNA sequencing, which revealed that monocytes constituted the largest proportion of cells surrounding implants, with subset distribution correlating with osteogenic efficiency. Notably, Sr-SLA implants suppressed the activation of pro-inflammatory classical monocytes (Ly6Chi), with high transient receptor potential melastatin 2 (TRPM2) and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) expression, while promoting the expansion of regenerative nonclassical monocytes (Ly6Clo), exhibiting low TRPM2 and NLRP3 levels. Further validation demonstrated that Sr ions inhibited NLRP3 inflammasome activation in monocytes via blocking TRPM2 expression and calcium influx, leading to reduced pro-inflammatory cytokine (interleukin-1β and interleukin-18) secretion. Meanwhile, a conditioned medium from Sr-SLA-cultured monocytes exerted robust osteogenic potential by markedly facilitating bone marrow mesenchymal stromal cells' osteogenic differentiation, due to a Sr-reshaped cytokine profile. Moreover, in vivo study corroborated that monocyte depletion impaired osseointegration, underscoring its indispensable role in implant-mediated bone regeneration. Collectively, Sr-SLA implants reprogrammed monocyte subsets via the TRPM2-Ca2+-NLRP3 axis, reshaping the early inflammatory microenvironment to enhance osseointegration. This study establishes a cascade linking material properties, early immune response, and bone regeneration, providing an engineerable target for designing immunomodulatory biomaterials.

The immune system and biomaterials exhibit a well-documented synergistic interplay, essential for bone defect healing. Calcium phosphate (CaP) biomaterials, notably hydroxyapatite, β-tricalcium phosphate, and biphasic calcium phosphate, are widely employed as bone substitutes due to their inherent osteoconductivity. A key challenge for synthetic CaPs is augmenting their osteoinductive potential. Indeed, the limited translation of biomaterials into clinical practice may largely stem from insufficient immunomodulatory understanding. Current evidence reveals the complex host immune response to CaPs, which is mediated by physical and biochemical properties. Harnessing immunomodulatory strategies could bridge inflammatory modulation and osteogenesis, thereby enhancing bone regeneration. This review systematically analyzes recent advances in the molecular mechanisms of immune cell responses to CaPs during bone defect healing, deepening our understanding of immunomodulatory strategies for bone regeneration. Furthermore, key knowledge gaps are highlighted to inspire the development of spatiotemporally responsive CaPs for bone tissue engineering.

The regeneration of critical-sized bone defects is severely hampered by a dual challenge: insufficient vascularization and limited osteogenic activity at the injury site. Histatin-1 (Hst1), a salivary peptide with known pro-angiogenic and regenerative activities, is a hopeful candidate for bone regeneration, yet its dual function in osteogenesis and angiogenesis remains underexplored. Here, we systematically elucidated this dual function. In vitro, Hst1 was demonstrated to stimulate the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) through the activation of the Wnt/β-catenin signaling pathway. Concurrently, Hst1 promoted tube formation through paracrine signaling. In vivo, the hydrogel formulated from oxidized sodium alginate (OSA), gelatin (GE), and adipic acid dihydrazide (ADH) was employed to ensure the sustained delivery of Hst1. This Hst1-loaded hydrogel was applied to a 5-mm critical-sized cranial defect in rats. Compared to the Control group, Hst1-loaded hydrogel significantly enhanced bone regeneration, with the bone volume fraction (BV/TV) increasing to 20.0 % (vs. 8.2 % for Control). This was accompanied by a marked increase in vascularization, as evidenced by a 3.0-fold rise in vessel density. In conclusion, this study reveals the dual pro-regenerative function of Hst1 in simultaneously promoting osteogenesis and angiogenesis, demonstrating that harnessing Hst1 within a sustained-release hydrogel is a powerful therapeutic strategy for achieving vascularized bone regeneration.

