Defect repair in the rat mandible with bone morphogenic protein 5 and prostaglandin E1

OBJECTIVE: To compare the osteogenic abilities of 2 growth factors (bone morphogenic protein 5 [BMP-5] and prostaglandin E1 [PGE1]) and 2 carriers (collagen/polylactic acid [PLA] and collagen/calcium hydroxyapatite cement [HAC]) in the repair of a rat mandibular body defect. DESIGN: Prospective controlled trial.Subjects Twenty-nine Sprague-Dawley rats. INTERVENTIONS: Critical size defects were created in the bilateral mandibular bodies of the rats. Each hemimandible was assigned to an experimental group. The defects were filled with PLA (group 1), PLA with BMP-5 (group 2), PLA with PGE1 (group 3), HAC (group 4), HAC with BMP-5 (group 5), or HAC with PGE1 (group 6). The control group (group 7) had unfilled defects. The animals were killed after 12 weeks, and the nondemineralized specimens were processed histologically. Stereologic techniques were used to determine the volume fractions of new bone, osteoid, marrow, remaining implant, and fibrous tissue in each defect. RESULTS: The HAC/BMP-5 group (group 5) contained significantly more new bone than the PLA/BMP-5 group (group 2) (P =.02), the HAC and HAC/PGE1 groups (groups 4 and 6) (P =.002), and the control group (group 7) (P<.01). The HAC/BMP-5 group also had less fibrous tissue than the HAC group and the HAC/PGE1 group (P<.001). Groups 5 and 6 had less fibrous tissue than group 7 (P<.01). The groups containing PGE1 demonstrated significantly more osteoid development than the other experimental groups (P<.001). CONCLUSIONS: Inclusion of BMP-5 in an implant with calcium hydroxyapatite cement resulted in the formation of significantly larger fractions of new bone and less fibrous tissue ingrowth than occurred in the other experimental groups. The presence of PGE1 resulted in larger amounts of osteoid deposition, suggesting the potential for delayed bone healing.     

Insulinlike growth factor 1- and 2-augmented collagen gel repair of facial osseous defects

BACKGROUND: Defects of the facial bone structure are common problems for the facial plastic surgeon. Native type 1 collagen gels (T1CGs) have been shown to mediate repair of facial critical-size defects in rat models. OBJECTIVE: To evaluate the efficacy of T1CG augmented with insulinlike growth factor (IGF) 1, IGF-2, and a combination of IGF-1 and IGF-2 on the repair of facial critical-size defects in a rodent model. METHODS: Twenty-four retired male breeder Sprague-Dawley rats were divided into 4 groups of 6 animals. Facial critical-size defects were created by removing the nasalis bones with a bone-cutting drill. Defects were treated with 300 pg of type 1 collagen gel (T1CG), T1CG augmented with 3 microg of IGF-1, T1CG augmented with 3 microg of IGF-2, or T1CG augmented with a combination of 3 microg of IGF-1 and 3 microg of IGF-2. After 30 days the animals were examined at necropsy with precise planimetry, histological analysis of new bone growth, and radiodensitometric analysis of bone thickness. RESULTS: Radiodensitometric measurements showed that IGF-2 augmentation resulted in greatest osseous healing, with measurements being statistically significant over those of all other groups (P< or = .03). Combination IGF-1 and IGF-2 had osseous healing that was intermediate between IGF-1 augmentation and IGF-2 augmentation alone, with measurements being statistically significant over those of unaugmented gels (P<.001) and IGF-1 augmentation (P< or = .03). Augmentation with IGF-1 resulted in healing that was significant over that of unaugmented gels (P< or = .04). CONCLUSION: Collagen gels augmented with IGF significantly enhance the osteoconductive repair of nasal critical-size defects in a rodent model, with IGF-2 showing highest efficacy.     

