Hypoxia-related microRNA-210 is a diagnostic marker for discriminating osteoblastoma and osteosarcoma

MTG6Molecular tumour pathology - and tumour genetic

In vitro and in vivo release of nerve growth factor from biodegradable poly-lactic-co-glycolic-acid microspheres

Regeneration of peripheral nerves after injury is suboptimal. We now report the long term delivery of nerve growth factor (NGF) by biodegradable poly-lactic-co-glycolic acid (PLGA) microspheres in vitro and in vivo. Lactic to glycolic acid ratios of 50:50 and 85:15 were fabricated using the double emulsion solvent, evaporation technique. Three different inherent viscosities (0.1 dL g(-1):1A 0.4 dL g(-1):4A, 0.7 dL g(-1):7A) were analyzed. In vitro, release of NGF for 23 days was measured. Electron microscopy demonstrated intact spheres for at least 7 days (50:50 1A), 14 days (50:50 4A), or 35 days (50:50 7A and 85:15 7A). In vitro release kinetics was characterized by burst release, followed by release of NGF at a rate of 0.6-1.6% a day. Release curves for 50:50 1A and 85:15 7A differed significantly from other compositions (p < 0.01). In vivo, release was characterized by a novel radionuclide tracking assay. Release rates varied from 0.9 to 2.2% per day with linear kinetics. All but the 85:15 type of spheres showed different release profiles in vivo compared to in vitro conditions. On the basis of the surface morphology and release profiles, we found microspheres fabricated from 50:50 4A PLGA to be best suited for the use in a rat sciatic nerve injury model. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 95A: 1067-1073,2010.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Growth factor interactions in bone regeneration

Growth factor interactions in bone regeneration. Diederik H R Kempen, Laura B Creemers, Jacqueline Alblas, Lichun Lu, Abraham J Verbout, Michael J Yaszemski and Wouter J A Dhert 1 Department of Orthopedics, University Medical Center , Utrecht, The Netherlands . AbstractBuy the PDF Pubmed abstract Get permission Buy the PDF Suppl. info HTML version PMID: 21039299 Bone regeneration is a complex process regulated by a large number of bioactive molecules. Many growth factors and cytokines involved in the natural process of bone healing have been identified and tested as potential therapeutic candidates to enhance the regeneration process. Although many of these studies show an enhancement of the bone regeneration process by a single drug therapy, in vivo bone regeneration is the result of a complex interplay between the applied growth factor and various endogenous produced growth factors. To investigate these growth factor interactions, various studies have investigated the effect of growth factor combinations on bone regeneration. This review provides an overview of the growth factor and cytokine combinations tested in translational bone regeneration studies and shows that their interaction may result in an enhancement or inhibition of bone formation

In vitro and in vivo release of nerve growth factor from biodegradable poly-lactic-co-glycolic-acid microspheres

Regeneration of peripheral nerves after injury is suboptimal. We now report the long term delivery of nerve growth factor (NGF) by biodegradable poly-lactic-co-glycolic acid (PLGA) microspheres in vitro and in vivo. Lactic to glycolic acid ratios of 50:50 and 85:15 were fabricated using the double emulsion solvent, evaporation technique. Three different inherent viscosities (0.1 dL g(-1):1A 0.4 dL g(-1):4A, 0.7 dL g(-1):7A) were analyzed. In vitro, release of NGF for 23 days was measured. Electron microscopy demonstrated intact spheres for at least 7 days (50:50 1A), 14 days (50:50 4A), or 35 days (50:50 7A and 85:15 7A). In vitro release kinetics was characterized by burst release, followed by release of NGF at a rate of 0.6-1.6% a day. Release curves for 50:50 1A and 85:15 7A differed significantly from other compositions (p < 0.01). In vivo, release was characterized by a novel radionuclide tracking assay. Release rates varied from 0.9 to 2.2% per day with linear kinetics. All but the 85:15 type of spheres showed different release profiles in vivo compared to in vitro conditions. On the basis of the surface morphology and release profiles, we found microspheres fabricated from 50:50 4A PLGA to be best suited for the use in a rat sciatic nerve injury model. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 95A: 1067-1073,2010

Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit

Single channel conduits are used clinically in nerve repair as an alternative to the autologous nerve graft. Axons regenerating across single channel tubes, however, may disperse resulting in inappropriate target reinnervation. This dispersion may be limited by multichannel nerve conduits as they resemble the structure of nerve multiple basal lamina tubes. In this study, we investigated the influence of channel number on the axonal regeneration using a series of 1-, 2-, 4-, and 7-channel collagen conduits and commercial (NeuraGen (R)) single channel conduits. Nerve conduits were implanted in rats with a 1 cm gap of sciatic nerve. After four months, quantitative results of regeneration were evaluated with nerve morphometry and the accuracy of regeneration was assessed using retrograde tracing: two tracers being applied simultaneously to tibial and peroneal nerves to determine the percentage of motor neurons with double projections. Recovery of function was investigated with compound muscle action potential recordings and ankle motion analysis. We showed that the fabricated 1-channel and 4-channel conduits are superior to other types of conduits in axonal regeneration. Simultaneous tracing showed a significantly lower percentage of motor neurons with double projections after 2- and 4-channel compared with 1-channel conduit repair. This study shows the potential influence of multichannel guidance on limiting dispersion without decreasing quantitative results of regeneration. (C) 2010 Elsevier Ltd. All rights reserved.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Short- and long-term peripheral nerve regeneration using a poly-lactic-co-glycolic-acid scaffold containing nerve growth factor and glial cell line-derived neurotrophic factor releasing microspheres

Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

RAT SCIATIC NERVE REPAIR WITH A POLY-LACTIC-co-GLYCOLIC ACID SCAFFOLD AND NERVE GROWTH FACTOR RELEASING MICROSPHERES

The effect of microsphere delivered Nerve Growth Factor (NGF) in a poly-lactic-co-glycolic-acid (PLGA) 85/15 nerve conduit bridging a 10 mm rat sciatic nerve gap was assessed, comparing nine groups (n = 6): PLGA conduits filled with saline, saline and NGF, saline with blank microspheres; four different NGF microspheres (5, 20, 50, and 100 mg/ml); an autologous graft and sciatic nerve gap. Histomorphometry, retrograde tracing, electrophysiology, and functional outcomes were evaluated up to 16 weeks. The autologous graft showed the largest fascicular area (0.65 mm(2)) and had a significantly greater number of myelinated fibers (P < 0.0001). Electrophysiology showed Compound Muscle Action Potential (CMAP) recordings for the autologous graft returning at 6 weeks after nerve transection, reaching their highest amplitude of 3.6 mV at endpoint. No significant differences were found in functional evaluation between groups or between conduits with microspheres and the saline filled conduit. A PLGA 85/15 nerve conduit is capable of sustaining nerve regeneration. The microsphere delivery system does not interfere with regeneration. (C) 2011 Wiley-Liss, Inc. Microsurgery 31:293-302, 2011.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Estudo da interação polímero/cartilagem/osso utilizando poli (ácido lático-co-ácido glicólico) e poli (p-dioxanona) em condilo femural de coelhos Study of polymer/cartilage/bone interaction using poly(lactic acid-co-glycolic acid) and poly (p-dioxanona) in femoral condyle of rabbits

Os dispositivos biorreabsorvíveis são alternativas para fixação interna das fraturas. Durante o tratamento estes dispositivos mantêm a fixação e degradam-se gradualmente não necessitando de uma cirurgia de remoção, reduzindo o custo de tratamento quando comparadas aos dispositivos metálicos. O objetivo desse trabalho foi estudar a interação polímero/tecido utilizando pinos de PLGA e PDS após implantes em coelhos Nova Zelândia. Separou-se os animais em 3 grupos os quais foram sacrificados após 3, 6 e 12 semanas de implantação e o material obtido foi submetido à análise histológica. As análises histológicas com implantes de PLGA mostraram após 3 semanas a formação de um tecido com características mesenquimatosas e com 12 semanas a formação de uma estrutura óssea madura. Já nos implantes de PDS de 3 semanas houve uma maior invasão de tecido mesenquimal comparado ao PLGA e após 12 semanas, ocorreu uma degradação avançada, com tecido proliferativo mesenquimal e ósseo. Assim, concluiu-se que ocorreram resultados positivos à resposta tecidual/implante e foi relevante a observação da ausência de células responsáveis pela resposta inflamatória. As análises demonstraram que o copolímero de PLGA apresentou propriedades osteoindutivas mais adequadas que os de PDS, apresentando biocompatibilidade aceitável para aplicação ortopédica.<br>Bioresorbable devices are alternatives for internal fixation. During the treatment, those devices maintain the fixation, degrade gradually and eliminate the need for a remove surgery, decreasing the treatment cost when compared with metallic devices. The aim of this work was to study the interaction polymer/tissue interaction using pins of PLGA and PDS implanted in New Zealand rabbits. The animals were separated in 3 groups which were sacrificed after 3, 6 and 12 weeks after implantation, and the obtained material was submitted to histological analysis. Histological analysis with PLGA implants showed after 3 weeks, the growth of a tissue with mesenchimal characteristics, after 3 weeks, with formation of mature bone aready after 12 weeks. PDS implants after 3 weeks showed a bigger invasion of mesenchimal tissue compared to PLGA and after 12 weeks an advanced degradation occurred, with proliferation of mesenchimal and bone tissue formation. It is concluded that the results are highly positive, with the relevant absence of cells responsible for inflammatory response. Analysis showed that the copolymer PLGA has better ostoinductive properties than PDS, showing biocompatibility acceptable for orthopedics application