Are Complications Associated With the Repiphysis(®) Expandable Distal Femoral Prosthesis Acceptable for Its Continued Use?

BACKGROUND: Reconstruction of the distal femur after resection for malignant bone tumors in skeletally immature children is challenging. The use of megaprostheses has become increasingly popular in this patient group since the introduction of custom-made, expandable devices that do not require surgery for lengthening, such as the Repiphysis(®) Limb Salvage System. Early reports on the device were positive but more recently, a high complication rate and associated bone loss have been reported. QUESTIONS/PURPOSES: We asked: (1) what are the clinical outcomes using the Musculoskeletal Tumor Society (MSTS) scoring system after 5-year minimum followup in patients treated with this prosthesis at one center; (2) what are the problems and complications associated with the lengthening procedures of this implant; and (3) what are the specific concerns associated with revision of this implant? METHODS: At our institute, between 2002 and 2007, the Repiphysis(®) expandable prosthesis was implanted in 15 children (mean age, 8 years; range, 6-11 years) after distal femoral resection for malignant bone tumors. During this time, the general indication for use of this implant was resection of the distal femur for localized malignant bone tumors in pediatric patients. Alternative techniques used for this indication were modular prosthetic reconstruction, massive (osteoarticular or intercalary) allograft reconstruction, or rotationplasty. Age and tumor extension were the main factors to decide on the surgical indication. Of the 15 patients who had this prosthesis implanted during reconstruction surgery, five died with the implant in situ or underwent amputation before 5 years followup and the remaining 10 were evaluated at a minimum of 5 years (mean, 104 months; range, 78-140 months). No patients were lost to followup. These 10 patients were long-term survivors and underwent the lengthening program. They were included in our study analysis. The first seven lengthening procedures were attempted in an outpatient setting; however, owing to pain and burning sensations experienced by the patients, the procedures failed to achieve the desired lengthening. Therefore, other procedures were performed with the patients under general anesthesia. We reviewed clinical data at index surgery for all 15 patients. We further analyzed the lengthening procedures, implant survival, radiographic and functional results, for the 10 long-term survivors. Functional results were assessed according to the MSTS scoring system. Complications were classified according to the International Society of Limb Salvage (ISOLS) classification system. RESULTS: Nine of the 10 survivors underwent revision of the implant for mechanical failure. They had a mean MSTS score of 64% (range, 47%-87%) before revision surgery. At final followup the 10 long-term surviving patients had an average MSTS score of 81% (range, 53%-97%). In total, we obtained an average lengthening of 39 mm per patient (range, 17-67 mm). Exact expansion of the implant was unpredictable and difficult to control. Nine of 10 of the long-term surviving patients underwent revision surgery of the prosthesis-eight for implant breakage and one for stem loosening. At revision surgery, six patients had another type of expandable prosthesis implanted and three had an adult-type megaprosthesis implanted. In five cases, segmental bone grafts were used during revision surgery to compensate for loss of bone stock. CONCLUSIONS: We could not comfortably expand the Repiphysis(®) prosthesis in an outpatient setting because of pain experienced by the patients during the lengthening procedures. Furthermore, use of the prosthesis was associated with frequent failures related to implant breakage and stem loosening. Revisions of these procedures were complex and difficult. We no longer use this prosthesis and caution others against the use of this particular prosthesis design. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Valves cardiaques par génie tissulaire - Simplification des essais et concept tubulaire

Les substituts valvulaires disponibles actuellement comportent encore plusieurs lacunes. La disponibilité restreinte des allogreffes, les risques de coagulation associés aux valves mécaniques et la durabilité limitée des bioprothèses en tissu animal sont toutes des problématiques que le génie tissulaire a le potentiel de surmonter. Avec la méthode d’auto-assemblage, le seul support des cellules consiste en leur propre matrice extracellulaire, permettant la fabrication d’un tissu entièrement libre de matériau exogène. Ce projet a été précédé par ceux des doctorantes Catherine Tremblay et Véronique Laterreur, ayant respectivement développé une méthode de fabrication de valves moulées par auto-assemblage et une nouvelle version de bioréacteur. Au cours de cette maîtrise, le nouveau bioréacteur a été adapté à une utilisation stérile avec des tissus vivants et la méthode de fabrication de valves moulées a été modifiée puis éprouvée avec la production de 4 prototypes. Ces derniers n’ont pas permis d’obtenir des performances satisfaisantes en bioréacteur, motivant la conception d’une nouvelle méthode. Plutôt que de tenter de répliquer la forme native des valves cardiaques, des études récentes ont suggéré une géométrie tubulaire. Cela permettrait une fabrication simplifiée, une implantation rapide, et un encombrement minimal en vue d’opérations percutanées. Cette approche minimaliste s’accorde bien avec la méthode d’auto-assemblage, qui a déjà été utilisée pour la production de vaisseaux de petits diamètres. Un total de 11 tubes ont été produits par l’enroulement de feuillets fibroblastiques auto-assemblés, puis ont été transférés sur des mandrins de diamètre inférieur, leur permettant de se contracter librement. La caractérisation de deux tubes contrôles a démontré que cette phase de précontraction était bénéfique pour les propriétés du tissu en plus de prévenir la contraction en bioréacteur. Les prototypes finaux pouvaient supporter un écoulement physiologique pulmonaire. Cette nouvelle méthode montre que le procédé d’auto-assemblage a le potentiel d’être utilisé pour fabriquer des valves cardiaques tubulaires.

