Treatment outcomes of digital nasoalveolar moulding in infants with cleft lip and palate: A systematic review with meta-analysis.

The aim of this systematic review was to compare the treatment outcomes of digital nasoalveolar moulding (dNAM) technique with conventional nasoalveolar moulding (cNAM) or non-presurgical intervention protocol in infants with unilateral (UCLP) or bilateral (BCLP) cleft lip and palate. A bibliometric search by MEDLINE (via Ovid), Embase, Cochrane Library, grey literature and manual method was conducted without language restriction until November 2023. Literature screening and data extraction were undertaken in Covidence. The risk of bias was evaluated using the Newcastle-Ottawa Scale and RoB-2. Pooled effect sizes were determined through random-effects statistical model using R-Software, and the certainty of evidence was assessed using the GRADE approach. Among 775 retrieved articles, nine studies were included for qualitative synthesis (6-UCLP, 3-BCLP), with only three eligible UCLP studies for meta-analysis. In the UCLP group, very low certainty of evidence indicated no difference in alveolar cleft width (SMD, 0.13 mm; 95% CI, -0.31 to 0.57; I2, 0%), soft tissue (lip) cleft gap, nasal width, nasal height, and columellar deviation angle changes between dNAM and cNAM. In the BCLP group, qualitative synthesis suggested similar changes in alveolar, lip, and nasal dimensions with dNAM and cNAM. In both cleft groups (UCLP, BCLP), reduced alveolar cleft width was observed in the dNAM group compared to the non-presurgical intervention protocol, along with fewer clinical visits and reduced chairside time for dNAM compared to cNAM. It can be concluded that the treatment outcomes with dNAM were comparable to cNAM in reducing malformation severity and were advantageous in terms of chairside time and clinical visit frequency. However, the overall quality of evidence is very low and standardization is needed for the virtual workflow regarding the alveolar movements and growth factor algorithms. Registration: PROSPERO-database (CRD42020186452).

Customized planning of the visible maxillary arch width in harmony with interparopia width and smile width for female facial aesthetics.

BACKGROUND: The visible maxillary arch width (VAW) is an important aesthetic-determining feature. To date, there is no well-established methodology to determine the aesthetically optimal VAW in customized treatment planning. METHODS: In this study, the common traits of the dentofacial configuration were investigated in most attractive Asian and Caucasian female smiles. The smiling photo of a subject was digitally modified based on combined variations of VAW, smile width (SW), transverse facial dimensions (TFD), and vertical facial dimensions. These modified photos were assessed for aesthetics. The aesthetically essential parameters were identified, and their mathematic correlations and reference ranges were determined for different vertical facial patterns. Using the obtained results, a mathematic guidance was constructed for customized smile designing. The applicability of this guidance was tested in Asian females. RESULTS: The most attractive Asian and Caucasian female smiles have intraracial and interracial commonalities in the VAW-to-TFD ratios. The interparopia width (IPD) predominated over facial widths in determining well-matched VAW and SW. For optimal smile aesthetics, the VAW and SW were correlated as simulated by the formula 1.92 IPD ≤ VAW + 2.3 SW ≤ 2.17 IPD, plus the VAW-to-IPD ratio within 0.54 to 0.62 and the SW-to-IPD ratio within 0.61 to 0.71, ranges tailored to vertical facial patterns. This constitutes a mathematic guidance for customized planning of the aesthetically optimal VAW. This guidance was preliminarily validated to be applicable to Asian females. CONCLUSIONS: The VAW-to-TFD ratios were essential for Caucasian and Asian female smile aesthetics. The mathematic guidance could serve as a reference for customized smile designs for Asian females.

Mycobacterial and Plasmodium ovale-associated destruction of the jaw bones.

OBJECTIVES: The project aims were to identify infectious mechanisms responsible for an extreme form of mandibular osteonecrosis and osteomyelitis in West African populations and test the hypothesis that Mycobacterium tuberculosis plays a pivotal role. MATERIALS AND METHODS: DNA was extracted from mandibular fragments of 9 of 19 patients previously included in a prospective study leading to the mycobacterial hypothesis. Amplified DNAs were used for preparing libraries suitable for next-generation sequencing. For comparison of the whole-genome sequencing data of the 9 patients with DNAs of both microbiota and human tissues, DIAMOND v0.9.26 was used to align sequencing reads to NCBI-nr database and MEGAN 6 for taxonomy binning and identification of Mycobacterium tuberculosis strains. RESULTS: The data show that mandibular bone fragments of all 9 patients not only contain Homo sapiens and Mycobacterium tuberculosis DNAs; they also contain DNAs of Plasmodium ovale wallikeri, Staphylococcus aureus, Staphylococcus hominis, and Prevotella P3-120/intermedia; as well as large numbers of DNAs from other infectious components. CONCLUSIONS: The data obtained provide direct evidence to support the conclusion that combinations of Mycobacterium tuberculosis, Plasmodium ovale wallikeri, and other oral bacteria are involved in this particular type of mandibular destruction in West African individuals of many ages.

