Human levator veli palatini muscle: a novel source of mesenchymal stromal cells for use in the rehabilitation of patients with congenital craniofacial malformations.

BACKGROUND: Bone reconstruction in congenital craniofacial differences, which affect about 2-3% of newborns, has long been the focus of intensive research in the field of bone tissue engineering. The possibility of using mesenchymal stromal cells in regenerative medicine protocols has opened a new field of investigation aimed at finding optimal sources of multipotent cells that can be isolated via non-invasive procedures. In this study, we analyzed whether levator veli palatini muscle fragments, which can be readily obtained in non-invasive manner during palatoplasty in cleft palate patients, represent a novel source of MSCs with osteogenic potential. METHODS: We obtained levator veli palatini muscle fragments (3-5 mm3), during surgical repair of cleft palate in 5 unrelated patients. Mesenchymal stromal cells were isolated from the muscle using a pre-plating technique and other standard practices. The multipotent nature of the isolated stromal cells was demonstrated via flow cytometry analysis and by induction along osteogenic, adipogenic, and chondrogenic differentiation pathways. To demonstrate the osteogenic potential of these cells in vivo, they were used to reconstruct a critical-sized full-thickness calvarial defect model in immunocompetent rats. RESULTS: Flow cytometry analysis showed that the isolated stromal cells were positive for mesenchymal stem cell antigens (CD29, CD44, CD73, CD90, and CD105) and negative for hematopoietic (CD34 and CD45) or endothelial cell markers (CD31). The cells successfully underwent osteogenic, chondrogenic, and adipogenic cell differentiation under appropriate cell culture conditions. Calvarial defects treated with CellCeram™ scaffolds seeded with the isolated levator veli palatini muscle cells showed greater bone healing compared to defects treated with acellular scaffolds. CONCLUSION: Cells derived from levator veli palatini muscle have phenotypic characteristics similar to other mesenchymal stromal cells, both in vitro and in vivo. Our findings suggest that these cells may have clinical relevance in the surgical rehabilitation of patients with cleft palate and other craniofacial anomalies characterized by significant bone deficit.

Deciduous Dental Pulp Stem Cells for Maxillary Alveolar Reconstruction in Cleft Lip and Palate Patients.

BACKGROUND: To reduce morbidity to cleft patients, new approaches have been developed and here, we report for the first time the use of deciduous dental pulp stem cells (DDPSC) associated with a hydroxyapatite-collagen sponge (Bio-Oss Collagen® 250 mg, Geistlich) for closing alveolar defects during secondary dental eruption, further comparing these results to historical controls. METHODS: Six patients, aged 8 to 12, were selected. Autologous DDPSC were isolated from each patient, then associated with the biomaterial and this bone tissue engineered set was used to fill the alveolar defect. Computed tomography was performed to assess both preoperative and 6- and 12-month postoperative outcomes. Overall morbidity was recorded. Historical controls consisted of sixteen patients previously selected and randomly assigned to group one (rhBMP-2) or group two (iliac crest bone graft). RESULTS: DDPSC could be isolated and characterized as mesenchymal stem cells. Progressive alveolar bone union has occurred in all patients. Similarly to group two 75.4%, SD ± 4.0, p > 0.999, but statistically different from group one (59.6%, SD ± 9.9, p > 0.999, but statistically different from group one (59.6%, SD ± 9.9. CONCLUSION: For this selected group of patients, DDPSC therapy resulted in satisfactory bone healing with excellent feasibility and safety, which adds significantly to the prospect of stem cell use in clinical settings. Clinical Question/Level of Evidence. Therapeutic, II. This trial is registered with https://clinicaltrials.gov/ct2/show/NCT01932164?term=NCT01932164&rank=1.

Facial and Nasolabial Aesthetics of Complete UCLP Submitted to 2-Stage Palate Repair With Vomer Flap.