Human Fetal Progenitor Tenocytes for Regenerative Medicine.

Tendon injuries are very frequent and affect a wide and heterogeneous population. Unfortunately, the healing process is long with outcomes that are not often satisfactory due to fibrotic tissue appearance, which leads to scar and adhesion development. Tissue engineering and cell therapies emerge as interesting alternatives to classical treatments. In this study, we evaluated human fetal progenitor tenocytes (hFPTs) as a potential cell source for treatment of tendon afflictions, as fetal cells are known to promote healing in a scarless regenerative process. hFPTs presented a rapid and stable growth up to passage 9, allowing to create a large cell bank for off-the-shelf availability. hFPTs showed a strong tenogenic phenotype with an excellent stability, even when placed in conditions normally inducing cells to differentiate. The karyotype also indicated a good stability up to passage 12, which is far beyond that necessary for clinical application (passage 6). When placed in coculture, hFPTs had the capacity to stimulate human adult tenocytes (hATs), which are responsible for the deposition of a new extracellular matrix during tendon healing. Finally, it was possible to distribute cells in porous or gel scaffolds with an excellent survival, thus permitting a large variety of applications (from simple injections to grafts acting as filling material). All of these results are encouraging in the development of an off-the-shelf cell source capable of stimulating tendon regeneration for the treatment of tendon injuries.

Mucosite e Peri-Implantite

O processo de infecção no sulco peri-implantar leva, inicialmente, a formação de uma mucosite peri-implantar, que pode ser definida como uma inflamação dos tecidos moles periimplantares, sem ocasionar perda óssea, sendo reversível, se o seu diagnóstico for prematuro. A mucosite é definida como inflamação dos tecidos marginais ao redor dos implantes em função. A doença peri-implantar é caracterizada por um processo inflamatório que ocorre a volta dos implantes osseointegrados em função, afecta tecidos moles e duros, e traz como resultado um quadro de perda do osso de suporte do implante e pode ser diagnosticada da mesma forma que a doença periodontal. O objectivo desse trabalho é fazer uma revisão de literatura específica, entre os anos 2000 e 2015 sobre os aspectos clínicos da mucosite e da doença peri-implantar respectivamente, assim como fatores etiológicos, sinais clínicos e radiográficos da doença, e alguns tratamentos propostos na literatura. Estarão escritos os tratamentos como raspagem e curetagem, tratamentos com produtos químicos, terapia fotodinâmica, antibioticoterapia sistêmica e local, uso de membranas e enxertos ósseos. As doenças peri-implantares podem indicar risco de insucesso para o implante, mas podem também ser temporárias e passíveis de tratamento. O estudo conclui, finalmente, que quanto mais cedo o diagnóstico e intervenção, melhor o resultado do tratamento, sendo essencial o monitoramento pelo médico-dentista dos pacientes implantados.