Immunohistochemical evidence of BMP-2, -4 and -7 activity in otospongiosis

CONCLUSION: This study is the first to show that bone morphogenetic proteins (BMP)-2, -4 and -7 play a role in active phase otosclerotic bone remodelling (otospongiosis). OBJECTIVES: The role of BMPs in various tissue growth and repair mechanisms is an ongoing topic in the literature. BMP-2, -4 and -7 are known to be of major importance in bone formation and repair. Their role in otosclerotic bone transformation has not been analysed previously. The main goal of this study was to perform an immunohistological analysis of BMP-2, -4 and -7 in otoclerosis. MATERIALS AND METHODS: Parts of the stapedial footplates, collected during partial stapedectomies in 30 patients with clinical otosclerosis, were analysed for histological otosclerotic lesions after staining haematoxylin and eosin. Immunohistochemical analysis was performed using polyclonal IgG antibodies for BMP-2, -4 and -7, as well as biotinylated secondary antibodies, avidin-biotin-peroxidase complex reaction and alkaline phosphatase staining. RESULTS: In all, 14 specimens contained otosclerosis; 3 of these were otospongiotic, 8 fibrotic, 2 sclerotic and 1 had both sclerotic and fibrotic lesions. Thus in total 14/30 specimens (47%) showed histological otosclerosis. Only the multiple osteoblasts and osteoclasts in those specimens exhibiting an otospongiotic phase showed distinct immunochemical staining for BMP-2, -4 and -7.     

Bone regeneration in cranial defects previously treated with radiation

OBJECTIVES/HYPOTHESIS: Bone reconstruction in the head and neck region is frequently performed in the context of previous radiation treatment. Thus, the effectiveness of tissue engineering approaches for regenerating bone in radiated defects needs to be determined before considering application to patients. Incomplete healing is described when using osteoinductive protein therapy alone for bone defects previously treated with radiation. We hypothesized that a different approach using ex vivo gene therapy can heal these severely compromised defects. STUDY DESIGN: Animal study using Fisher rats. METHODS: Two weeks before surgery, rats received either no radiation or a 12 Gray radiation dose to the calvarium. Syngeneic dermal fibroblasts were transduced ex vivo using an adenoviral vector containing the cDNA for bone morphogenetic protein (BMP)-7. Critical-sized calvarial defects were created, and either a transduced cell-seeded scaffold or an autologous bone graft was placed into the defect. Nonradiated defects were harvested 4 weeks later for both groups. Radiated defects treated with bone grafts were harvested at 4 weeks, and those treated with gene therapy were harvested either at 4 or 8 weeks. Gross inspection and histology were used to evaluate wound healing. RESULTS: None of the bone grafts had gross or histologic evidence of healing at the wound margins. The nonradiated gene therapy treated defects revealed gross and histologic near-100% bone regeneration by 4 weeks after surgery. By gross inspection, the radiated defects had soft tissue admixed with islands of bone at both 4 and 8 weeks. The histologic appearance revealed areas of dense bone in a nonconfluent pattern admixed with adjacent cells having the morphologic appearance of hypertrophic chondrocytes, suggesting continued endochondral ossification. CONCLUSIONS: Preoperative radiation significantly impairs the ability of BMP-7 ex vivo gene therapy to heal rat critical-sized cranial defects. This finding has significant implications for translating this tissue engineering approach to patients with cancer-related segmental bone defects.     

喉软骨支架缺损应用骨形态发生蛋白再生的实验研究

目的 :观察骨形态发生蛋白 纤维蛋白复合物 (BMP FG)、骨基质明胶 (BMG)、羟基磷灰石 (HA)在行犬甲状软骨缺损移植修复中的效果 ,为寻求一种理想的移植材料提供实验依据。方法 :制备甲状软骨缺损动物模型 ,将其分为 4组 :空白组、HA组、BMG组和BMP FG组 ,分别用相应的上述材料进行修复 ,并于术后 1、2、4、8和12周随机抽取一定数量的犬取材行大体标本观察 ,光镜和电镜检测。结果 :BMP FG和BMG均能诱导缺损部位形成软骨或骨 ,但前者效果明显优于后者 ;HA不能将缺损形成良好修复。结论 :BMP FG是喉软骨缺损修复的良好材料 ,优于BMG ,HA修复效果较差     