Aim or purpose: To assess the clinical and radiographic outcomes of TSFE with or without bone grafting in atrophic maxilla. Materials and methods: This retrospective study included 234 patients with RBH of 3-5mm who underwent TSFE, divided into Group 1 (with bone grafting, n=141) and Group 2 (without bone grafting, n=93). Patient medical histories were collected, and radiographic parameters were measured at four timepoints: preoperative (T0), immediate postoperative (T1), healing phase (T2, 4-6 months postoperatively), and follow-up period (T3, 1-6 years postoperatively). The primary outcomes were implant survival rate and endo-sinus bone gain volume (ESBGV). Secondary outcomes included: complication incidence rate, peri-implant soft tissue parameters, and marginal bone loss (MBL). A multiple linear regression model was employed to identify key determinants influencing endo-sinus bone augmentation following TSFE. Results: The survival rate was 98.05% for Group 1 and 98.99% for Group 2, with no significant difference in the two groups. Group 2 achieved more ESBGV than Group 1 at T2/T3 phase, with Group 2 showing progressive resorption over 3 years versus early stabilization in Group 1. No significant differences in complication incidence rate, MBL and peri-implant tissue parameters were found. Immediate postoperative sinus lift volume showed a significant positive correlation with ESBGV. Conclusions: TSFE is a reliable treatment option in atrophic maxilla, while bone grafting material enhanced sinus bone augmentation but did not improve survival rate. Except of bone grafting material, immediate postoperative sinus lift volume was the primary predictor of bone augmentation.

Autophagy is a critical factor in eukaryotic evolution. Cells provide nutrition and energy during autophagy by destroying non-essential components, thereby allowing intracellular material conversion and managing temporary survival stress. Autophagy is linked to a variety of oral disorders, including the type and extent of oral malignancies. Furthermore, autophagy is important in lymphocyte formation, innate immunity, and the regulation of acquired immune responses. It is also required for immunological responses in the oral cavity. Knowledge of autophagy has aided in the identification and treatment of common oral disorders, most notably cancers. The involvement of autophagy in the oral immune system may offer a new understanding of the immune mechanism and provide a novel approach to eliminating harmful bacteria in the body. This review focuses on autophagy creation, innate and acquired immunological responses to autophagy, and the status of autophagy in microbial infection research. Recent developments in the regulatory mechanisms of autophagy and therapeutic applications in oral illnesses, particularly oral cancers, are also discussed. Finally, the relationship between various natural substances that may be used as medications and autophagy is investigated.

PURPOSE:To evaluate the short-term effect of dental implant placement, mucosa thickness, and their combined effects (initial biologic width) on marginal bone loss.MATERIALS AND METHODS:This was a retrospective study on patients who received implant surgery in the posterior region without bone augmentation surgery between 2012 and 2016, and implants had been loaded for more than 12 months. Each patient received radiographic examination before and after implant surgery, before the stage-two surgery, and during the 1- to 5-year follow-up. The thickness of mucosa, depth of dental implant placement, and crestal bone loss were evaluated on digital radiographs. The interaction was discussed by defining the combination of initial mucosal thickness and implantation depth as the initial biologic width. The implants were divided into four study groups based on the quartile of the initial biologic width.RESULTS:This study included 266 patients (94 male and 172 female, 22 to 85 years of age, mean age: 51.43 years), with 413 dental implants placed including 239 Straumann implants and 174 Ankylos implants. The average follow-up was 21.50 months. After 1 to 5 years, the median crestal bone loss around implants was 0.35 mm (0.30 mm for Straumann BL and 0.40 mm for Ankylos). The implants were divided into four groups: group A (≤ 2.85 mm), group B (2.85 to 3.40 mm), group C (3.40 to 3.97 mm), and group D (> 3.97 mm). Group B showed significantly less crestal bone loss than group A (0.38 mm vs 0.25 mm; P < .05) and group C (0.25 mm vs 0.40 mm; P < .05) during the follow-up. Significantly more crestal bone loss around implants was observed in the thin mucosa group than in the thick mucosa group (0.50 mm vs 0.30 mm; P < .001), while implants placed beneath the bone level displayed a significantly higher amount of marginal bone loss than implants placed even with the bone crest (0.50 mm vs 0.10 mm; P < .001).CONCLUSION:The initial biologic width has an effect on crestal bone loss. When the initial biologic width was between 2.85 and 3.40 mm, the marginal bone loss was lowest. Based on radiographic evaluation, implants placed in thick gingiva and even with the bone level showed less alveolar marginal bone loss compared with implants placed in thin gingiva and below the crestal bone level.

