低强度脉冲超声在颌骨牵张成骨中的应用

在颌骨牵张成骨中,缩短治疗时间和促进新骨形成以及设计理想的牵张器一直是研究的热点.超声以其独特的理化性质和生物学作用在医学领域有广泛的应用,尤其是低强度脉冲超声在促进骨愈合中显示出了巨大的潜力,已有学者将其用于牵张成骨中.低强度脉冲超声能促进新骨生成,加快骨组织愈合,缩短治疗时间,减少牵张成骨术的并发症.本文就低强度脉冲超声在颌骨牵张成骨中的作用及其机制作一综述.     

The osteogenic activity of human mandibular fracture haematoma-derived cells is stimulated by low-intensity pulsed ultrasound in vitro

Low intensity pulsed ultrasound (LIPUS) stimulation is a clinically established treatment method used to accelerate long bone fracture healing; however, this method is currently not applied to mandibular fractures. In this study, we investigated the effects of LIPUS on human mandibular fracture haematoma-derived cells (MHCs) in order to explore the possibility of applying LIPUS treatment to mandibular fractures. MHCs were isolated from five patients. The cells were divided into two groups: (1) LIPUS (+) group: MHCs cultured in osteogenic medium with LIPUS treatment; and (2) LIPUS (−) group: MHCs cultured in osteogenic medium without LIPUS treatment. The osteogenic differentiation potential and proliferation of the MHCs were compared between the two groups. The waveform used was equal to the wave conditions of a clinical fracture healing system. The gene expression levels of ALP, OC, Runx2, OSX, OPN, and PTH-R1 and mineralization were increased in the LIPUS (+) group compared to the LIPUS (−) group. There were no significant differences in cell proliferation between the two groups. These findings demonstrate the significant effects of LIPUS on the osteogenic differentiation of MHCs. This study provides significant evidence for the potential usefulness of the clinical application of LIPUS to accelerate mandibular fracture healing.     

低强度脉冲超声在牙周组织再生中的作用

牙周病、根面龋以及颌面先天畸形和创伤等都会不同程度地导致牙槽骨、牙龈和牙周膜等牙周支持组织缺损。低强度脉冲超声（LIPUS）的温热效应和机械刺激可促进成骨质细胞、成牙本质细胞和牙周膜细胞（PDLC）的生成和分化。PDLC可分化成中胚层细胞谱系,进而生成牙槽骨、牙骨质和牙周膜等牙周组织。碱性磷酸酶（AKP）和骨钙蛋白（OCN）为骨形成或骨分化的晚期标志物,经LIPUS刺激过的PDLC,其AKP活性和OCN的表达皆提高。经LIPUS刺激可减少正畸过程中牙根的吸收,促进修复牙根缺损的成牙骨质细胞的增殖分化和矿化,促进牙周组织伤口愈合和血管生成的结缔组织生长因子的表达,从而加速牙周软组织的愈合。LIPUS刺激在牙周支持组织再生中为一种安全无创的治疗手段,但其最佳刺激强度和治疗时间尚需继续探索。     

低强度脉冲超声波联合引导骨组织再生促进牙周骨缺损修复的实验研究

目的探讨低强度脉冲超声波（LIPUS）联合引导骨组织再生（GBR）对Beagle犬尖牙牙周骨缺损的修复效应。方法将8只Beagle犬中每只犬的4颗尖牙随机分配到4组：实验1组（LIPUS处理+GBR+自体骨移植组）,实验2组（LIPUS处理+自体骨移植组）,实验3组（GBR+自体骨移植组）,空白对照组。在犬尖牙颊侧区根中1/3处制备牙周骨缺损模型,根据分组,自体骨移植后,实验1组和2组采用LIPUS处理20 min·d-1,超声强度为30 mW·cm-2,实验1、3组植入Bio-Gide胶原膜。在LIPUS处理6、8周后处死Beagle犬,对各组尖牙牙周骨缺损区进行Micro-CT检测和分析。结果临床观察各组牙周骨缺损面积均不同程度缩小。Micro-CT检测分析表明,各组6周与8周时的骨小梁数目、骨小梁厚度和骨小梁体积均无统计学差异（P＞0.05）,而各组之间的骨组织测量指标均有统计学差异（P＜0.05）,实验1组新生骨量最多。结论LIPUS具有促进牙周骨缺损修复的潜能,LIPUS与GBR结合可能更有利于牙周骨缺损的修复与再生。     

