Adel Alhadlaq

Tissue-engineered Neogenesis of Human-shaped Mandibular Condyle from Rat Mesenchymal Stem Cells

The temporomandibular joint is susceptible to diseases and trauma that may ultimately lead to structural degeneration. Current approaches for replacing degenerated mandibular condyles suffer from deficiencies such as donor site morbidity, immunorejection, implant wear and tear, and pathogen transmission. The hypothesis of this study was that a human-shaped mandibular condyle can be tissue-engineered from rat mesenchymal stem cells (MSCs) encapsulated in a biocompatible polymer. Rat bone marrow MSCs were isolated and induced to differentiate into chondrogenic and osteogenic cells in vitro, and encapsulated in poly(ethylene glycol)-based hydrogel in two stratified layers molded into the shape of a cadaver human mandibular condyle. Eight weeks following in vivo implantation of the bilayered osteochondral constructs in the dorsum of immunodeficient mice, mandibular condyles formed de novo. Microscopic evaluation of the tissue-engineered mandibular condyle demonstrated two stratified layers of histogenesis of cartilaginous and osseous phenotypes. The current approach is being refined for ultimate therapeutic applications.

Adult stem cell driven genesis of human-shaped articular condyle.

Uniform design of synovial articulations across mammalian species is challenged by their common susceptibility to joint degeneration. The present study was designed to investigate the possibility of creating human-shaped articular condyles by rat bone marrow-derived mesenchymal stem cells (MSCs) encapsulated in a biocompatible poly(ethylene glycol)-based hydrogel. Rat MSCs were harvested, expanded in culture, and treated with either chondrogenic or osteogenic supplements. Rat MSC-derived chondrogenic and osteogenic cells were loaded in hydrogel suspensions in two stratified and yet integrated hydrogel layers that were sequentially photopolymerized in a human condylar mold. Harvested articular condyles from 4-week in vivo implantation demonstrated stratified layers of chondrogenesis and osteogenesis. Parallel in vitro experiments using goat and rat MSCs corroborated in vivo data by demonstrating the expression of chondrogenic and osteogenic markers by biochemical and mRNA analyses. Ex vivo incubated goat MSC-derived chondral constructs contained cartilage-related glycosaminoglycans and collagen. By contrast, goat MSC-derived osteogenic constructs expressed alkaline phosphatase and osteonectin genes, and showed escalating calcium content over time. Rat MSC-derived osteogenic constructs were stiffer than rat MSC-derived chondrogenic constructs upon nanoindentation with atomic force microscopy. These findings may serve as a primitive proof of concept for ultimate tissue-engineered replacement of degenerated articular condyles via a single population of adult mesenchymal stem cells.

Tissue-engineered osteochondral constructs in the shape of an articular condyle

BACKGROUND An entire articular condyle engineered from stem cells may provide an alternative therapeutic approach to total joint replacement. This study describes our continuing effort to optimize the chondrogenic and osteogenic differentiation from mesenchymal stem cells toward engineering articular condyles in vivo. METHODS Primary rat bone-marrow mesenchymal stem cells were induced to differentiate into chondrogenic and osteogenic lineages in vitro and were suspended in polyethylene glycol-based hydrogel. The hydrogel cell suspensions, each at a density of 20 x 10(6) cells/mL, were stratified into two separate layers that were molded into the shape and dimensions of an adult human cadaveric mandibular condyle by sequential photopolymerization. The osteochondral constructs fabricated in vitro were implanted in the dorsum of immunodeficient mice for twelve weeks. RESULTS De novo formation of articular condyles in the shape and dimensions of the adult human mandibular condyle occurred after a twelve-week period of in vivo implantation. Histological evaluation demonstrated two stratified layers of cartilaginous and osseous tissues, and yet there was mutual infiltration of cartilage-like and bone-like tissues into each others territories. The cartilaginous portion was stained intensively to safranin O and expressed immunolocalized type-II collagen. Chondrocytes adjacent to the tissue-engineered osteochondral junction were enlarged and expressed type-X collagen, typical of hypertrophic chondrocytes. The osseous portion contained bone trabeculae-like structures and expressed immunolocalized type-I collagen, osteopontin, and osteonectin. CONCLUSIONS A cell encapsulation density of 20 million cells/mL with in vivo incubation for twelve weeks yields further tissue maturation and phenotypic growth of both cartilage-like and bone-like tissues in the tissue-engineered articular condyle.