耳鼻咽喉科领域的软骨组织工程

耳、鼻、喉和气管的软骨组织工程研究已有较大进展，已分别在裸鼠和具有免疫力动物体内形成了与耳鼻咽喉有关的组织工程化软骨组织，并有初步应用的实验研究报道。随着胚胎干细胞、骨髓基质干细胞、同种异体软骨细胞和智能生物材料的研发和应用，耳鼻咽喉科软骨组织工程有望获得突破性进展。本文综述了该领域的软骨组织工程研究现状和发展趋势。     

Applying an osteoinductive protein complex for regeneration of osseous defects]

INTRODUCTION: Growth factors are still not commercially available for routine clinical use. One possibility might be the application of Colloss, which is supposed to have osteoinductive properties. Therefore, it was the aim of the following animal experimental study to compare Colloss with autogenous bone and to investigate its osteoproductive potential. MATERIAL AND METHODS: In 24 pigs clinically relevant defects were created in the forehead area. Defects were filled with autogenous bone and Colloss. One defect was left unfilled and served as control. After 2, 4, 12 and 26 weeks, six animals were sacrificed and microradiography, light microscopy and immunohistochemistry were carried out using BMP-2 and osteocalcin as antibodies. RESULTS: After 2 weeks the defects filled with the bovine protein complex showed a mineralization of 52.6% +/-4.03 compared to autogenous bone (38% +/-9.9; p=0.068) and the control defect (30% +/-2.94; p=0.05). After 4 weeks the results became assimilated. Light microscopy revealed especially after 2 weeks an enhanced de novo bone formation in the Colloss-group. This was also evident in an early expression maximum of BMP-2 after 2 weeks. Autogenous bone and the control defect showed a later expression maximum. CONCLUSION: Colloss showed an acceleration of bone regeneration in the early phase. Nevertheless, after 26 weeks the results were comparable with the autogenous bone group.     

原位组织工程构建兔听小骨的研究

目的将猪小柱状脱细胞松质骨与骨形态发生蛋白2（bone morphogenetic proteins 2，BMP-2）复合制成听骨赝复物，植入兔听泡内，观察其原位成骨状况。方法制备猪小柱状脱细胞松质骨，与BMP-2复合作为听骨赝复物。选择5只新西兰大耳白兔，采用耳后进路，听泡后外侧骨壁钻孔，清除听泡内部分黏膜组织，一侧植入复合BMP-2听骨赝复物，对侧耳植入单纯脱细胞骨小柱作为对照。术后3个月，通过大体及病理切片观察听骨赝复物成骨情况。结果术后5只兔健康状况良好。术后3个月，植入的复合BMP-2脱细胞松质骨与听泡骨壁接触部位结合紧密，表面被再生黏膜覆盖，病理学检查发现有新骨形成，而对照耳仅有黏膜覆盖，无新骨形成。结论复合BMP-2的猪脱细胞松质骨可于兔听泡内形成新生骨组织，有可能用于听骨链缺损重建。     

下颌骨骨痂组织中TGF-β1及BMP-2的表达及意义

目的：观察转化生长因子β1-（TGF-β1）、骨形成蛋白-2（BMP-2）在人下颌骨骨折骨痂组织中的表达及量的变化。方法：在下颌骨骨折的手术患者中,收集术中去除的骨断端间骨痂组织30例,以2例方颌畸形患者术中切取的下颌角骨块作正常对照;利用SABC免疫组织化学方法检测骨折后不同时期骨痂组织及正常下颌角骨组织中TGF—β、BMP-2的表达。结果：TGF-β1、BMP-2在正常骨组织中没有表达;在不同时期骨痂组织中均有表达,TGF-β1在骨折后第1周到第3周表达量缓慢增加,至第3周时达到高峰,随着时间推移,表达量逐渐下降;BMP-2在骨折后前2周表达呈增加趋势,第2周达到高峰,以后随时间推移,表达量缓慢下降。结论：①BMP-2可能是启动骨折修复的因子之一;②TGF—β1可能是骨折修复的另一条信号通路;③BMP-2与TGF-β1在骨折愈合过程中可能存在协同作用。     

Repair of a rodent nasal critical-size osseous defect with osteoblast augmented collagen gel.