The role of Vitamin D as an adjunct for bone regeneration: A systematic review of literature

Background and objectivesIn spite of bone’s healing capacity, critical-size bone defect regeneration and peri-implant osseointegration are challenging. Tissue engineering provides better outcomes, but requires expensive adjuncts like stem cells, growth factors and bone morphogenic proteins. Vitamin D (Vit.D) regulates calcium and phosphorus metabolism, and helps maintain bone health. Vit.D supplements in deficient patients, accentuates bone healing and regeneration. Therefore the aim of this systematic review was to evaluate the role of adjunctive Vit.D on bone defect regeneration.MethodsComprehensive database search of indexed literature, published between January 1990 and June 2022, was carried out. English language articles fulfilling inclusion criteria (clinical/in vivo studies evaluating bone regeneration including osseointegration and in vitro studies assessing osteogenic differentiation, with adjunct Vit.D) were identified and screened.ResultsDatabase search identified 384 titles. After sequential title, abstract and full-text screening, 23 studies (in vitro – 9/in vivo – 14) were selected for review. Vit.D as an adjunct with stem cells and osteoblasts resulted in enhanced osteogenic differentiation and upregulation of genes coding for bone matrix proteins and alkaline phosphatase. When used in vivo, Vit.D resulted in early and increased new bone formation and mineralization within osseous defects, and better bone implant contact and osseointegration, around implants. Adjunct Vit.D in animals with induced systemic illnesses resulted in bone defect regeneration and osseointegration comparable to healthy animals. While systemic and local administration of Vit.D resulted in enhanced bone defect healing, outcomes were superior with systemic route.ConclusionsBased on this review, adjunct Vit.D enhances bone defect regeneration and osseointegration. In vitro application of Vit.D to stem cells and osteoblasts enhances osteogenic differentiation. Vit.D is a potentially non-invasive and inexpensive adjunct for clinical bone regeneration and osseointegration. Long term clinical trials are recommended to establish protocols relating to type, dosage, frequency, duration and route of administration.     

The effects of low-intensity pulsed ultrasound exposure on gingival cells

Background: Low‐intensity pulsed ultrasound (LIPUS) has been used in fracture treatment to shorten the time needed for biologic wound healing. Clinical trials applying LIPUS in implant dentistry have reported accelerated soft‐tissue healing and osseointegration. However, details of the clinical effects of LIPUS have not been well characterized. Connective tissue growth factor (CCN2/CTGF) plays an important role in wound healing and angiogenesis in periodontal tissue. In this study, we focus on the effect of LIPUS on gingival epithelial cells and the role of CCN2/CTGF therein. Methods: Gingival epithelial cells (GE1) were cultured in six‐well cell‐culture plates for 24 hours at 37°C with 5% CO₂, and then exposed to LIPUS for 15 minutes at 3‐MHz frequency and 40‐mW/cm² power. Total RNA was extracted after LIPUS exposure and analyzed by real‐time polymerase chain reaction to detect CCN2/CTGF. Additionally, total protein from each sample after LIPUS exposure was immunoblotted with anti‐CCN2/CTGF antibody. Results: LIPUS exposure increased the mRNA level of CCN2/CTGF on exposure, and the level was significantly greater at 0 and 15 minutes after LIPUS exposure compared to the control. Western blotting analysis showed intense staining of CCN2/CTGF for 60 minutes after LIPUS exposure. The results demonstrate that LIPUS exposure accelerates soft‐tissue healing by increasing CCN2/CTGF on exposure, in addition to its effects on bone formation. Conclusion: Our findings demonstrate that LIPUS exposure accelerates soft‐tissue healing by increasing connective tissue growth factors via a mitogen‐activated protein kinase signaling pathway on exposure.     