OBJECTIVE: To evaluate the aesthetics of nasolabial appearance and facial profile of children with unilateral cleft lip and palate (UCLP) submitted to 2-stage palate repair with vomerine flap. DESIGN: Retrospective. SETTING: Single center. PATIENTS: Forty patients with UCLP, mean age of 7.81 years of both sexes, rehabilitated at a single center by 1 plastic surgeon. INTERVENTIONS: Lip and anterior palate repair with nasal alar repositioning was performed at 3 to 6 months of age by Millard technique and vomer flap, respectively. Posterior palate was repaired at 18 months by Von Langenbeck technique. MAIN OUTCOME MEASURE(S): Four cropped digital facial photographs of each patient were evaluated by 3 orthodontists to score the nasolabial aesthetics and profile. Frequencies of each score as well means and medians were calculated. Kappa test was used for evaluating inter- and intrarater reproducibility. RESULTS: The nasal form and deviation was scored as good/very good in 70%, fair in 22.5%, and poor in 7.5% of the sample. The nasal-subnasal aesthetic was considered good/very good in 55%, fair in 30%, and poor in 15% of the sample. The lip vermilion border and the white part of surgical scar aesthetics were good/very good in 77.5% and 80%, fair in 17.5% for both categories, and poor in 5% and 2.5% of the cases, respectively. In all, 67.5% showed convex facial profile, 20% was straight, and 12.5% was concave profile. CONCLUSIONS: Two-stage palatoplasty presented an adequate aesthetical results for the majority of patients with UCLP in the mixed dentition.

Comparative study and histomorphometric analysis of bone allografts lyophilized and sterilized by autoclaving, gamma irradiation and ethylene oxide in rats.

PURPOSE: To compare three sterilization methods (autoclave, gamma irradiation and ethylene oxide) over non demineralized lyophilized bone allografts. METHODS: Bone allografts were implanted on paravertebral muscles of 21 rats. After 30 days animals were sacrificed and grafts underwent comparative analysis regarding histomorphometric and macroscopic parameters. RESULTS: Allografts that underwent the three sterilization methods presents similar weight gain, cortical thickness similar to control group, and less fibrosis than the control group. Grafts that underwent sterilization in autoclave presented less presence of multinucleated giant cells, although not statistically significant. There was also no statistically significant difference regarding mineralization on the three groups. CONCLUSION: The three sterilization methods cause similar effects on bone allografts regarding macroscopic and histomorphometric parameters.

Comparative study and histomorphometric analysis of bone allografts lyophilized and sterilized by autoclaving, gamma irradiation and ethylene oxide in rats

PURPOSE: To compare three sterilization methods (autoclave, gamma irradiation and ethylene oxide) over non demineralized lyophilized bone allografts. METHODS: Bone allografts were implanted on paravertebral muscles of 21 rats. After 30 days animals were sacrificed and grafts underwent comparative analysis regarding histomorphometric and macroscopic parameters. RESULTS: Allografts that underwent the three sterilization methods presents similar weight gain, cortical thickness similar to control group, and less fibrosis than the control group. Grafts that underwent sterilization in autoclave presented less presence of multinucleated giant cells, although not statistically significant. There was also no statistically significant difference regarding mineralization on the three groups. CONCLUSION: The three sterilization methods cause similar effects on bone allografts regarding macroscopic and histomorphometric parameters.

Human bone morphogenetic protein-2 use for maxillary reconstruction in cleft lip and palate patients.