OBJECTIVES/HYPOTHESIS: Facial skeletal defects are a common challenge for the otolaryngologist. Type I collagen gels have shown promise in the repair of nonhealing critical size defects (CSDs) of facial bone by providing scaffolding for new bone growth by osteoblasts at the defect perimeter. The objective of the present study was to evaluate the effect that suspending osteoblasts within a type I collagen gel has on the repair of a rodent facial CSD. STUDY DESIGN: Randomized controlled trial using a rodent model. METHODS: A previously described facial CSD was created by removing the nasalis bones with a cutting burr to the level of the nasal mucosal membranes on 18 Sprague-Dawley rats. Groups of six animals were treated with an implant containing either 300 microg of type I collagen gel, 12 x 10(5) osteoblasts suspended within type I collagen gel, or 12 x 10(5) fibroblasts suspended within type I collagen gel for comparison. After 30 days the animals-were examined at necropsy with planimetry, histological analysis of new bone growth, and radiodensitometric analysis of bone thickness. RESULTS: All animals had complete coverage with a thin layer of bone. Histological sectioning revealed an increased thickness in the osteoblast augmented group. Radiodensitometric measurements revealed a statistically significant increase in bone repair in the osteoblast group compared with the collagen-only group (P < or = .0005) and the fibroblast group (P < or = .04). CONCLUSION: Type I collagen gels augmented with an osteoblastic suspension significantly enhance the repair of nasal CSDs in a rodent model. The use of cultured bone precursor cells represents a leap forward in osteoengineering.     

Mandibular reconstruction with a recombinant bone-inducing factor. Functional, histologic, and biomechanical evaluation

Bone morphogenetic protein-2 (BMP-2) is a human recombinant bone-inducing factor that stimulates bone formation within 14 days. Twenty-six dogs underwent reconstruction of 3-cm full-thickness mandibular defects. After stabilizing the defects with stainless steel reconstruction plates, test implants composed of inactive dog bone matrix carrier and human recombinant BMP-2 were placed in defects of 12 animals (group 1). Control implants (carrier without BMP-2) were used in 10 animals (group 2), and no implants were placed in mandibular defects of four animals (group 3). Animals were killed at 3 and 6 months. The reconstructed segments were evaluated by roentgenography, analysis of functional stability, histology, histomorphometry, and analysis of biomechanical strength using three-point bend testing. In group 1, reconstruction plates were removed at 10 weeks because stiff, noncompressible mineralized bone formed across the defects, allowing the animals to chew a solid diet. The defects from groups 2 and 3 showed minimal, if any, bone formation and remained grossly unstable, prohibiting plate removal or advancement to a solid diet. Histomorphometric analysis at 6 months revealed that 68% of the group 1 implants were replaced by mineralized bone, whereas mineralized bone occupied less than 4% of the implants in groups 2 and 3. Biomechanical testing at 6 months revealed that the average bending strength of the reconstructed hemimandibles (expressed as a percentage of the contralateral hemimandible) was 27% for group 1 and 0% for group 2. The biomechanical strength of the defects reconstructed with BMP-2 increased significantly from 3 to 6 months and was related to degree of mineralization and thickness of bone bridging the defect.     

Comparison of the osteogenic activity of bone morphogenetic protein (BMP) mutants]

BACKGROUND: Modification of the heparin binding site by alteration of the amino acid sequence of bone morphogenetic protein-2 (BMP-2) results in a change in the local retention time. The purpose of this study was to compare the osteogenic activity of T3 and T4, two mutants with increased binding capacity to heparin, and B2GDF-5 a mutant resulting from the fusion of the n-terminal amino acid sequence of BMP-2 and the c-terminal sequence of GDF-5 with wild-type BMP-2 in vivo. MATERIAL AND METHODS: The proteins were coupled to an equine-derived collagen carrier and implanted in standardized critical size calvarial defects in adult rats. After 28 days, bone formation was evaluated radiographically and the new bone was characterized histologically. RESULTS: Proteins T3 and T4 showed a higher osteogenic activity than BMP-2. Less new bone formation was observed with GDF-5 and B2GDF-5 than with-type BMP-2. No difference in bone formation was observed between GDF-5 and B2GDF-5. CONCLUSION: Increased heparin binding capacity enhances osteogenic activity of BMP-2 in vivo. This might be due to a longer retention period in the tissue and thus better bioavailability. Replacement of the N-terminal amino acid sequence of GDF-5 by the corresponding sequence of BMP-2 did not result in an increased osteogenic activity as heparin binding capacity is not the main reason for the bioavailability of GDF-5.     