低强度脉冲超声波联合引导组织再生术促进牙周骨开窗缺损修复的动物实验

目的 探讨低强度脉冲超声波(low intensity pulsed ultrasound,LIPUS)联合引导组织再生术(guided tissue regeneration,GTR)对Beagle犬尖牙牙周骨开窗缺损的修复效应.方法 构建4只Beagle犬尖牙颊侧区根中1/3处牙周骨开窗缺损模型.将4只Beagle犬的16颗双侧上、下颌尖牙(实验牙)按简单随机法平均分配为4组:①实验1组,LIPUS(60 mW/cm2,20 min/d)处理+GTR+牙周骨质缺损组;②实验2组,LIPUS(60 mW/cm2,20 min/d)处理+牙周骨质缺损组;③实验3组,GTR+牙周骨质缺损组;④空白对照组,牙周骨质缺损组.实验共进行28 d.每14天分别测量各组处理前后实验牙牙龈表面温度,并行Wilcoxon符号秩和检验.4周后观察脱钙骨组织切片,分析各组尖牙牙周骨开窗缺损的组织学修复效果.结果 临床观察各组实验牙牙周均愈合良好.各组处理前后的牙龈表面温度差值[M(Q)]分别为:实验1组:0.225(0.463)℃;实验2组:0.265(0.133)℃;实验3组:0.09(0.115)℃;空白对照组:-0.175(0.370)℃,实验1、2组每次处理前后温度变化差异均有统计学意义(P值均为0.027).脱钙骨组织切片观察显示实验1组骨缺损内充满团状新生骨组织,成骨细胞增生活跃,骨胶原较成熟,Masson染色红染明显;实验3组新生牙骨质、牙槽骨较实验2组和空白对照组多,新生骨胶原成熟度不高,Masson染色呈红蓝相间;实验2组新生骨胶原成熟度较实验3组和空白对照组高,Masson染色红染明显;空白对照组可见少量新生牙骨质沿切迹处生长,新生骨胶原不成熟,Masson染色呈红蓝相间.结论 LIPUS具有促进牙周骨开窗缺损修复的潜能,LIPUS与GTR结合可能更利于牙周组织缺损的修复.

Abstract：

Objective To evaluate the effects of low intensity pulsed ultrasound(LIPUS)combined with guided tissue regeneration(GTR) for the repair of the periodontal fenestration defect at the canines in Beagle dogs. Methods Four Beagle dogs were used for establishing the periodontal fenestration defect. Sixteen canines of four Beagle dogs were simple randomly assigned into experimental group 1[LIPUS(60 mW/cm2,20 min/d)irradiation + GTR + the periodontal fenestration defect], experimental group 2[LIPUS(60 mW/cm2,20 min/d)irradiation + the periodontal fenestration defect], experimental group 3(GTR+ the periodontal fenestration defect) and control group(the periodontal fenestration defect). Experiments conducted 28 d. The temperature of the gingive′s surface of each group was tested every 14 days(analyzed by Wilcoxon rank sum test with SPSS 13.0). The demineralized bone tissue slices of the periodontal fenestration were obtained for histologic staining after 4 weeks treatment. Results Clinically all the treatment groups healed well. The change of gingive′s surface temperature[M(Q)] before and after LIPUS irradiating were:0.225(0.463)℃(experimental group 1),0.265(0.133)℃ (experimental group 2),0.090(0.115)℃(experimental group 3);-0.175(0.370)℃(control group). The P value of experimental group 1 and 2 with pre-and post-treatment each time were both 0.027. Histology of the demineralized bone tissue revealed that in experimental group 1, the bone defect was filled with fresh bone-like tissues, proliferatively active osteoblasts and newly formed cementum-like tissues along the defect surface. In experimental group 3, there were more new cementum-and bone-like tissues than in experimental group 2 and control group. In experimental group 2,the new bone collagen was more mature than in experimental group 3 and control group. In control group,there was less growth of new cementum along the notch, and the new bone collagen was immature. Conclusions LIPUS combined with GTR may have the potential of promoting the repair of periodontal fenestration defect.     