Regeneração óssea guiada horizontal prévia à colocação de implante

A técnica de Regeneração Óssea Guiada (ROG) é um procedimento que tem por objetivo a reposição do volume ósseo da crista alveolar necessário para garantir o sucesso da reabilitação oral recorrendo a implantes, repondo tanto a componente estética como funcional. Este trabalho foca apenas a ROG horizontal prévia à colocação de implantes e analisa o sucesso e a previsibilidade clínica deste procedimento de aumento ósseo, o sucesso e a sobrevivência de implantes colocados em osso regenerado bem como alguns tipos de enxertos ósseos e membranas. Metodologicamente consiste numa revisão de literatura, baseando-se numa pesquisa de artigos em bases de dados on-line e recorrendo também à consulta de livros em formato digital. As palavras-chave utilizadas na pesquisa on-line foram: “bone healing” AND “tooth extraction”, “bone resoption” AND “tooth extraction”, “bone regeneration” AND “dental implants”, “horizontal guided bone regeneration”, “horizontal guided bone regeneration” AND “dental implants”, “horizontal bone augmentation” “horizontal bone augmentation” AND “dental implants”, “lateral bone augmentation” AND “dental implants”, “horizontal ridge augmentation” AND “dental implants”. A regeneração óssea guiada manifesta comprovado sucesso e previsibilidade no aumento ósseo e os implantes colocados em osso regenerado demonstram sucesso a longo-prazo.

Prevenção da reabsorção óssea alveolar após extração dentária

Introdução: O processo alveolar é o conjunto de osso que se encontra em redor da raiz do dente. Este osso é sensível a uma variedade de fatores ambientais e fisiológicos que influenciam a sua integridade e o seu funcionamento. Como tal, a sua formação assim como a sua preservação é dependente da presença contínua do dente. A reabsorção do processo alveolar após extração dentária é uma consequência natural e fisiológica indesejável, que pode dificultar a colocação de um implante dentário na posição desejada. Com o aumento cada vez mais das demandas estéticas em medicina dentária, torna-se, portanto, necessário prevenir que a reabsorção óssea provoque este defeito na arcada dentária. Objetivos: Realizar uma revisão bibliográfica sobre as várias técnicas e materiais para preservação do rebordo alveolar, a fim de prevenir ou minimizar a reabsorção alveolar após extração dentária. Material e Métodos: A pesquisa foi realizada nas bases de dados Pubmed, B-on e Scielo, não foi aplicado nenhum limite temporal, e os critérios de inclusão foram artigos em língua inglesa e portuguesa. Num total de 164 artigos, selecionaram-se 82 estritamente relacionados com o tema. Os artigos excluídos desviavam-se do objetivo do trabalho ou eram inconclusivos. Selecionaram-se, também, capítulos do livro Clinical Periodontology and Implant Dentistry Volume 1 e 2, dos autores Niklaus P.Lang e Jan Lindhe. Desenvolvimento: De modo a compreender como o processo alveolar reabsorve, deve-se ter em conta as várias técnicas que se podem realizar para permitir uma boa quantidade de osso remanescente na arcada adequada a cada caso para uma possível reabilitação. As técnicas de preservação do osso alveolar após extração passam pela realização de técnicas cirúrgicas minimamente invasivas, estabilização do coágulo pelo princípio da cicatrização por primeira intenção usando membranas ou retalhos, preenchimento do alvéolo dentário com materiais de enxerto ou substitutos ósseos, terapias combinadas com a colocação de implantes imediatos e o recurso a células e fatores de crescimento. Conclusão: A preservação alveolar tem grande importância para uma posterior reabilitação oral com implantes com maior quantidade de osso disponível do que quando não é feita qualquer tipo de preservação. A extração das peças dentárias deve ser feita com cuidado para preservar ao máximo ou não danificar as superfícies ósseas remanescentes. É aconselhado que o encerramento da ferida seja por primeira intenção e que proporcione estabilidade ao coágulo, podendo ser usado retalhos ou mesmo membranas. O uso de enxertos ósseos tem uma importante função de proporcionar uma matriz para o coágulo se formar e promover o processo de cicatrização. O método de implante imediato, para além de ser bastante usado, tem como finalidade o conforto para o paciente de não ser submetido a uma posterior cirurgia para colocação do mesmo e, simultaneamente, mantem a estabilidade dos tecidos moles. Ainda uma técnica menos usada é com células e fatores de crescimento que proporciona uma cicatrização mais rápida e um aumento do potencial regenerativo dos tecidos.