Concurrent cetuximab and bevacizumab therapy in a murine orthotopic model of anaplastic thyroid carcinoma

OBJECTIVE: To evaluate the therapeutic efficacy of bevacizumab and cetuximab, alone and in combination, in an orthotopic model of anaplastic thyroid carcinoma (ATC) in athymic nude mice. STUDY DESIGN AND SETTING: This was a randomized, controlled in vivo study. MATERIALS AND METHODS: The ATC cell line, ARO, was used to establish orthotopic xenografts of ATC in athymic nude mice. Mice were randomized to therapy for 4 weeks in one of four treatment groups: placebo, cetuximab, bevacizumab, or the combination of cetuximab and bevacizumab. A second study compared the antitumor efficacy of the cetuximab-bevacizumab combination with doxorubicin. In both studies, tumor volumes on completion were measured and compared. Immunohistochemical analysis was performed with antiCD31 and antiproliferating cell nuclear antigen (PCNA) antibodies to assess the in vivo mechanisms of action of these agents. RESULTS: Cetuximab decreased the production of vascular endothelial growth factor by ATC cell lines in vitro. Mean tumor volumes for the control, bevacizumab, cetuximab, and combination groups at the end of the in vivo study were 291, 213, 94, and 42 mm(3), respectively. The differences in mean tumor volume for the control versus treatment groups were statistically significant. Immunohistochemical analysis showed decreased microvessel density and PCNA positivity in the treatment groups. In the doxorubicin comparison study, mean tumor volumes for control, doxorubicin, and combination antibody treatment groups were 175, 162, and 22 mm(3), respectively. CONCLUSIONS: Cetuximab and bevacizumab alone and in combination inhibit tumor growth and angiogenesis in an in vivo model of ATC. Also, this therapy was superior to doxorubicin therapy.     

Linking of bone morphogenetic protein-2 to resorbable fracture plates for enhancing bone healing

OBJECTIVE: To test whether bone morphogenetic protein (BMP)-2 may be covalently linked to resorbable fracture repair plates using an ester-hydrolysis reaction and determining whether the linked compound can facilitate bone growth. STUDY DESIGN: Laboratory in vitro experiments. METHOD: Resorbable fracture repair plates were partially hydrolyzed using varying concentrations of acid or base. This intermediate was then reacted with EDAC (1-ethyl-3[-3-dimethylamino propyl carbodiimide) to form an EDAC intermediate, which was then reacted with either horseradish peroxidase (HRP), interleukin (IL)-2, or BMP-2. Compound binding to the plate was confirmed by immunofluorescent staining. Confirmation of protein function was determined by the following assays: HRP's ability to cleave peroxide, IL-2's ability to stimulate lymphocytes, and BMP-2's ability to stimulate C3H10T1/2 cells to generate alkaline phosphatase. RESULTS: Three compounds (HRP, IL-2, and BMP-2) were successfully linked to plates as confirmed by immunofluorescence staining or functional testing. Compounds demonstrated better covalent linking to plates under basic conditions. HRP, IL-2, and BMP-2 retained function after binding as measured by cleaved peroxide levels, lymphocytes proliferation, and alkaline phosphatase production. CONCLUSIONS: Covalent linking of compounds such as HRP, IL-2, and BMP-2 to resorbable plates is possible and represents a novel protein delivery technique. BMP-2 covalently linked to resorbable plates may be used to facilitate bone healing. Covalent linking of compounds to plates represents a novel method for delivering concentrated levels of growth factors to a specific site and potentially extending their half-life. Further investigation into this application for bone healing may lead to quicker healing.     

Craniofacial and mandibular osseous contour reconstruction: the use of a new "combination" graft.