Underlying mechanisms at the bone-surface interface during regeneration

The goal of regenerative therapy around teeth and implants is to create a suitable environment in which the natural biological potential for functional regeneration of periodontal ligament and/or bone can be maximized. In order for the regenerative process to be successful, the following factors must be addressed: prevention of acute inflammation from bacteria, mechanical stability of the wound, creation and maintenance of blood clot-filled space, isolation of the regenerative space from undesirable competing tissue types, and the creation of a desirable surface chemistry, energy, roughness and microtopography that can directly influence cellular response, ultimately affecting the rate and quality of new tissue formation and, therefore, the regeneration process. This paper will review how surface characteristics (chemistry and roughness) can affect cell response and local factor production. To evaluate the effect of surface chemistry on cell proliferation and differentiation costochondral chondrocytes were grown on standard tissue culture plastic dishes sputter-coated with different materials. The results indicate that surface materials can elicit differential responses in cell metabolism and phenotypic expression in vitro. In a second study, the effect of varying titanium surface roughnesses on osteoblast-like cell behavior was examined. Surface roughness was found to alter osteoblast proliferation, differentiation and matrix production in vitro. In addition, production of PGE₂ and TGFβ by these cells was also shown to increase with increasing surface roughness, indicating that substrate surface roughness also affects cytokine and growth factor production. The role of surface roughness in determining cellular response was further explored by comparing the response of osteoblasts grown on new and previously used surfaces. The results of these latter studies showed that cell proliferation, expression of differentiation markers and overall matrix production are not altered when cells are grown on used vs. virgin surfaces. This suggests the possibility that implants may be re-used, especially in the same patient, if they are appropriately treated. In this context, it should also be noted that rougher titanium surfaces may require more extensive cleaning procedures. From a global perspective, these studies provide some insight into how bone regeneration can be optimized in the presence of an implant or tooth root residing at the site of a bony defect. Since the new bone being produced, during regeneration, grows from a distal area toward the implant or tooth root surface, it is hypothesized that the osteoblasts growing on the surface of the implant may produce local factors that can affect the bone healing process distally. In short, it appears that the surface characteristics of an implant, particularly roughness, may direct tissue healing and, therefore, subsequent implant success in sites of regeneration by modulating osteoblast phenotypic expression.     

下颌骨骨折愈合过程中整合素β1表达的免疫组化研究

目的：探讨下颌骨骨折愈合过程中整合素β1表达水平的改变。方法：用兔下颌骨骨折的动物模型,分别于骨折前一天及骨折后第1、3、5、7、14、30、60、90天取骨断端组织标本作成石蜡切片并用LsAB法进行免疫组织化学实验,以探讨整合素β1在骨组织,特别是在成骨细胞和破骨细胞中的表达。结果：整合素β1在骨组织及其周围软组织中广泛表达;面骨细胞上的整合素β1在7d后表达增强,14－30d最为强烈,90d时接近正常。破骨细胞上整合素β1在骨折后14d表达增强,一直延续到90d。结论：在下颌骨骨折的愈合过程中,整合素β1在骨组织,特别是在成骨细胞和破骨细胞上的表达增强,整合素β1对骨折的愈合过程具有影响作用。     

Effect of low intensity pulsed ultrasound stimulation on sinus augmentation in rabbits

Objectives

The objective of the present study was to evaluate the efficacy of low intensity pulsed ultrasound stimulation (LIPUS) and to determine the optimal frequency for enhancing bone regeneration in sinus augmentation using a rabbit model.

Material and methods

Thirty male rabbits underwent sinus augmentation. Two rectangular nasal bone windows were outlined bilaterally. LIPUS was applied at two different frequencies (1 MHz and 3 MHz) on experimental sites daily for 2, 4 and 8 weeks. Each histological area of the experimental and control sites was divided into upper and lower parts from the parietal region to a depth of 5 mm. Each area of new bone was measured.

Results

At 2, 4 and 8 weeks, the experimental sites in the 1 MHz group exhibited significantly more new bone growth than the control sites in both the upper and lower parts. When the upper and lower parts of each area were measured in combination there was a statistical difference between the test and control sites in the 1 MHz group at 2, 4 and 8 weeks; however, there were no statistical differences between the test and control sites in the 3 MHz group.