Nonuniformity in ligaments is a structural strategy for optimizing functionality.

Ligaments serve as compliant connectors between hard tissues. In that role, they function under various load regimes and directions. The 3D structure of ligaments is considered to form as a uniform entity that changes due to function. The periodontal ligament (PDL) connects the tooth to the bone and sustains different types of loads in various directions. Using the PDL as a model, employing a fabricated motorized setup in a microCT, we demonstrate that the fibrous network structure within the PDL is not uniform, even before the tooth becomes functional. Utilizing morphological automated segmentation methods, directionality analysis, as well as second harmonic generation imaging, we find high correlation between blood vessel distribution and fiber density. We also show a structural feature in a form of a dense collar around the neck of the tooth as well as a preferred direction of the fibrous network. Finally, we show that the PDL develops as a nonuniform structure, with an architecture designed to sustain specific types of load in designated areas. Based on these findings, we propose that ligaments in general should be regarded as nonuniform entities, structured already at developmental stages for optimal functioning under variable load regimes.

Osteoblast autophagy in glucocorticoid-induced osteoporosis.

Administration of glucocorticoids is an effective strategy for treating many inflammatory and autoimmune diseases. However, glucocorticoid treatment can have adverse effects on bone, leading to glucocorticoid-induced osteoporosis (GIO), the most common form of secondary osteoporosis. Although the pathogenesis of GIO has been studied for decades, over the past ten years the autophagy machinery has been implicated as a novel mechanism. Autophagy in osteoblasts, osteocytes, and osteoclasts plays a critical role in the maintenance of bone homeostasis. Herein, we specifically discuss how osteoblast autophagy responds to glucocorticoids and its role in the development of GIO.

YAP regulates periodontal ligament cell differentiation into myofibroblast interacted with RhoA/ROCK pathway.

During orthodontic tooth movement (OTM), periodontal ligament cells (PDLCs) receive the mechanical stimuli and transform it into myofibroblasts (Mfbs). Indeed, previous studies have demonstrated that mechanical stimuli can promote the expression of Mfb marker α-smooth muscle actin (α-SMA) in PDLCs. Transforming growth factor ß1 (TGF-ß1), as the target gene of yes-associated protein (YAP), has been proven to be involved in this process. Here, we sought to assess the role of YAP in Mfbs differentiation from PDLCs. The time-course expression of YAP and α-SMA was manifested in OTM model in vivo as well as under tensional stimuli in vitro. Inhibition of RhoA/Rho-associated kinase (ROCK) pathway using Y27632 significantly reduced tension-induced Mfb differentiation and YAP expression. Moreover, overexpression of YAP with lentiviral transfection in PDLCs rescued the repression effect of Mfb differentiation induced by Y27632. These data together suggest a crucial role of YAP in regulating tension-induced Mfb differentiation from PDLC interacted with RhoA/ROCK pathway.

Glucosamine oral administration as an adjunct to hyaluronic acid injection in treating temporomandibular joint osteoarthritis.

OBJECTIVE: To investigate the therapeutic effect of oral glucosamine (GS) as an adjunct to hyaluronic acid (HA) injection on patients with temporomandibular joint osteoarthritis (TMJ OA). METHODS: In this clinical trial, 136 participants, diagnosed as TMJ OA clinically and radiographically, were enrolled and randomized into two groups (group GS + HA: oral GS + HA injection; group placebo + HA: oral placebo + HA injection). Pain, maximum interincisal mouth opening (MMO), the levels of IL-1ß, IL-6, and TGF-ß in TMJ synovial were defined as the outcome measurements and conducted before operation, and at 1-month and 1-year follow-up. RESULTS: In both groups, pain scores were decreased and MMOs were increased at 1-month and 1-year follow-up, the changes at 1-year follow-up showed statistically significant intergroup differences. At 1-month follow-up, only IL-6 concentration was lower in group GS + HA than that in group placebo + HA. One year later, TGF-ß concentration was higher and IL-6 and IL-1ß concentrations were lower in group GS + HA than those in group placebo + HA. CONCLUSIONS: Both strategies alleviated symptoms in short term, but the patients treated with GS benefited more than those with placebo in long term, which may be due to the suppression of IL-1ß and IL-6 and the stimulation of TGF-ß.