Antibiotics are often used to treat systemic diseases not associated with the oral cavity. This application of antibiotics may affect the healthy oral microbiota community, as it destroys the balance between specific bacterial populations throughout the ecosystem and may lead to dysbacteriosis. We hypothesized that the effects on antibiotics on oral microbiota regulation and function would affect antibody content in saliva, depending on the antibiotic type. To address this, a total of 24 Sprague Dawley rats (divided into 4 cages, 6 per pen) were administered amoxicillin (AMX), spiramycin (SP), metronidazole (MTZ), or water (control) daily for 14 days (gavage). After treatment was completed, high-throughput sequencing of 16S rRNA genes was used to determine changes in the composition, metabolic function, and diversity of oral microbiota in the rats. Enzyme-linked immunosorbent assay was used to detect antibodies in saliva, including SIgA, IgG, and IgM. Results showed that AMX, MTZ, and SP significantly affected oral microbiota composition, diversity, and metabolic function in rats. AMX induced substantial changes in the rat salivary antibody concentrations. At the genus level, the relative abundance of Rothia and Haemophilus was higher in the AMX group than in the other groups. In conclusion, antibiotics-induced changes in oral microbiota populations may be associated with changes in salivary antibody concentrations. However, the specific interaction mechanisms remain unknown, and it is still unclear whether significant changes in the oral microbiota cause changes in salivary antibody concentrations or vice versa.

A biphasic calcium-phosphate (CaP)-coating is a promising surface modification for functionalizing various endosseous biomaterials. However, its biomedical application is limited by its low coating yield and incorporation inefficiency. We developed a highly concentrated (4.5×) supersaturated calcium-phosphate solution (SCPS) and compared its physicochemical properties with those of 1× SCPS. One milliliter of 4.5× SCPS formed a thick (110 μm) continuous coating on a titanium disc (4×4×1 mm), compared to the thin (29 μm) 1× SCPScoating. On X-ray diffraction analysis, the 4.5× SCPS-coating had characteristic dicalcium-phosphate dehydrate and apatite peaks, in contrast to the apatite-only of 1× SCPS-coating. Under acidic condition (pH 4.5), the 4. × 5SCPS-coating released significantly less Ca2+ than the 1× SCPS-coating. FITC-bovine serum albumin incorporation in the 4.5× SCPS-coating (81.20±6.42%) was significantly higher than in the 1× SCPS-coating (21.86±1.90%). Thus, this modified coating procedure holds promise for biomedical applications.

关节软骨缺损的修复是临床尚未解决的重要问题.光聚合水凝胶具备优良的生物相容性、生物降解性以及通过光照对水凝胶时间空间的精准功能调控能力,可作为软骨组织工程优良的应用材料,具备极大的应用潜力.本文就光聚合水凝胶的材料类别、性能、在软骨组织工程中的应用进行综述,为光聚合水凝胶的临床应用提供参考.

Lung cancer represents one of the malignancies in which the 3 elements of conventional therapy (ie, surgery, radiotherapy, and chemotherapy) have limited effectiveness in curbing progressive disease. In this context, there is burgeoning interest in the use of vaccine therapy as a nontoxic adjunct to increase the treatment success rates over those obtained with traditional regimens alone. Several clinical trials using a variety of vaccination strategies have been reported or are ongoing. In this review, we have provided an overview of these trials, with a special focus on the clinical efficacy of the vaccines. The future prospects and challenges of vaccine therapy in lung cancer have also been discussed.