Improving interfaces for nerve repair

Autologous nerve grafts are the current gold standard for the repair of peripheral nerve injuries. However, there is a need to develop an alternative to this technique, as donor-site morbidities such as neuroma formation and permanent loss of function are a few of the limitations concerned with this technique. Artificial nerve conduits have therefore emerged as an alternative for the repair of short peripheral nerve defects of less than 30 mm, however they do not surpass autologous nerve grafts clinically. To develop a nerve conduit that supports regeneration over long nerve gaps and in large diameter nerves, researchers have focused on functionalizing of the conduits by studying the components that enhance nerve regeneration such as micro/nano-topography, growth factor delivery systems, supportive cells and extracellular matrix (ECM) proteins as well as understanding the complex biological reactions that take place during peripheral nerve regeneration. This thesis presents strategies to improve peripheral nerve interfaces to better the regenerative potential by using dorsal root ganglions (DRGs) isolated from neonatal rats as an in vitro model of nerve regeneration. The work started off by investigating the usefulness of a frog foam protein Ranaspumin-2 (Rsn2) to coat biomaterials for compatibility, this lead to the discovery of temporary cell adhesion on polydimethylsiloxane (PDMS), which was investigated as a suitable tool to derive cell-sheets for nerve repair. The influence of Rsn2 anchored to specific adhesion peptide sequences, such as isoleucine-lysine-valine-alanine-valine (IKVAV), a sequence derived from laminin proven to promote cell adhesion and neurite outgrowth, was tested as a useful means to influence nerve regeneration. This approach improves the axonal outgrowth and maintains outgrowth long term. Based on the hypothesis that combinational modulation of substrate topography, stiffness and neurotrophic support, affects axonal outgrowth in whole DRGs, dissociated DRGs were used to assess if these factors similarly act at the single cell level. Rho associated protein kinase (ROCK) and myosin II inhibitors, which affect cytoskeletal contractility, were used to influence growth cone traction forces and have shown that these factors work in combination by interfering with growth cone dynamic creating a different response in axonal outgrowth at the single cell level.

Are Complications Associated With the Repiphysis(®) Expandable Distal Femoral Prosthesis Acceptable for Its Continued Use?

BACKGROUND: Reconstruction of the distal femur after resection for malignant bone tumors in skeletally immature children is challenging. The use of megaprostheses has become increasingly popular in this patient group since the introduction of custom-made, expandable devices that do not require surgery for lengthening, such as the Repiphysis(®) Limb Salvage System. Early reports on the device were positive but more recently, a high complication rate and associated bone loss have been reported. QUESTIONS/PURPOSES: We asked: (1) what are the clinical outcomes using the Musculoskeletal Tumor Society (MSTS) scoring system after 5-year minimum followup in patients treated with this prosthesis at one center; (2) what are the problems and complications associated with the lengthening procedures of this implant; and (3) what are the specific concerns associated with revision of this implant? METHODS: At our institute, between 2002 and 2007, the Repiphysis(®) expandable prosthesis was implanted in 15 children (mean age, 8 years; range, 6-11 years) after distal femoral resection for malignant bone tumors. During this time, the general indication for use of this implant was resection of the distal femur for localized malignant bone tumors in pediatric patients. Alternative techniques used for this indication were modular prosthetic reconstruction, massive (osteoarticular or intercalary) allograft reconstruction, or rotationplasty. Age and tumor extension were the main factors to decide on the surgical indication. Of the 15 patients who had this prosthesis implanted during reconstruction surgery, five died with the implant in situ or underwent amputation before 5 years followup and the remaining 10 were evaluated at a minimum of 5 years (mean, 104 months; range, 78-140 months). No patients were lost to followup. These 10 patients were long-term survivors and underwent the lengthening program. They were included in our study analysis. The first seven lengthening procedures were attempted in an outpatient setting; however, owing to pain and burning sensations experienced by the patients, the procedures failed to achieve the desired lengthening. Therefore, other procedures were performed with the patients under general anesthesia. We reviewed clinical data at index surgery for all 15 patients. We further analyzed the lengthening procedures, implant survival, radiographic and functional results, for the 10 long-term survivors. Functional results were assessed according to the MSTS scoring system. Complications were classified according to the International Society of Limb Salvage (ISOLS) classification system. RESULTS: Nine of the 10 survivors underwent revision of the implant for mechanical failure. They had a mean MSTS score of 64% (range, 47%-87%) before revision surgery. At final followup the 10 long-term surviving patients had an average MSTS score of 81% (range, 53%-97%). In total, we obtained an average lengthening of 39 mm per patient (range, 17-67 mm). Exact expansion of the implant was unpredictable and difficult to control. Nine of 10 of the long-term surviving patients underwent revision surgery of the prosthesis-eight for implant breakage and one for stem loosening. At revision surgery, six patients had another type of expandable prosthesis implanted and three had an adult-type megaprosthesis implanted. In five cases, segmental bone grafts were used during revision surgery to compensate for loss of bone stock. CONCLUSIONS: We could not comfortably expand the Repiphysis(®) prosthesis in an outpatient setting because of pain experienced by the patients during the lengthening procedures. Furthermore, use of the prosthesis was associated with frequent failures related to implant breakage and stem loosening. Revisions of these procedures were complex and difficult. We no longer use this prosthesis and caution others against the use of this particular prosthesis design. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Age-dependence of cultured pearl grade and colour in the black-lipped pearl oyster Pinctada margaritifera