Effects of TGF-ß1 on OPG/RANKL expression of cementoblasts and osteoblasts are similar without stress but different with mechanical compressive stress.

INTRODUCTION: This study aimed to explore the effects of TGF-ß1 on regulating activities of cementoblasts and osteoblasts with or without stress. MATERIAL AND METHODS: Human recombinant TGF-ß1 was added with different doses. Immunohistochemical test of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL) and Alizarin Red-S staining were conducted. Mechanical compressive stress was obtained by increasing the pressure of gaseous phase. OPG/RANKL expression was detected in both cells through quantitative real-time PCR. RESULTS: Similar significant differences (P < 0.05) existed in OPG/RANKL change with increasing concentration of TGF-ß1 without mechanical stress for cementoblasts and osteoblasts. However, under 3 h stress, OPG increased and RANKL decreased significantly (P < 0.01) but with similar OPG/RANKL change. Moreover, under 24 h stress, OPG change exhibited no difference (P > 0.05), but RANKL decreased significantly (P < 0.01) at 10 and 100 ng/mL TGF-ß1 in cementoblasts. In osteoblasts, OPG increased significantly (P < 0.01) at 10 and 100 ng/mL, whereas RANKL decreased with statistical difference (P < 0.05) at 1 and 10 ng/mL. CONCLUSIONS: The effects of TGF-ß1 on OPG/RANKL expression of cementoblasts and osteoblasts are similar even without mechanical stress. However, these effects are different under mechanical compressive stress.

Role of sagittal and oblique smiling profiles in evaluating facial esthetics.

INTRODUCTION: Surgeons and orthodontists used to use a conventional set of facial photographs, composed of front, front smiling, and profile images to evaluate facial esthetics, whereas sagittal and oblique smiling profile images have been largely neglected in practice. The aim of this study was to explore the importance of sagittal and oblique smiling profiles in evaluating facial esthetics. METHODS: Photographs from 80 patients, of whom 40 underwent orthognathic surgery and 40 underwent orthodontic treatment, including front, front smiling, profile, sagittal profile smiling, and oblique profile smiling images before and after treatment, were collected and synthesized into 6 categories. Thirty judges gave scores to these photographs based on their own esthetic conception with a 1-week interval for each category. RESULTS: The results demonstrated that the mean score change of evaluating facial attractiveness of patients who underwent orthognathic surgery was lower when adding sagittal or oblique smiling profiles before the treatment, whereas it was higher after the treatment, which were opposite to the orthodontic treatment group with a higher score before the treatment and a lower score after the treatment when sagittal or oblique smiling profiles were added. The changes have a significant difference in adding both sagittal smiling profiles (P < 0.05) and oblique smiling profiles (P < 0.05) before and after treatment. CONCLUSIONS: Along with oblique smiling profile, sagittal smiling profile is crucial in evaluating facial esthetics for orthodontic treatment and orthognathic surgery. Both of them suggested to be integrated in routine photographic assessment of facial attractiveness evaluation before and after treatment, especially in orthognathic surgery for facial esthetic evaluation.

Effect of mesiodistal angulation of the maxillary central incisors on esthetic perceptions of the smile in the frontal view.

INTRODUCTION: The purpose of this study was to analyze the effect of mesiodistal angulation of the maxillary central incisors on the smiling esthetics in young adults. METHODS: Frontal smile photographs of a young man and a young woman were digitally modified to produce 28 smile images that were grouped into 4 series. These images were judged using visual analog scales by 52 orthodontists and 61 laypeople. The effects of the judges' professions, subjects' sexes, and photograph framings on the appreciation of smile esthetics with different mesiodistal angulations of the maxillary central incisors were evaluated. The data were analyzed with paired t tests, Dunnett t tests, and independent samples t tests; statistical significance was set at P <0.05. RESULTS: The images were ranked less attractive as the mesiodistal angulation of the maxillary central incisors increased during smiling. No relationship was found between the judges' professions and the esthetic evaluations of incisal angulation, but the statistical analysis showed that both the subject's sex and the photograph framing were significant variables (P <0.05). CONCLUSIONS: The mesiodistal angulation of the maxillary central incisors plays an essential role in smile esthetics in the frontal view. When formulating treatment plans, orthodontists should never underestimate the influence of mesiodistal angulation on smile attractiveness.