The avascular structure and lack of regenerative cells make the repair of osteochondral defects in the temporomandibular joint (TMJ) highly challenging in the clinic. To provide a viable treatment option, we developed a methacrylated gelatin (Gel-MA) hydrogel functionalized with human salivary histatin-1 (Hst1). Gel-MA is highly biocompatible, biodegradable, and cost-effective. Hst1 is capable of activating a series of cell activities, such as adhesion, migration, differentiation, and angiogenesis. To evaluate the efficacy of Hst1/Gel-MA, critical-size osteochondral defects (3 mm in diameter and 3 mm in depth) of TMJ in New Zealand white rabbits were surgically created and randomly assigned to one of the three treatment groups: (1) control (no filling material); (2) Gel-MA hydrogel; (3) Hst1/Gel-MA hydrogel. Samples were retrieved 1, 2, and 4 weeks post-surgery and subjected to gross examination and a series of histomorphometric and immunological analyses. In comparison with the control and Gel-MA alone groups, Hst1/Gel-MA hydrogel was associated with significantly higher International Cartilage Repair Society score, modified O'Driscoll score, area percentages of newly formed bone, cartilage, collagen fiber, and glycosaminoglycan, and expression of collagen II and aggrecan. In conclusion, Hst1/Gel-MA hydrogels significantly enhance bone and cartilage regeneration, thus bearing promising application potential for repairing osteochondral defects.

Purpose: To investigate the protective effect of bisleuconothine A on periodontal tissue in rats and the mechanism involved. Methods: Adult male Sprague Dawley rats (n = 32) weighing 180 - 200 g (mean weight, 190 ± 10 g) were randomly assigned to four groups of eight rats each: control group, periodontitis group, bisleuconothine A (50 mg/kg) group and bisleuconothine A (100 mg/kg) group. Rats in the treatment groups received bisleuconothine intraperitoneally for two weeks. Periodontitis was induced in the rats using standard procedures. Serum and tissue samples were used for biochemical analysis. Alveolar bone loss was measured in rat maxillae, while the activity of bone alkaline phosphatase (BALP) was determined in serum. Tumor necrosis factor α (TNF-α) interleukin-1β and interleukin-6 (IL-1β and IL-6) were determined in gingival tissue using enzyme-linked immunosorbent assay (ELISA) kit. Gene and protein expressions of receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and matrix metallopeptidase-9 (MMP-9) were measured in gingival tissue using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Results: Bisleuconothine A treatment significantly and dose-dependently reduced alveolar bone loss, as well as serum levels of TNF-α, IL-1β and IL-6, but increased BALP activity in periodontitis rats (p < 0.05). It also significantly and dose-dependently reduced mRNA expressions of RANKL and MMP-9, but significantly increased OPG mRNA expression (p < 0.05). Similarly, treatment with bisleuconothine A significantly and dose-dependently down-regulated RANKL, p-NF-kB, p-IkBα and iNOS proteins in gingival tissue of periodontitis rats (p < 0.05). The results of histopathological examination indicated that bisleuconothine A treatment significantly reversed histological changes in periodontal tissues of periodontitis rats. It also significantly reduced the degree of polymorphonuclear (PMN) cell infiltration in periodontal tissue. Conclusion: The results obtained show that bisleuconothine A protects periodontal tissue via the regulation of RANKL expression and infiltration of inflammatory cells. Keywords: Bisleuconothine A, Expression, Inflammation, Periodontitis, RANKL

AIM:This study measured the two-dimensional size of soft and hard tissues and analysed some relevance between them.MATERIAL AND METHODS:Ninety-six maxillary anterior implants with a follow-up time 1-7 years postoperatively were evaluated. We superimposed the CBCT data of 72 patients with the optical scan data, followed by the measurements of the thickness and the height of soft and bone tissues. The shoulder of the implant was the reference point for all vertical measurements.RESULTS:At the level of implant shoulder, the mid-buccal mean thickness of soft tissue was 1.83 ± 0.76 mm, and on the palatal side, it was 4.00 ± 1.22 mm. The mean height of mid-buccal and mid-palatal gingiva was 4.16 ± 1.07 mm and 4.27 ± 1.07 mm. The buccal and palatal vertical bone wall peak was 0.41 ± 0.73 mm and 0.22 ± 0.57 mm coronal to the implant shoulder, and the marginal bone loss was -0.28 ± 0.76 mm and -0.84 ± 1.41 mm. Correlation analysis showed that the soft tissue thickness was negatively correlated with the bone thickness at 0 mm on the buccal side and at 0/2/4 mm on the palatal side apical towards from implant shoulder. The gingival height was significantly positively correlated with bone peak height and marginal bone height.CONCLUSION:Soft and hard tissues were basically negatively correlated in the horizontal direction. Sites with little marginal bone loss or high bone peak positively correlated with higher soft tissue levels.