Effect of Therapeutic Ultrasound on Human Periodontal Ligament Cells for Dental and Periodontal Tissue Engineering

The objective of this study was to investigate whether low intensity pulsed ultrasound (LIPUS) has anabolic effects on human periodontal ligament (PDL) cells. The PDL cells were plated in 48-well plates and cultured at 37°C in an atmosphere of 5% CO2 in air, in a humidified incubator until confluent. The cells were divided into three groups including control, 5 min and 10 min ultrasound application. The LIPUS was applied using a 2.5 transducer that produces an incident intensity of 30 mW/cm2 of the transducers surface area. The results from the quantitative polymerase chain reaction (PCR) indicates that expression levels of alkaline phosphatase (ALP),cyclin D1 (CYC), nucleostemin (NCT) were increased after four weeks of 10 minutes of daily ultrasound treatment. The increased ALP/DNA by LIPUS shows a time dependent pattern with the highest activity occurring after four weeks of treatment. These results demonstrate that LIPUS has an anabolic effect on PDL cells and suggest that LIPUS may enhance the pluripotent characteristics of PDL cells as indicated by the up-regulation of NCT, a stem marker. These results also may explain the potential role of LIPUS in periodontal tissue regeneration.

Controlled release of injectable liposomal in situ gel loaded with recombinant human bone morphogenetic protein-2 for the repair of alveolar bone clefts in rabbits

Abstract Background and objective: The aim of the present study was to develop and examine a new non-invasive injectable graft for the repair of alveolar bone clefts using recombinant human bone morphogenetic protein-2 (rhBMP-2) encapsulated within injectable liposomal in situ gel (LIG). Method: Different liposomal formulations loaded with rhBMP-2 were prepared, and the effects of the preparation methods and lipid content on the efficiency of rhBMP-2 encapsulation within the liposomes were studied. For the preparation of in situ gel, deacetylated gellan gum (DGG) was used, and the in vitro gelation characteristics of the gel were evaluated. In vivo pharmacokinetics and histology were also assessed. Critical size alveolar defects were surgically created in the maxillae of 30 New Zealand rabbits and treated with different injectable formulae, including rhBMP-2 liposomes and in situ gel (rhBMP-2-LIG). Results: The results indicated that the prepared rhBMP-2-LIG prolonged the release and residence time of BMP-2 within rabbits for more than 7 days. Histomorphometric assessment showed 67% trabecular bone filling of the defects treated using this novel formula. Conclusion: BMP-2-LIG is a promising delivery device for the repair of alveolar bone defects associated with cleft deformities.

Rapid maxillary expansion effects in Class II malocclusion: A systematic review

OBJECTIVE To evaluate the effectiveness of rapid maxillary expansion (RME) on the sagittal dental or skeletal parameters of growing children with Class II malocclusion. MATERIALS AND METHODS A systematic review intended to identify relevant literature was conducted. The search was performed on Medline, Embase, Cochrane Library, and Scopus databases. Reference lists of the included articles were also screened for relevant documents. The qualitative assessment was performed according to the Methodological Index for Non-Randomized Studies (MINORS) tool, and the resultant data were grouped and analyzed concerning dental and skeletal sagittal effects of RME. RESULTS Of 25 screened studies, seven articles met eligibility criteria and were included. Study samples were observed during mixed dentition stage and characterized as having either Class II dental malocclusion or skeletal discrepancy. None of the included studies was a randomized clinical trial. Included controlled studies presented several inadequacies related to control group or lacked appropriate comparative statistical analysis. Besides being frequently based on deficient methodology, dental and skeletal sagittal effects of RME were either controversial or lacked clinical relevance. CONCLUSION The effect of RME on the sagittal dimension of Class II malocclusions has not been proved yet. Future randomized controlled clinical trials are still needed to definitely address this question.

New Therapeutics in Promoting and Modulating Mandibular Growth in Cases with Mandibular Hypoplasia

Children with mandibular growth deficiency may develop airway obstruction. The standard treatment of severe airway obstruction involves invasive procedures such as tracheostomy. Mandibular distraction osteogenesis has been proposed in neonates with mandibular deficiency as a treatment option to avoid tracheostomy procedure later in life. Both tracheostomy and distraction osteogenesis procedures suffer from substantial shortcomings including scarring, unpredictability, and surgical complications. Forward jaw positioning appliances have been also used to enhance mandible growth. However, the effectiveness of these appliances is limited and lacks predictability. Current and future approaches to enhance mandibular growth, both experimental and clinical trials, and their effectiveness are presented and discussed.

Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation

Objective The aim of this study is to utilize the biocompatibility characteristics of biodegradable polymers, viz, poly lactide-co-glycolide (PLGA) and polycaprolactone (PCL), to prepare sustained-release injectable nanoparticles (NPs) of bone morphogenetic protein-2 (BMP-2) for the repair of alveolar bone defects in rabbits. The influence of formulation parameters on the functional characteristics of the prepared NPs was studied to develop a new noninvasive injectable recombinant human BMP-2 (rhBMP-2) containing grafting material for the repair of alveolar bone clefts. Materials and methods BMP-2 NPs were prepared using a water-in-oil-in-water double-emulsion solvent evaporation/extraction method. The influence of molar ratio of PLGA to PCL on a suitable particle size, encapsulation efficiency, and sustained drug release was studied. Critical size alveolar defects were created in the maxilla of 24 New Zealand rabbits divided into three groups, one of them treated with 5 μg/kg of rhBMP-2 NP formulations. Results The results found that NPs formula prepared using blend of PLGA and PCL in 4:2 (w/w) ratio showed the best sustained-release pattern with lower initial burst, and showed up to 62.7% yield, 64.5% encapsulation efficiency, 127 nm size, and more than 90% in vitro release. So, this formula was selected for scanning electron microscope examination and in vivo evaluation. Histomorphometric analysis showed 78% trabecular bone fill, mostly mature bone in the defects treated with rhBMP-2 in NPs within 6 weeks. Conclusion The prepared NPs prolonged the release and the residence time of rhBMP-2 in rabbits, which led to the formation of adequate bone in critical size alveolar bone defects in 6 weeks. This noninvasive method has application for the primary restoration of alveolar bone defects.

Anchorage condition during canine retraction using transpalatal arch with continuous and segmented arch mechanics

OBJECTIVE To compare anchorage condition in cases in which transpalatal arch was used to enhance anchorage in both continuous and segmented arch techniques. MATERIALS AND METHODS Twenty cases that required first premolar extraction for orthodontic treatment and transpalatal arch to enhance anchorage were included in this study. Ten cases were treated using the continuous arch technique, while the other 10 cases were treated using 0.019 × 0.025-inch TMA T-loops with posterior anchorage bend according to the Burstone and Marcotte description. Lateral cephalometric analysis of before and after canine retraction was performed using Ricketts analysis to measure the anteroposterior position of the upper first molar to the vertical line from the Pt point. Data were analyzed using an independent sample t-test. RESULTS There was a statistically significant forward movement of the upper first molar in cases treated by continuous arch mechanics (4.5 ± 3.0 mm) compared with segmented arch mechanics (-0.7 ± 1.4 mm; P  =  .01). CONCLUSIONS The posterior anchorage bend to T-loop used to retract the maxillary canine can enhance anchorage during maxillary canine retraction.

Adjunctive techniques for enhancing mandibular growth in Class II malocclusion

Class II malocclusions are generally characterized by mandible retrusion. For this reason, forward bite jumping appliances, also known as functional appliances were originally designed to enhance mandibular forward projection. However, there is still insufficient evidence to support the effectiveness, predictability and stability of functional appliances in modifying mandibular growth. This article was aimed at presenting evidences and hypotheses that mandibular growth may be enhanced through the use of adjunctive methods in conjunction with functional appliances. In formulating our hypothesis, we considered relevant data, mostly derived from animal studies, concerning alternative methods, such as low-intensity ultrasound and light-emitting diode, as well as their related cellular and molecular mechanisms. According to the evidences covered in this article, we suggest that both methods are potentially effective, and theoretically able to act in synergistic way to enhance functional appliances treatment on mandibular and condylar additional growth. The rationale for the use of these methods as adjunctive therapies for mandibular underdevelopment is attributed to their abilities on stimulating angiogenesis, cell differentiation, proliferation, and hypertrophy, as well as enhancing matrix production and endochondoral bone formation, especially on the condyle of growing animals. This article also proposed a study design which would be able to either prove or refute our hypothesis. If ratified, it would represent a significant scientific accomplishment which provides support for further investigations to be carried out on well-designed clinical trials.