Efficacy and safety of mepivacaine compared with lidocaine in local anaesthesia in dentistry: a meta-analysis of randomised controlled trials.

The objective of the study was to assess the efficacy and safety of mepivacaine compared with lidocaine used in local anaesthesia in dentistry. Medline, Cochrane Central Register of Controlled Trials, EMBASE, Chinese BioMedical Literature Database, China National Knowledge Infrastructure and WHO International Clinical Trials Registry Platform were searched electronically. Relevant journals and references of studies included were hand-searched for randomised controlled trials comparing mepivacaine with lidocaine in terms of efficacy and safety. Twenty-eight studies were included, of which 15 had low risk of bias and 13 had moderate risk of bias. In comparison with 2% lidocaine with 1:100,000 adrenaline, 3% mepivacaine showed a lower success rate (P = 0.05), a shorter onset time of pulpal anaesthesia (P = 0.0005), inferior pain control during injection phase and superior inhibition of heart rate increase (P < 0.0001). In contrast, 2% mepivacaine with 1:100,000 adrenaline gave a higher success rate (P < 0.00001), a similar onset time of pulpal anaesthesia (P = 0.34) and superior pain control during injection phase (P < 0.0001); 2% mepivacaine with 1:20,000 levonordefrin had the same success rate (P = 0.69) and similar onset time of pulpal anaesthesia (P = 0.90). In addition, 3% mepivacaine had shorter onset time (P = 0.004), same level of success rate (P = 0.28) and similar pain control during injection and postinjection compared with 2% lidocaine with 1:50,000 adrenaline. Given the efficacy and safety of the two solutions, 2% mepivacaine with vasoconstrictors is better than 2% lidocaine with vasoconstrictors in dental treatment. Meanwhile, 3% plain mepivacaine is better for patients with cardiac diseases.

Treatment effectiveness of Fränkel function regulator on the Class III malocclusion: a systematic review and meta-analysis.

INTRODUCTION: The Fränkel function regulator III appliance (FR-3) has been used to correct Class III malocclusions for many years; however, its treatment effectiveness is controversial. In this study, we aimed to assess the effectiveness of the FR-3 in treating patients with Class III malocclusion in the growth and development period. METHODS: Medline (via PubMed), Cochrane Central Register of Controlled Trials, Embase, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Scirus, Lilacs, Scopus, and World Health Organization International Clinical Trials Registry Platform were searched electronically. Relevant journals and reference lists of included studies were manually searched. The quality of the included studies was assessed with the Newcastle-Ottawa scale. The meta-analysis was carried out using RevMan (version 5.2; Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark). RESULTS: Seven high-quality cohort studies were included. The meta-analysis showed that SNA changes did not differ in the short (mean difference, 0.43°; 95% CI, -0.52°-1.39°) and long (mean difference, 0.37°; 95% CI, -0.29°-1.03°) terms. However, SNB changes significantly differed in the short (mean difference, -1.62°; 95% CI, -2.62° to -0.62°) and long (mean difference, -1.50°; 95% CI, -2.12° to -0.88°) terms. By contrast, MPA changes did not differ in the short term (mean difference, 0.55°; 95% CI, -0.74°-1.84°). CONCLUSIONS: Clinical evidence suggests that the FR-3 might restrict mandibular growth but not stimulate forward movement of the maxilla. Further high-quality studies are necessary to confirm the effectiveness of the FR-3.

Harmonizing soft tissue subnasale and chin position in a forehead-based framework: interracial commonalities and differences between Asian and Caucasian females.

