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2.
Cell Tissue Res ; 366(1): 101-11, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27083447

RESUMO

Bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-ß (TGF-ß) super-family, is one of the main chondrogenic growth factors involved in cartilage regeneration. BMP2 is known to induce chondrogenic differentiation in various types of stem cells in vitro. However, BMP2 also induces osteogenic differentiation and endochondral ossification in mesenchymal stem cells (MSCs). Although information regarding BMP2-induced chondrogenic and osteogenic differentiation within the same system might be essential for cartilage tissue engineering, few studies concerning these issues have been conducted. In this study, BMP2 was identified as a regulator of chondrogenic differentiation, osteogenic differentiation and endochondral bone formation within the same system. BMP2 was used to regulate chondrogenic and osteogenic differentiation in stem cells within the same culture system in vitro and in vivo. Any changes in the differentiation markers were assessed. BMP2 was found to induce chondrogenesis and osteogenesis in vitro via the expression of Sox9, Runx2 and its downstream markers. According to the results of the subcutaneous stem cell implantation studies, BMP2 not only induced cartilage formation but also promoted endochondral ossification during ectopic bone/cartilage formation. In fetal limb cultures, BMP2 promoted chondrocyte hypertrophy and endochondral ossification. Our data reveal that BMP2 can spontaneously induce chondrogenic differentiation, osteogenic differentiation and endochondral bone formation within the same system. Thus, BMP2 can be used in cartilage tissue engineering to regulate cartilage formation but has to be properly regulated for cartilage tissue engineering in order to retain the cartilage phenotype.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular , Condrogênese , Osteogênese , Células-Tronco/citologia , Células-Tronco/metabolismo , Adenoviridae/metabolismo , Animais , Biomarcadores/metabolismo , Desenvolvimento Ósseo , Condrócitos/patologia , Colágeno/metabolismo , Extremidades/embriologia , Feto/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Hipertrofia , Camundongos , Coloração e Rotulagem
3.
Cell Physiol Biochem ; 36(1): 44-60, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25924688

RESUMO

BACKGROUND/AIMS: Joint cartilage defects are difficult to treat due to the limited self-repair capacities of cartilage. Cartilage tissue engineering based on stem cells and gene enhancement is a potential alternative for cartilage repair. Bone morphogenetic protein 2 (BMP2) has been shown to induce chondrogenic differentiation in mesenchymal stem cells (MSCs); however, maintaining the phenotypes of MSCs during cartilage repair since differentiation occurs along the endochondral ossification pathway. In this study, hypoxia inducible factor, or (HIF)-1α, was determined to be a regulator of BMP2-induced chondrogenic differentiation, osteogenic differentiation, and endochondral bone formation. METHODS: BMP2 was used to induce chondrogenic and osteogenic differentiation in stem cells and fetal limb development. After HIF-1α was added to the inducing system, any changes in the differentiation markers were assessed. RESULTS: HIF-1α was found to potentiate BMP2-induced Sox9 and the expression of chondrogenesis by downstream markers, and inhibit Runx2 and the expression of osteogenesis by downstream markers in vitro. In subcutaneous stem cell implantation studies, HIF-1α was shown to potentiate BMP2-induced cartilage formation and inhibit endochondral ossification during ectopic bone/cartilage formation. In the fetal limb culture, HIF-1α and BMP2 synergistically promoted the expansion of the proliferating chondrocyte zone and inhibited chondrocyte hypertrophy and endochondral ossification. CONCLUSION: The results of this study indicated that, when combined with BMP2, HIF-1α induced MSC differentiation could become a new method of maintaining cartilage phenotypes during cartilage tissue engineering.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Condrogênese , Membro Anterior/crescimento & desenvolvimento , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células-Tronco Mesenquimais/fisiologia , Osteogênese , Animais , Proteína Morfogenética Óssea 2/genética , Diferenciação Celular , Células Cultivadas , Membro Anterior/embriologia , Regulação da Expressão Gênica , Células HEK293 , Humanos , Cartilagem Hialina/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Camundongos , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo
4.
Nanomedicine (Lond) ; 9(1): 77-87, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23799985