Large‐volume bone defects can result from congenital malformation, trauma, infection, inflammation and cancer. At present, it remains challenging to treat these bone defects with clinically available interventions. Allografts, xenografts and most synthetic materials have no intrinsic osteoinductivity, and so an alternative approach is to functionalize the biomaterial with osteoinductive agents, such as bone morphogenetic protein 2 (BMP2). Because it has been previously demonstrated that human salivary histatin‐1 (Hst1) promotes endothelial cell adhesion, migration and angiogenesis, we examine here whether Hst1 can promote BMP2‐induced bone regeneration. Rats were given subcutaneous implants of absorbable collagen sponge membranes seeded with 0, 50, 200 or 500 μg Hst1 per sample and 0 or 2 μg BMP2 per sample. At 18 days postsurgery, rats were sacrificed, and implanted regional tissue was removed for micro computed tomography (microCT) analyses of new bone (bone volume, trabecular number and trabecular separation). Four samples per group were decalcified and subjected to immunohistochemical staining to analyze osteogenic and angiogenic markers. We observed that Hst1 increased BMP2‐induced new bone formation in a dose‐dependent manner. Co‐administration of 500 μg Hst1 and BMP2 resulted in the highest observed bone volume and trabecular number, the lowest trabecular separation and the highest expression of osteogenic markers and angiogenic markers. Our results suggest that coadministration of Hst1 may enhance BMP2‐induced osteogenesis and angiogenesis, and thus may have potential for development into a treatment for large‐volume bone defects.

Promoting cell spreading is crucial to enhance bone healing and implant osteointegration. In this study, we investigated the stimulatory effect of human salivary histatin-1 (Hst-1) on the spreading of osteogenic cells in vitro as well as the potential signaling pathways involved. Osteogenic cells were seeded on bio-inert glass slides with or without the presence of Hst1 in dose-dependent or time-course assays. 1 scrambled and 6 truncated Hst1 variants were also evaluated. Cell spreading was analyzed using a well-established point-counting method. Fluorescent microscopy was adopted to examine the cellular uptake of fluorescently labeled Hst1 (F-Hst1) and also the cell spreading on sandblasted and acid etched titanium surfaces. Signaling inhibitors, such as U0126, SB203580, and pertussis toxin (PTx) were used to identify the potential role of extracellular-signal-regulated kinase, p38 and G protein-coupled receptor pathways, respectively. After 60 min incubation, Hst1 significantly promoted the spreading of osteogenic cells with an optimal concentration of 10 μM, while truncated and scrambled Hst1 did not. F-Hst1 was taken up and localized in the vicinity of the nuclei. U0126 and SB2030580, but not PTx, inhibited the effect of Hst1. 10 μM Hst1 significantly promoted the spreading of osteogenic cells on both bio-inert substrates and titanium SLA surfaces, which involved ERK and p38 signaling. Human salivary histatin-1 might be a promising peptide to enhance bone healing and implant osteointegration in clinic.

目的 探讨仙灵骨葆胶囊对去势大鼠股骨形态计量学和成骨相关基因骨钙素(OCN)、核心结合因子(Cbfα1)mRNA的影响.方法 50只6月龄雌性SD大鼠,随机分为A组(作为空白对照)、B组(作为模型)、C组(给予高剂量仙灵骨葆胶囊)、D组(给予低剂量仙灵骨葆胶囊)、E组[给予阿仑膦酸钠维D3片(福美加)],每组10只.药物干预3个月后,采用X线显微断层显像仪检测左侧离体股骨骨密度(BMD)和骨小梁数量(TbN),逆转录-聚合酶链式反应(RT-PCR)检测右侧股骨组织OCN、Cbfα1 mRNA表达,比较各组检测结果.结果 干预3个月后,B组左侧股骨BMD、TbN明显低于A组,差异具有统计学意义(P<0.05);与B组比较,C、E组左侧股骨BMD明显增高,E组左侧股骨TbN明显增高,差异具有统计学意义(P<0.05);与E组比较,C、D组左侧股骨BMD、TbN明显降低,差异具有统计学意义(P<0.05);五组左侧股骨BMD、TbN比较差异具有统计学意义(F=86.400、28.027,P<0.05).干预3个月后,与A组比较,B组右侧股骨Cbfα1、OCN mRNA表达量明显降低,差异具有统计学意义(P<0.05);与B组比较,C、D、E组右侧股骨Cbfα1 mRNA表达量明显增高(P<0.05),C、E组右侧股骨OCN mRNA表达量明显增高,差异具有统计学意义(P<0.05);与E组比较,C组右侧股骨Cbfα1和OCN mRNA表达量明显增高(P<0.05),D组右侧股骨Cbfα1 mRNA表达量明显降低,差异具有统计学意义(P<0.05);五组大鼠右侧股骨Cbfα1、OCN mRNA比较差异具有统计学意义(F=13.233、48.338,P<0.05).结论 仙灵骨葆胶囊提高去势大鼠股骨BMD可能是通过提高OCN、Cbfα1 mRNA表达量发挥作用,TbN和BMD及成骨基因OCN、Cbfα1之间的关系尚需要进一步研究.