Conclusions

The results suggest that clinical application of LIPUS for sinus augmentation may promote new bone formation, and that the effect of LIPUS for sinus augmentation at a frequency of 1 MHz was greater than at 3 MHz until 8 weeks after sinus augmentation.     

Plasma Rich in Growth Factors Promotes Bone Tissue Regeneration by Stimulating Proliferation,Migration, and Autocrine Secretion in Primary Human Osteoblasts

Background: Alveolar bone loss can be a major clinical concern affecting both functionality and esthetics. Osteoblasts are the main cells charged with the repair and regeneration of missing bone tissue. Plasma rich in growth factors (PRGF) allows delivery of a cocktail of proteins and growth factors that promote wound healing and tissue regeneration to the site of injury. This study tests the effect of this endogenous regenerative technology to stimulate alveolar osteoblast bone‐forming potential. Methods: Primary human osteoblasts were retrieved from alveolar bone of patients undergoing oral surgery. Cell proliferation was evaluated, and culture inserts and permeable transwell supports were used to assess cell migration and chemotaxis. The expression of differentiation markers was quantified by enzyme‐linked immunosorbent assay. Results: PRGF succeeded in increasing proliferation, migration, and chemotaxis of osteoblasts. Also, PRGF significantly enhanced the autocrine expression of two relevant proangiogenic factors, vascular endothelial growth factor and hepatocyte growth factor, and three markers of osteoblastic activity, procollagen I, osteocalcin, and alkaline phosphatase. Conclusion: The results indicate that PRGF can stimulate some of the biologic processes of the main cells responsible for bone regeneration and help support the positive clinical outcomes that have been reported with this technology.     

Treatment of an early implant failure according to the principles of guided tissue regeneration (GTR)

The present case report demonstrates the application of guided tissue regeneration (GTR) in combination with antimicrobial therapy for the treatment of an early implant failure. This treatment approach both prevented further loss of bone as well as led to the regeneration of lost bone. By means of color-converted digital subtraction images, remodelling of the tissues adjacent to the defect was documented as early as one month postsurgically. The images demonstrated "bone-fill" in the apical portion of the defect and resorptive changes at the bone crest. This case report demonstrates that combined regenerative and antimicrobial therapy may be a successful treatment approach restoring osseointegration of dental implants following loss of bone due to infection. Continuously increasing bone-fill inside the defect was documented when comparing the radiograph obtained immediately before the GTR procedure and at months 1, 2, 4, 5 and 6 of the healing period, respectively. Clinical measurement obtained at the time of the surgery and at the time of the membrane removal confirmed the radiographic evidence of bone-fill by demonstrating new tissue resistant to probing in close contact to the implant surface at the site of the previous defect. Antimicrobial therapy included an antibiotic regimen during the 1st month of healing as well as topical rinses with an antiseptic (chlorhexidine) over the entire healing period of 6 months. As a result of this treatment approach, the implant was saved and could be used as an abutment for a bridge reconstruction.     

Effect of allogeneic freeze-dried demineralized bone matrix on regeneration of alveolar bone and periodontal attachment in dogs

Abstract. This split-mouth study was designed to evaluate regeneration of alveolar bone and periodontal attachment following implantation of allogeneic. freeze-dried, demineralized bone matrix (DBM). Buccal fenestration defects (6×4 mm) were created on the maxillary canine teeth in 6 beagle dogs. DBM was implanted into one randomly selected defect in each animal. The contralateral defect served as surgical control. Tissue blocks were harvested following a 4-week healing interval and prepared for histometric analysis. DBM was discernible in all implanted defects with limited evidence of bone metabolic activity. The DBM particles appeared invested within a dense connective tissue, often in close contact to the instrumented root. Fenestration defect height averaged 3.8±0.1 and 3.7±0.3mm, total bone regeneration 0.9±0.9 and 0.4±1.2 mm, and total cementum regeneration 2.3±1.5 and 0.6±0.7 mm for DBM and control defects, respectively. Differences with regards to cementum regeneration were statistically significant ( p =0.03). In summary, the results of this study suggest that DBM implants may enhance cementum regeneration in this defect model, and that they have no apparent effect on alveolar bone regeneration. Enhanced cementum regeneration may be possibly be explained by provisions for guided tissue regeneration from the implant suppressing a significant influence of the gingival connective tissue on the healing process. Moreover, a 4-week healing interval appears insufficient for turnover of DBM.     