BACKGROUND: The conventional methods of maxillary alveolar reconstruction in patient with cleft are the periosteoplasty and autologous bone grafting. As an important alternative of bone substitution, there is the recombinant human bone morphogenetic protein-2 (rhBMP-2). This study compares the rhBMP-2 with periosteoplasty and autologous bone grafting. METHODS: Patients with cleft and alveolar defect were divided into 3 groups of 6 patients who underwent to autologous iliac crest bone grafting, resorbable collagen sponge with rhBMP2, and periosteoplasty, respectively. The analysis was performed through computed tomographic scan preoperatively and at months 3, 6, and 12 postoperatively. The variables analyzed were the alveolar defect volume, formed bone volume, bone formation rate, maxillary height repair rate, and the formed bone density mean. RESULTS: The formed bone volume was similar comparing the bone graft and BMP groups at 1-year postoperative analysis (P = 0.58). Both of them had the formed bone volume significantly larger than the periosteoplasty group at 3 and 6 months postoperatively. In this last group, the 1-year follow-up was canceled because the bone formation was insufficient. The bone formation rate, the maxillary height repair rate, and the mean of density of the formed bone were similar in the bone graft and BMP groups at 1-year follow-up with P values of 0.93, 0.90, and 0.81, respectively. CONCLUSIONS: The amount of formed bone in the periosteoplasty group was insufficient. There was no difference among the bone graft and rhBMP-2 therapy considering the parameters analyzed.

Evaluation of primary cleft nose repair: severity of the cleft versus final position of the nose.

BACKGROUND: Since 1957, when the concept of rotation-advancement repair was introduced by Millard, this technique has become the procedure of choice for unilateral cleft lip worldwide. More recently, modifications described by Noordhoof, Mohler, Skoog, and McComb started being jointly performed so that better results could be obtained. In this study, the nasal position was evaluated and related to the size of the cleft. The primary unilateral cleft lip repair was performed through a modified technique. METHODS: Forty-five patients with unilateral cleft lip underwent primary surgical repair through this technique. To analyze aesthetic results, a severity classification of deformities and a scoring system for evaluation of the results were established based on nasal alar lateralization, dome position, alignment of bone segments, and deviation of the columella. RESULTS: By means of the established system, 26.6% of mild forms, 13.4% of moderate forms, and 60% of severe forms were observed. Among aesthetic results, 17.8% were found to be good, and 82.2% were considered excellent. Among aspects considered negative, late deformity of the lower lateral cartilage prevailed. CONCLUSIONS: Through the presented evaluation, the authors observed that there was no relation between severity of the cleft and final position of the nose. Among the 27 patients considered to have had severe forms of cleft deformity, 22 were classified as excellent results (81.5%). To obtain better results along time, technical refinements and the critical analysis of results must be performed on a routinely basis.

Modificação na rinoqueiloplastia primária do paciente com fissura labial unilateral / Primary rhinocheiloplasty modification for unilateral cleft lip patients

Introdução: Desde 1957, quando Millard introduziu o conceito de reparo tipo avanço e rotação, este se tornou o procedimento de escolha para o reparo da fissura labial unilateral em todo o mundo. Mais recentemente, modificações descritas por Noordhoof, Mohler, Skoog e McComb passaram a ser realizadas em associação para que melhores resultados pudessem ser obtidos. Neste trabalho, os resultados estéticos e o padrão de crescimento ósseo facial do reparo primário da fissura labial unilateral através de técnica modificada são sistematicamente apresentados. Método: Quarenta e cinco pacientes portadores de fissura labial unilateral foram submetidos ao reparo cirúrgico primário por meio da técnica proposta. Para a análise dos resultados, foi estabelecido um sistema de pontuação dos resultados estéticos e a avaliação do padrão de crescimento ósseo facial foi realizada com emprego do índicede Atack. Resultados: Verificamos que 17,8% dos pacientes apresentaram bons resultados estéticos e 82,2%, resultados considerados excelentes. Entre os aspectos considerados negativos, houve predomínio da deformidade tardia da cartilagem lateral inferior (37,8%). Quanto ao índice de Atack, 83,4% dos pacientes apresentaram índice 1 e 16,6% índice 2 de Atack. Conclusões: Por meio da abordagem para rinoqueiloplastia primária apresentada, independentemente do tipo de fenda, é possível a obtenção de bons resultados estéticos e funcionais. Para que melhores resultados possam ser obtidos ao longo do tempo, refinamentos técnicos e a análise criteriosa dos resultados devem ser rotineiramente buscados.