OBJECTIVES: To establish a reference system for assessing the anteroposterior (A-P) position of the subnasal and lower-facial soft tissues for whole facial harmony. MATERIALS AND METHODS: Forty Asian and 40 Caucasian females with attractive profiles were selected as the "attractive" samples, with "ordinary" samples for comparison. Each profile was analyzed, and comparisons were made to reveal the interracial commonalities and differences. Esthetically essential parameters were established. An averaged attractive profile for each race was created by digital morphing and then modified into 30 variations based on combined variations of the esthetically essential parameters. Assessments were performed to investigate the esthetic ranges. RESULTS: A-P position of the subnasal and lower-facial landmarks harmonized with the forehead for female profile esthetics. In addition to balanced soft tissue subnasale (sSn)- and soft titssue pogonion (Pos)-to-forehead A-P relations, harmonizing lower-facial soft tissues to sSn was indispensable for profile attractiveness. sSn-to-glabella, Pos-to-glabella, and Pos-to-sSn A-P relations were esthetically essential. Perceived by orthodontists, the attractive Asian female profiles had sSn-to-glabella A-P relations ranging from 0.5 mm to 4.5 mm, Pos-to-sSn from -9.0 mm to -5.5 mm, and Pos-to-glabella from -8.5 mm to -1.0 mm. Compared with Asians, the attractive Caucasian female profiles had more anteriorly and widely distributed sSn relative to the forehead, wider ranges of Pos-to-sSn A-P relations, and more prominent chins. CONCLUSIONS: A reference system comprising sSn-glabella, Pos-sSn, and Pos-glabella horizontal distances was constructed for facial profile analysis. This system could aid treatment planning for surgical or orthopedic repositioning of the maxilla and chin.

Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a frequent urological malignancy characterized by a high rate of metastasis and lethality. The treatment strategy for advanced RCC has moved through multiple iterations over the past three decades. Initially, cytokine treatment was the only systemic treatment option for patients with RCC. With the development of medicine, antiangiogenic agents targeting vascular endothelial growth factor and mammalian target of rapamycin and immunotherapy, immune checkpoint inhibitors (ICIs) have emerged and received several achievements in the therapeutics of advanced RCC. However, ICIs have still not brought completely satisfactory results due to drug resistance and undesirable side effects. For the past years, the interests form researchers have been attracted by the combination of ICIs and targeted therapy for advanced RCC and the angiogenesis and immunogenic tumor microenvironmental variations in RCC. Therefore, we emphasize the potential principle and the clinical progress of ICIs combined with targeted treatment of advanced RCC, and summarize the future direction.

Graft for prevention of Frey syndrome after parotidectomy: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To detect the effect and safety of different types of grafts for the prevention of Frey syndrome after parotidectomy. MATERIALS AND METHODS: The following data bases were searched electronically: MEDLINE (using OVID, from 1948 to July 2011), Cochrane Central Register of Controlled Trials (CENTRAL, issue 2, 2011), EMBASE (available from: http://embase.com, 1984 to July 2011), World Health Organization International Clinical Trials Registry Platform (July 2011), Chinese BioMedical Literature Database (1978 to July 2011), and the China National Knowledge Infrastructure (1994 to July 2011). The relevant journals and reference lists of the included studies were manually searched for randomized controlled trials studying the effect and safety of different types of grafts for preventing Frey syndrome after parotidectomy. The risk of bias assessment using Cochrane Collaboration's tool and data extraction was independently performed by 2 reviewers. The meta-analysis was performed using Review Manager, version 5.1. RESULTS: A total of 14 randomized clinical trials and 1,098 participants were included. All had an unclear risk of bias. The meta-analysis results showed that the use of an acellular dermis matrix can reduce by 82% the risk of Frey syndrome compared with the no-graft group using an objective assessment (relative risk [RR] 0.18, 95% confidence interval [CI] 0.12 to 0.26; P < .00001; Grading of Recommendations, Assessment, Development, and Evaluation [GRADE] quality of evidence: high). The acellular dermis matrix can also reduce by 90% the risk of Frey syndrome compared with the no-graft group using a subjective assessment (RR 0.10, 95% CI 0.05 to 0.22; P < .00001; GRADE quality of evidence: high). The muscle flaps can reduce by 81% the risk of Frey syndrome compared with the no-graft group (RR 0.19, 95% CI 0.13 to 0.27; P < .00001; GRADE quality of evidence: high). No statistically significant difference was found between the acellular dermal matrix and muscle flap groups (RR 0.73, 95% CI 0.15 to 3.53, P = .70; GRADE quality of evidence: low). No serious adverse events were reported. CONCLUSIONS: The present clinical evidence suggests that grafts are effective in preventing Frey syndrome after parotidectomy. More randomized clinical trials are needed to confirm our conclusions and prove the safety of the grafts.

Ultrasonography for detection of disc displacement of temporomandibular joint: a systematic review and meta-analysis.