Bone regeneration by statin and low-intensity pulsed ultrasound (LIPUS) in rabbit nasal bone

ObjectivesTo compare bone regeneration between local implantation of statin and low-intensity pulsed ultrasound (LIPUS), and the combination of statin with LIPUS in rabbit nasal bone using histological and immunohistochemical methods.Study design: Thirty-two adult male Japanese white rabbits (age: 12–16 weeks, weight: 2.5–3.0 kg) were used in this study. Two bone circular defects (5 mm in diameter) per rabbit were created in the nasal bone while preserving the nasal membrane. The two defects in each rabbit were filled with 2.5 mg/ml simvastatin in 0.2 ml water with an atelocollagen sponge (ACS) and ACS alone respectively. Sixteen rabbits (32 sides) received the LIPUS application; the remaining 16 rabbits (32 sides) did not. Therefore, the subjects composed of 4 groups, namely, (1) LIPUS + ACS + simvastatin (the LAS group), (2) LIPUS + ACS (the LA group), (3) ACS + simvastatin (the AS group) and (4) ACS alone (the A group). Four animals were killed in each period, at 1, 2, 4 and 8 weeks postoperative. The parts that had been operated on were removed and prepared for histological assessment. The expression of BMP-2 and the bone area ratio were evaluated using histological and immunohistochemical methods.ResultsBone square in the LAS group was significantly larger than that in the AS group after 1 (P < 0.0001) and 2 week (P = 0.0113). The bone square in the LA group was significantly larger than that in the A group after 1 (P < 0.0001) and 2 weeks (P = 0.0090). However, there was no significant difference between the LAS and LA groups. In the number of cells that stained positive for BMP-2, the LAS group was significantly larger than that in the AS group after 1 (P < 0.0001) and 2 weeks (P = 0.0113).ConclusionThis study suggests that bone regeneration can be promoted by LIPUS alone and statin alone, respectively. However the combination use of LIPUS with statin does not differ from LIPUS alone or statin alone.     

截根术与引导性骨再生术结合治疗根裂牙的临床效果

目的比较单纯截根术与截根术结合引导性骨再生术5年的临床效果,以期为临床提供参考。方法选择冠修复后根裂磨牙16例,采用随机、对照的方法,实验组（10例）截根术结合引导性骨再生术治疗,对照组（6例）单纯截根术治疗。观察术前、术后患者主观感觉的变化,及出血指数、附着丧失、松动度、X线片牙槽骨高度等变化,并进行组间比较。随访5年。结果实验组术后3个月患者咀嚼力显著增加,出血指数、附着丧失、松动度、X线片牙槽骨高度等明显改善,牙槽骨高度增加（7.26±0.47）和附着获得（6.85±2.05）明显;对照组各项指标改善不明显,牙槽骨高度仍有所降低（-2.91±0.42）,出血指数无明显改善;实验组与对照组比较差异有统计学意义（P〈0.05）,且5年后仍维持不变。结论截根术结合引导性骨再生术治疗根裂牙可获得稳定的临床疗效。     

Low‐intensity pulsed ultrasound accelerates nerve regeneration following inferior alveolar nerve transection in rats

Inferior alveolar nerve (IAN) injury, which is frequently caused by orofacial surgery or trauma, induces sensory loss in orofacial regions innervated by the IAN. However, no effective treatment for orofacial sensory loss currently exists. We determined whether sensory loss in facial skin above the mental foramen following IAN transection was recovered by exposure of the transected IAN to low‐intensity pulsed ultrasound (LIPUS). Inferior alveolar nerve transection (IANX) was performed in 7‐wk‐old male Sprague‐Dawley rats. On day 7 after IANX, the effect of daily LIPUS (from day 0) on the transected IAN, in terms of sensitivity to mechanical stimulation of the facial skin above the mental foramen, was examined. Moreover, the number of trigeminal ganglion (TG) neurons innervating the facial skin above the mental foramen of rats with IANX treated daily with LIPUS was counted using the retrograde neurotracing technique. Daily exposure of the transected IAN to LIPUS significantly promoted recovery of the head‐withdrawal threshold in response to mechanical stimulation of the facial skin above the mental foramen, and the number of TG neurons innervating the facial skin above mental foramen was significantly increased in rats with IANX treated daily with LIPUS compared with sham or LIPUS‐unexposed rats. Daily treatment of stumps of the transected IAN with LIPUS facilitated morphological and functional regeneration, suggesting that LIPUS is an effective and novel therapy for IAN injury.     