Introduction: Since 1957, when Millard introduced the concept of rotation-advancement repair, this technique has become the procedure of choice for unilateral cleft lip worldwide. More recently, modifications described by Noordhoof, Mohler, Skoog, and McComb started being jointly performed so that better results could be obtained. In this study, the aesthetic results and the facial growth pattern after primary unilateral cleft lip repair through a modified technique are presented. Methods: Forty-five patients with unilateral cleft lip underwent primary surgical repair through this technique. For results analysis, a scoring system for aesthetic results was established and to evaluate the facial bone growth pattern the Atack’ Index was used. Results: By means of the established technique, 17.8% presented good aesthetic results and 82.2% were considered excellent results. Among aspects considered negative, late deformity of the lower lateral cartilage prevailed (37.8%). We observed that 83.4% had Atack’ Index 1 and 16.6% had Atack’ Index 2. Conclusions: Through the presented primary rhinocheiloplasty approach, regardless of cleft type, it is possible to obtain good aesthetic and functional results. In order to obtain better results along time, technical refinements and the criterial analysis of results must be performed on a routinely basis.

Evaluation of maxillary alveolar reconstruction using a resorbable collagen sponge with recombinant human bone morphogenetic protein-2 in cleft lip and palate patients.

INTRODUCTION: A resorbable collagen matrix with recombinant human bone morphogenetic protein (rhBMP-2) was compared with traditional iliac crest bone graft for the closure of alveolar defects during secondary dental eruption. METHODS: Sixteen patients with unilateral cleft lip and palate, aged 8 to 12 years, were selected and randomly assigned to group 1 (rhBMP-2) or group 2 (iliac crest bone graft). Computed tomography was performed to assess both groups preoperatively and at months 6 and 12 postoperatively. Bone height and defect volume were calculated through Osirix Dicom Viewer (Pixmeo, Apple Inc.). Overall morbidity was recorded. RESULTS: Preoperative and follow-up examinations revealed progressive alveolar bone union in all patients. For group 1, final completion of the defect with a 65.0% mean bone height was detected 12 months postoperatively. For group 2, final completion of the defect with an 83.8% mean bone height was detected 6 months postoperatively. Dental eruption routinely occurred in both groups. Clinical complications included significant swelling in three group 1 patients (37.5%) and significant donor-site pain in seven group 2 patients (87.5%). CONCLUSIONS: For this select group of patients with immature skeleton, rhBMP-2 therapy resulted in satisfactory bone healing and reduced morbidity compared with traditional iliac crest bone grafting.

Fissuras labiopalatinas: protocolo de atendimento multidisciplinar e seguimento longitudinal em 91 pacientes consecutivos / Cleft lip and palate: protocol of multidisciplinary team treatment and longitudinal

Introdução: A fissura labiopalatina é a malformação congênita mais frequente da face. É imperativaa necessidade dos pacientes fissurados serem avaliados e acompanhados em centrosde referência por equipe multidisciplinar. Atualmente, não há consenso na literatura quanto aomelhor protocolo de tratamento a ser seguido, estudos comparativos entre a escolha do tipode técnica, momento ideal para as intervenções cirúrgicas e para o apoio multidisciplinar sãoamplamente realizados. Objetivo: Este estudo tem por objetivo apresentar o protocolo utilizadopor centro de referência multidisciplinar nacional, demonstrando sua experiência anual.Método: Estudo prospectivo, no qual 91 pacientes portadores de fissura labiopalatina foramoperados no período de 12 meses, submetidos a tratamento mediante protocolo pré-determinadoe analisados de acordo com a localização da deformidade, características morfológicase tipo de procedimento realizado. Resultados: Oito categorias cirúrgicas foram relatadas;palatoplastia (41,58%) foi a mais realizada, seguida por queiloplastia (unilateral e bilateral),sendo 90% primária. A técnica descrita por Von Langenbeck associada a veloplastia intravelarestendida foi realizada em 97,5% dos casos. Todos os casos de queiloplastia unilateral foramsubmetidos a uma variante da técnica de Millard 2. Realizou-se enxerto ósseo alveolar secundárioem 70% dos casos. Faringoplastia foi realizada em dois pacientes e em 15 casos foramnecessários procedimentos de revisão de lábio e nariz. Conclusão: Análises periódicas dosdados obtidos devem ser realizadas, com objetivo de obter em longo prazo consensos quantoao melhor planejamento terapêutico do paciente portador de fissura labiopalatina.