Objectives This study identified potential general influencing factors for a mathematical prediction of implant stability quotient (ISQ) values in clinical practice. Methods We collected the ISQ values of 557 implants from 2 different brands (SICace and Osstem) placed by 2 surgeons in 336 patients. Surgeon 1 placed 329 SICace implants, and surgeon 2 placed 113 SICace implants and 115 Osstem implants. ISQ measurements were taken at T1 (immediately after implant placement) and T2 (before dental restoration). A multivariate linear regression model was used to analyze the influence of the following 11 candidate factors for stability prediction: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting, insertion torque, I-stage or II-stage healing pattern, implant diameter, implant length and T1-T2 time interval. Results The need for bone grafting as a predictor significantly influenced ISQ values in all three groups at T1 (weight coefficients ranging from -4 to -5). In contrast, implant diameter consistently influenced the ISQ values in all three groups at T2 (weight coefficients ranging from 3.4 to 4.2). Other factors, such as sex, age, I/II-stage implantation and bone type, did not significantly influence ISQ values at T2, and implant length did not significantly influence ISQ values at T1 or T2. Conclusions These findings provide a rational basis for mathematical models to quantitatively predict the ISQ values of implants in clinical practice.

This study aimed to compare the effects of bone morphogenetic protein BMP2/7 heterodimer and BMP homodimers on bone regeneration in bone defects model. Identical peri-implant bone defects model were created using proper controls on the frontal skull in 18 minipigs. Collagen sponges with low-dose (30 ng/mL) BMP2/7 heterodimer, BMP2 or BMP7 homodimer were filled in the defects. New bone formation and the expression of type I collagen (Col1), alkaline phosphatase (ALP) and osteocalcin (OCN) were evaluated after 2, 3, and 6 weeks of implantation. BMP2/7 resulted in significantly higher new bone areas percentage in the defect region than BMP2 and BMP7 (p<0.05). Immunohistochemical staining of Col1, ALP and OCN was stronger in BMP2/7 group than BMP2, BMP7 and control group (p<0.05). These results demonstrate that BMP2/7 heterodimer is a stronger inducer of osteoblastogenesis and could be applied at low dose to reduce the cost and side effects of BMP homodimers.

Heterodimeric bone morphogenetic proteins (BMPs) were exhibited to be more potent than and thus potential substitutes for homodimeric BMPs whose clinical application is limited for the drawbacks resulted from their higher effective doses. This study aims to delineate the biofunctional characteristics of recombinant human BMP2/7 (rhBMP2/7) heterodimer in inducing osteoblastogenesis of MC3T3-E1 through in vitro time-course and dose-response studies. rhBMP2/7 heterodimer induced cell migration with a significantly lower optimal concentration and higher peak effect than the respective homodimers. rhBMP2/7 heterodimer induced cell differentiation with significantly lower threshold concentrations but similar maximum effects. On day 28, the area of calcium depositions induced by 50 ng/mL rhBMP2/7 was 12- or 38-fold more than that of 50 ng/mL rhBMP2 or 50 ng/mL rhBMP7, respectively. The results indicated that rhBMP2/7 heterodimer was an osteoblastogenesis inducer of not higher potency but lower effective concentration compared with rhBMP2 and rhBMP7 homodimers.