The use of autogenous bone graft to repair major defects is most feasible biologically. When the bone could not be shaped or carved to fit a given defect, the use of solid alloplastic biomaterial implants gained wide popularity. We are describing a new method wherein a "combination" graft is used. It possesses the advantage of the dependence on autogenous cancellous bone graft, and the added bone inducing capability of a recently developing biomaterial implant (Polyurethane-Terephthalate). The results obtained in the repair of major defects in patients after ablative surgery, or as sequelae of trauma, document the advantages of this new mode of treatment. In selected patients with major defects due to deficiency or absence of the osseous framework of the face, the use of "combination" grafts has proven to be the most appropriate form of repair.     

Repair of nasal defects using collagen gels containing insulin-like growth factor 1

Objective: Facial osseous defects are a common and challenging problem for the otolaryngologist—head and neck surgeon. Current methods of repair including synthetic grafts, cadaveric material, and autologous tissue have drawbacks of foreign body reactions, infectious agent transmission, and the morbidity of a second surgical site. In the effort to develop an ideal technique for osseous reconstruction, a critical-size facial defect has previously been developed in the Sprague-Dawley rat. This model exhibits less than 10% healing by surface area over 6 months. A novel approach to osseous reconstruction is attempted using this model with type I collagen gel augmented with insulin-like growth factor 1 (IGF-1). Study Design: Randomized controlled trial using a rodent model. Methods: Twelve adult male Sprague-Dawley rats underwent a surgical procedure to produce a critical-size nasal defect by removing the nasal bones with a cutting burr. Six animals were repaired with 300 μg of type I collagen gel. Six animals were repaired with 300 μg of type I collagen gel augmented with 3.0 μg of IGF-1. Thirty days later, the animals were examined after necropsy. Precise planimetry, radiodensitometric analysis, and histologic sectioning were performed. Results: All animals had complete coverage of this defect with a thin layer of bone. Radiodensitometric analysis indicated that there was a statistically significant (P < .037) increase in bone density in the collagen plus IGF-1 group compared with that of collagen only. In addition, histologic evaluation revealed increased bone density and thickness in the IGF-1 group. Conclusion: Type I collagen gel augmented with IGF-1 results in a significant increase in healing of a nasal critical-size defect in a rodent model. Laryngoscope, 108:1654–1658, 1998     

Experimental pilot study on surface activation of implants with liposomal vectors]

BACKGROUND: Surface coating with mitogenic or morphogenic proteins can improve the healing of bone adjacent to implants and increase the bone-implant interface. Clinical surveys have shown liposome-mediated gene transfer to be a promising and safe new therapeutic method. The aim of our study was to evaluate an experimental model of new approaches for topical treatment of the implant surface and of periimplant defects by using DNA liposomes encoding for BMP-2 (bone morphogenetic protein). MATERIAL AND METHODS: A total of 27 implants (3.5 x 14 mm) were placed in critically sized defects of the frontal skull bone of adult pigs (n=3). The bottom of the implant was placed in the base of the defect which guaranteed primary stability, whereas the superior part of the implant (10 mm) represented an implant in a defect area. Liposomes containing DNA encoding for BMP-2 and GFP (green fluorescence protein) were used. In a first trial GFP-DNA liposomes on a collagen matrix were directly applied to the periimplant defect. In a second stage, the surface of the implants was encoded with BMP-2 DNA liposomes. Subsequently, these implants were inserted in the manner described. The resulting bone samples were prepared for immunohistochemical staining. Staining for GFP was performed in the area of the defect and for BMP-2 on the bone-implant interface. RESULTS: Immunohistochemical staining on day 3 postoperatively revealed an increased GFP expression in the periimplant defect. Therefore, the effectiveness of the liposomal vector was verified for the chosen animal model. On the surface of the implants encoded with BMP-2 DNA liposomes an increased BMP-2 expression was found. Thus, the liposomal vector system was validated also for BMP-2 DNA transfer in the chosen animal model. Further, the established system allows a sustainable and delayed release of BMP-2 in the area of the bone-implant interface. CONCLUSIONS: As a result of the study we were able to collect data concerning the influence of implant surface conditioning on the bone-implant interface and on therapeutically relevant options for the treatment of periimplant defects. These approaches are currently being evaluated in a long-term study.     