Introduction: The cleft lip and palate is the most frequent congenital malformation of theface. It’s imperative that cleft lip and palate patients be evaluated and seen in centers ofreference by multidisciplinary teams. At present, there’s no consensus in the literature asto the best treatment protocol to be followed, although comparative studies on the choicesof technique types, the ideal moment for the surgical interventions and the multidisciplinarysupport are broadly carried out. Objectives: Present the protocol utilized by nationalmultidisciplinary reference center, showing its annual experience. Methods: Prospectivestudy, 91 patients with cleft lip and palate were operated in 12 months period, submittedto treatment following pre-determined protocol and analyzed according to location of thedeformity, morphologic characteristics and kind of procedure carried out. Results: Eightsurgical categories were related, palate repair (41.58%) was the most utilized one followedby lip repair (unilateral and bilateral), 90% of it primary. The technique described by VonLangenbeck associated to the extended intravelar veloplasty was carried out in 97.5% of thecases. The technique of unilateral cleft lip repair was variant of the Millard 2 procedure. In83.5% of the bilateral ones, the Spina technique was carried out and in the remainder, thevariant one of the Millard 2 technique was chosen. Secondary alveolar bone graft was performedin 70% of the cases. Conclusion: Periodic analyses of the data obtained must be done;to achieve, tire long term consensus as for the best therapeutic planning of these patients.

Fraturas de face: analise de 130 de casos / Facial fractures: analysis of 130 cases

A violencia dos grandes centros urbanos tem contribuido em muito para manter a elevada incidencia de fraturas de face. Sao casos que devem ser tratados adequadamente para evitar sequelas esteticas e funcionais e poder reintegrar os pacientes a sociedade. A partir de 1990, com a organizacao de equipe de Cirurgia Plastica no Pronto-Socorro do Hospital das Clinicas da Faculdade de Medicina de Sao Paulo, as fraturas de face vem sendo tratadas por elas. Em levantamento dos pacientes atendidos consecutivamente em 28 meses, analisamos os agentes etiologicos envolvidos e a frequencia dos diversos tipos de trauma. Em 130 casos analisados, o principal agente etiologico foi o acidente automobilistico (51 por cento) e a fratura mais encontrada foi a de mandibula (46 por cento). Uma correlacao entre o tipo trauma e o tipo de fratura foi realizada.

Classificaçäo das fissuras lábio-palatais: breve histórico, consideraçöes clínicas e sugestäo de modificaçäo / Classification of cleft lip and palate: brief review, clinical considerations and suggestion of modification

Após descrita a classificaçäo de Spina e cols. e exemplificada a apresentaçäo de casos clínicos, é apresentada uma proposta de modificaçäo, que consiste em acrescentar no grupo II (fissura transforame incisivo) a fissura mediana, tornando assim a presente classificaçäo mais completa, como esquematizado a seguir: Grupo II - fissura transforame incisivo: unilateral (lado esquerdo/lado direito); bilateral; mediana

Tratamento cirúrgico da craniostenose da sutura metópica / Surgical treatment of craniostenosis of the metopic suture

Os autores propöem a correçäo da craniostenose simples da sutura metópica mediante craniotomia osteoplástica frontoparietotemporal e craniectomia subtemporal, feitas bilateralmente, com o avanço do andar anterior da capacidade volumétrica das órbitas. Asim tratadas, oito crianças evoluíram de maneira excelente, tanto no aspecto comético como funcional, sem a necessidade de novas intervençöes cirúrgicas