Prostaglandins and bone: potential risks and benefits related to the use of nonsteroidal anti-inflammatory drugs in clinical dentistry

In the skeleton, prostaglandins, mainly PGE(2) produced by osteoblasts under COX-2 stimulation, play either a stimulatory or an inhibitory role in bone metabolism, depending on the physiological or pathological conditions. The anabolic effect occurs largely in response to mechanical forces and in bone fracture healing, whereas PGE(2)-mediated resorption contributes significantly to bone loss in inflammatory diseases and in response to prolonged immobilization. Many reports have shown that conventional nonsteroidal anti-inflammatory drugs (NSAIDs) may delay fracture healing and negatively interfere with spinal fusion in both humans and other animals, whereas the alleged inhibitory effects of COX-2-selective NSAIDs still lacks experimental and clinical evidence. Pertaining to clinical dentistry, recent studies have suggested a potential adjuvant role for NSAIDs in periodontal therapy. There are few experimental reports addressing the deleterious effects of conventional NSAIDs on alveolar bone healing; clinical reports, relating mostly to short-term administration of NSAIDs for management of post-extraction edema and pain, are just as rare and have noted no clinically perceptible delay in bone healing. Additional studies are necessary in order to elucidate whether patients who require reparational bone formation can safely receive prolonged treatment with NSAIDs, and which drug types are less harmful.     

Expression of BMP-2 and TGF-β1 mRNA during healing of the rabbit mandible

To identify the cell types which produce BMP and TGF-β during fracture healing and to elucidate the interactions between BMP and TGF-β in regulating cell proliferation and differeentiation at various stages, an experimental model of fracture healing in the rabbit mandible was established and the expression of BMP-2 and TGF-β1 mRNA was studied at different healing stages by in situ hybridization. The results showed that undifferentiated mesenchymal cells, differentiating osteoblasts and chondroblasts, had higher levels of BMP-2 mRNA at the stage of intramembranous bone formation and early chondrogenesis, while the level of TGF-β1 mRNA expression was closely associated with the active synthetic stage of osteoblasts and chondrocytes. These obserbvations suggest that both BMP and TGF-β are involved in the regulation of fracture healing, BMP may play an important role in bone induction and early chondrogenesis, while TGF-β regulates the proliferation and active synthetic ability of chondrocytes and osteoblasts.     

Cumulative effect of low-level laser therapy and low-intensity pulsed ultrasound on bone repair in rats

Many studies have assessed the effects of either low-level laser therapy (LLLT) or low-intensity pulsed ultrasound (LIPUS) on bone repair; however, an evaluation of the combination of these modalities (LLLT + LIPUS) has not yet been considered. The aim of this study was to demonstrate the effects of LLLT + LIPUS on bone repair. Male Wistar rats (n = 128; four groups of 32) were used; the animals underwent a partial tibial bone osteotomy. One group had the osteotomized limb treated with LLLT, the second group with LIPUS, and the third group with the combined treatment protocols of the LLLT and LIPUS groups; the fourth group received no further treatment (control). Each group was divided into two subgroups for assessment at two different time-points, 14 and 21 days. After the completion of treatment rats were sacrificed and the tibias submitted to a three-point bending test or to histomorphometric analysis. Histological evaluation showed increased bone trabeculae, increased vascularization, and decreased inflammation in the LLLT + LIPUS group. Mechanical evaluation revealed increased biomechanical properties including maximum force, maximum stress, and stiffness, in the LLLT + LIPUS group. Combined LLLT + LIPUS treatment enhanced bone healing both histologically and mechanically, shortening the length of the treatment period, when compared to treatment with LLLT or LIPUS alone.