Repair of an osseous facial critical-size defect using augmented fibrin sealant.

OBJECTIVE: Osseous defects of the head and neck are a common challenge for the otolaryngologist. To develop improved reconstructive options, osteoconductive engineering experiments are being conducted. A nasal critical-size defect (CSD) model has previously been described in which less than 7% bone healing is observed over 6 months. An implant containing fibrin sealant with and without osteoprogenitor cells is evaluated in this model. STUDY DESIGN: Randomized controlled trial using a rodent model. METHODS: A nasal CSD was surgically created in 18 male retired breeder Sprague-Dawley rats. Six animals were not implanted with any material, six received fibrin sealant consisting of fibrin (25 mg/mL) and thrombin (1000 U/mL), and six were implanted with fibrin sealant and rat calvarial osteoprogenitor cells (1.8 x 10(6) cells/mL). Thirty days later, the animals were examined at necropsy by planimetry, histological analysis of new bone growth, and radiodensitometric analysis of bone thickness. RESULTS: A thin layer of bone covered the defect in all of the treated animals. A statistically significant increase in bone density (P < .05) between fibrin sealant plus osteoprogenitor cells and each of the other groups was shown using radiodensitometric analysis. Histological analysis also confirmed this difference. CONCLUSION: Osteoprogenitor cells contained within fibrin sealant result in a greater augmentation of bone regeneration than controls or fibrin sealant alone.     

Characteristics of newly-formed cementum following Emdogain application

Periodontal regenerative techniques have been proposed; however, the outcomes remain debatable. The present investigation assessed the regenerated cementum following enamel matrix derivative application in dehiscence-type defects. Buccal osseous dehiscences were surgically created on the maxillary cuspid, and the second and fourth premolars in five female beagle dogs. The treatment group (n=15 sites) received the enamel matrix derived application, whereas the control groups (n=15) did not. The dogs were sacrificed 4 months following treatment and the specimens were histologically and histometrically examined. The newly formed cementum was uneven in thickness and mineralization, overlapped the old cementum and exhibited functional orientation, cementocyte lacunae and collagen fibril bundles. Most of the histological specimens showed the presence of a gap between the newly formed cementum and the underlying dentin. Control sites did not exhibit any cementum formation. The present study concluded that newly formed cementum is of cellular type and exhibits multiple characteristics.     

Pulsed-dye laser and retinoic acid delay progression of oral squamous cell carcinoma: a murine model

OBJECTIVES/HYPOTHESIS: This study examined the role of the pulsed-dye laser (PDL) at 585 nm coupled with retinoic acid at therapeutic (5.0 mg/kg) and nontherapeutic (0.5 mg/kg) doses to delay the progression of cancer with a two-hit approach. The existing vasculature is selectively targeted by the laser, whereas retinoic acid inhibits future angiogenesis. STUDY DESIGN: Randomized, prospective study in a murine model. METHODS: Twenty-five athymic nude mice were inoculated with oral squamous cell cancers on six flank sites and randomly divided into five groups: 1) control subjects, 2) treatment with 0.5 mg/kg retinoic acid (RA 0.5), 3) treatment with 5.0 mg/kg retinoic acid (RA 5.0), 4) treatment with RA 0.5 + PDL, and 5) treatment with RA 5.0 + PDL. The PDL groups received irradiation after inoculation. The retinoic acid was administered daily. The tumors were counted and measured for 14 days. RESULTS: The control group developed visible tumors in 50% of the inoculation sites at 3 days compared with 3 days (RA 0.5) and 4 days (RA 5.0) for the retinoic acid groups and 9 days (RA 0.5 + PDL) and 10 days (RA 5.0 + PDL) for the laser treatment groups. There was no tumor growth until day 7 in the RA 5.0 + PDL group. The tumor volume was statistically different between the treatment groups. CONCLUSION: This study demonstrated the superiority of a single treatment with the PDL coupled with retinoic acid to delay the progression of cancer when compared with treatment with retinoic acid alone, thus introducing a novel strategy in cancer control.