PURPOSE: To assess the diagnostic efficacy of ultrasonography in detecting disc displacement of the temporomandibular joint. MATERIALS AND METHODS: MEDLINE (using OVID, 1950 to April 2011), EMBASE (1980 to April 2011), and the Chinese Biomedical Literature Database (1978 to April 2011) were searched electronically. In addition, relevant journals and reference lists of the included studies were manually searched for any eligible studies on diagnostic accuracy. Two authors performed the study inclusion, data extraction, and risk of bias assessment in duplicate. Meta-analysis was performed with MetaDisc 1.4. RESULTS: Fifteen studies were included in this meta-analysis; 6 studies had a low risk of bias, 6 studies an unclear risk, and 3 studies a high risk. Meta-regression indicated that the detected results were not influenced by the types of ultrasonography, image dimensions, types of transducer, and ultrasonic image of the disc (P > .05). The Q* values of ultrasonography for the closed- and open-mouth positions were 0.79 and 0.91, respectively. The diagnostic efficacy of disc displacement with reduction had a sensitivity of 0.76, a specificity of 0.82, a positive likelihood ratio of 3.80, a negative likelihood ratio of 0.36, a diagnostic odds ratio of 10.95, an area under the curve of 0.83, and a Q* of 0.76. The diagnostic efficacy of disc displacement without reduction had a sensitivity of 0.79, a specificity of 0.91, a positive likelihood ratio of 80.5, a negative likelihood ratio of 0.25, diagnostic odds ratio of 36.80, an area under the curve of 0.97, and a Q* of 0.92. CONCLUSIONS: The diagnostic efficacy of ultrasonography is acceptable and can be used as a rapid preliminary diagnostic method to exclude some clinical suspicions. However, positive ultrasonographic findings should be confirmed by magnetic resonance imaging. Also, the ability of ultrasonography to detect lateral and posterior displacements is still unclear. More high-quality studies are needed to assess the diagnostic efficacies of some specific ultrasonographic methods. Standards and criteria for ultrasonographic techniques in the diagnosis of disc displacement should be established in the future.

Inclination of the osseous components of the temporomandibular joint related with disc displacement: Magnetic resonance and cone beam computed tomography imaging-based study.

OBJECTIVE: To assess the association between three-dimensional inclination of the osseous structures of temporomandibular joints (TMJ) and the risk of disc displacement (DD). METHODS: The 120 TMJs of 60 patients were evaluated. According to magnetic resonance images, disc position was classified as normal, anterior DD with reduction (ADDWR) and without reduction (ADDWoR) and as normal, medial DD (MDD), and lateral DD (LDD) on the sagittal and coronal views, respectively. Condyle and eminence inclinations were measured using cone beam computed tomography. RESULTS: Smaller horizontal condylar inclination was associated with ADDWoR (p < 0.05). Larger coronal condylar inclination was associated with ADDWR (p < 0.05) and LDD (p < 0.05). There was no association between sagittal eminence inclination and DD (p < 0.05). CONCLUSION: Medial condylar rotation in the axial view may be associated with ADDWoR. The condyle head horizontally inclined in the coronal view may be associated with ADDWR and LDD.

Electroactive composite scaffold with locally expressed osteoinductive factor for synergistic bone repair upon electrical stimulation.

Tissue engineering is a promising strategy for the repair of large-scale bone defects, in which scaffolds and growth factors are two critical issues influencing the efficacy of bone regeneration. Unfortunately, the broad application of growth factors is limited by their poor stability in the scaffolds. In the present study, the strictly controlled expression of human bone morphogenetic protein-4 (hBMP-4) in the presence of doxycycline is achieved by adding an hBMP-4 gene fragment into a non-viral artificial restructuring plasmid vector (pSTAR) to form the pSTAR-hBMP-4 plasmid (phBMP-4). Furthermore, the controlled release of phBMP-4 is obtained with an electroactive tissue engineering scaffold, generated by combining a triblock copolymer of poly(l-lactic acid)-block-aniline pentamer-block-poly(l-lactic acid) (PLA-AP) with poly(lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA). This PLGA/HA/PLA-AP/phBMP-4 composite scaffold, with controlled gene release and Dox-regulated gene expression upon electrical stimulation, operating synergistically, exhibits an improved cell proliferation ability, enhanced osteogenesis differentiation in vitro, and effective bone healing in vivo in a rabbit radial defect model. Taking these results together, the proposed smart PLGA/HA/PLA-AP/phBMP-4 scaffold lays a solid theoretical and experimental basis for future applications of such multi-functional materials in bone tissue engineering to help patients in need.