Pinctada margaritifera is an economically important marine bivalve species for cultured pearl production in French Polynesian aquaculture. In order to evaluate the influence of donor oyster age on pearl quality traits, experiments were conducted over 6 years using both grafts and surgreffe operations. At harvest, 6 pearl quality traits were recorded and compared: surface defects, luster, grade, darkness level, and visual color. Analyzing the quality traits of pearls harvested in the initial graft process and those of pearls obtained from surgreffe experiments allowed a comparison of the influence of pearl sac cells originating from the initial mantle graft, which aged together with their recipient oysters. The results demonstrated a significant decrease between these successive grafts in luster, grade (A-B-C,) darkness level, and green color – traits that are of major importance in the pearl market. The duplicated graft experiment allowed the comparison of donor oyster families at 2 and 5 years old, where a mantle graft was inserted into recipient oysters aged 2.5 years old. The results showed the same tendencies to a lesser extent, with 1) an improved pearl grade, predominantly through a most important rate of 0 surface defect category, and 2) a green / grey ratio in favor of the younger donor. A comparison between the graft-surgreffe and the duplicated graft experiments also highlighted: 1) the indirect role played by the younger recipient oysters, which must be optimized for optimal pearl quality realization, and 2) the complex interplay between donor and recipient oysters.

Amélioration des propriétés pharmacocinétiques de peptides par différentes alkylations N-terminales

Modélisations moléculaires réalisés avec le logiciel HyperChem 8.

Adipose-derived stem cell adhesion on laminin-coated microcarriers improves commitment toward the cardiomyogenic lineage

International audience

The Effect of Architecture and Shear Stress on Endothelialization of 3D Printed Vascular Networks

Despite significant progress in the field of tissue engineering within the last decade, a number of unsolved problems still remain. One of the most relevant issues is the lack of proper vascularization that limits the size of engineered tissues to smaller than clinically relevant dimensions. In particular, the growth of engineered tissue in vitro within bioreactors is plagued with this challenge. Specifically, the tubular perfusion system bioreactor has been used for large scale bone constructs; however these engineered constructs lack inherent vasculature and quickly develop a hypoxic core, where no nutrient exchange can occur, thus leading to cell death. Through the use of 3D printed vascular templates in conjunction with a tubular perfusion system bioreactor, we attempt to create an endothelial cell monolayer on 3D scaffolds that could potentially serve as the foundation of inherent vasculature within these engineered bone grafts.

Orthopaedic anaesthesia for upper extremity procedures in a Nigerian hospital

Background General anaesthesia and regional anaesthesia have been used successfully for upper extremity orthopaedic procedures. Despite the advantages of regional anaesthesia, there is low utilisation in Nigeria. In this study, we assessed the types of anaesthesia employed for upper extremity surgeries in our centre. Methods After obtaining approval from the institutional ethics committee, all the patients who had upper extremity surgeries from 1 January 2011 to 31 December 2012 were included in this review. Both prospective and retrospective data were gathered. The choice of anaesthesia was at the discretion of the attending anaesthetist. Results A total of 226 patients with a male-to-female ratio of 1.6:1 and median age of 35.0 (range 2 – 89) years, had orthopaedic upper extremity procedures during the study period. Sixty-three cases (27.9%) had general anaesthesia, 5 (2.2%) combined regional and general anaesthesia while 158 (69.9%) had regional blocks. The regional blocks comprised 145 (89%) different approaches to the brachial plexus and 18 (11%) local anaesthetic infiltrations. The arm was the site mostly operated upon; while supraclavicular and axillary brachial plexus blocks were performed in equal amounts. In 14 (6.2%) patients, brachial plexus blocks were performed with spinal anaesthesia because of concomitant iliac crest bone grafts. While the duration of surgery did not differ significantly, regional anaesthesia provided a significantly longer duration of anaesthesia than general anaesthesia (251 ± 70.8 min versus 141.3 ± 65.5 min; p = 0.0000001). Conclusion There is a high use of regional anaesthesia for upper extremity orthopaedic surgeries in our centre, which is a positive development in a resource limited setting.