RESUMO

AIM: We developed biodegradable, lidocaine-embedded poly([D,L]-lactide-co-glycolide) nanofibers for epidural analgesia to reduce the severe pain in rats after laminectomies. MATERIALS & METHODS: Nanofibers were prepared by an electrospinning process and were introduced into the epidural space of rats after laminectomy. The lidocaine concentration, postoperative bodyweight change and amount of food/water intake were monitored to evaluate the analgesic effectiveness of the drug-eluting nanofibers. RESULTS: It was demonstrated that the nanofibers provided a sustained release of lidocaine for more than 2 weeks, and the local pharmaceutical concentration was much higher than the concentration in plasma. Rats that received laminectomies without nanofibers exhibited the greatest bodyweight reduction. The food/water intake and activity performance were significantly higher in rats receiving laminectomies with nanofibers than in rats without nanofibers. CONCLUSION: The results of this study suggest that the lidocaine-loaded nanofibers can provide an easy, practical and safe means of achieving effective postlaminectomy analgesia.


Assuntos
Plásticos Biodegradáveis/química , Sistemas de Liberação de Medicamentos , Lidocaína/administração & dosagem , Nanofibras/administração & dosagem , Animais , Dioxanos/administração & dosagem , Dioxanos/química , Espaço Epidural , Humanos , Laminectomia , Lidocaína/química , Nanofibras/química , Ratos
5.
ACS Chem Neurosci ; 4(9): 1314-21, 2013 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-23815098

RESUMO

Successful treatment of a brain infection requires aspiration of the pus or excision of the abscess, followed by long-term (usually 4-8 weeks) parenteral antibiotic treatment. Local antibiotic delivery using biodegradable drug-impregnated carriers is effective in treating postoperative infections, thereby reducing the toxicity associated with parenteral antibiotic treatment and the expense involved with long-term hospitalization. We have developed vancomycin-loaded, biodegradable poly[lactic-co-glycol acid] nanofibrous membranes for the sustainable delivery of vancomycin to the brain tissue of rats by using the electrospinning technique. A high-performance liquid chromatography assay was employed to characterize the in vitro and in vivo release behaviors of pharmaceuticals from the membranes. The experimental results suggested that the biodegradable nanofibers can release high concentrations of vancomycin for more than 8 weeks in the cerebral cavity of rats. Furthermore, the membranes can cover the wall of the cavity after the removal of abscess more completely and achieve better drug delivery without inducing adverse mass effects in the brain. Histological examination also showed no inflammation reaction of the brain tissues. By adopting the biodegradable, nanofibrous drug-eluting membranes, we will be able to achieve long-term deliveries of various antibiotics in the cerebral cavity to enhance the therapeutic efficacy of cerebral infections.


Assuntos
Implantes Absorvíveis , Antibacterianos/administração & dosagem , Abscesso Encefálico/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Ácido Láctico , Membranas Artificiais , Nanofibras , Ácido Poliglicólico , Vancomicina/administração & dosagem , Absorção , Animais , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Encéfalo/ultraestrutura , Cromatografia Líquida de Alta Pressão , Terapia Combinada , Portadores de Fármacos , Avaliação Pré-Clínica de Medicamentos , Implantes de Medicamento , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade , Distribuição Aleatória , Ratos , Vancomicina/efeitos adversos , Vancomicina/uso terapêutico , Cicatrização
6.
Expert Opin Drug Deliv ; 10(7): 879-88, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23289446

RESUMO

OBJECTIVE: Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans. The only interstitial chemotherapy pharmaceutical approved to date for GBM treatment is the Gliadel® wafer. Despite the safety and efficacy of this approach that have been demonstrated in patients undergoing resection of both newly diagnosed and recurrent malignant gliomas, the wafer provides an effective release of the anticancer 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for only 5 days. METHODS: In this study, the authors developed biodegradable poly[(d,l)-lactide-co-glycolide] nanofibrous membranes via electrospinning that provided a sustained release of BCNU. An elution method and a HPLC assay were employed to characterize the in vitro and in vivo release behaviors of pharmaceuticals from the electrospun membranes. RESULTS: The experimental results show that the biodegradable, nanofibrous membranes released high concentrations of BCNU for more than 6 weeks in the cerebral cavity of rats. Furthermore, the membranes can better conform to the geometry of the brain tissue and can cover more completely the tissue after the removal of tumors, achieving better drug transport without interfering with the normal function of the brain. Histological examination showed no obvious inflammation reactions of the brain tissues. CONCLUSION: Adopting the electrospinning technique will help in manufacturing biodegradable, nanofibrous membranes for the long-term deliveries of various anticancer drugs in the cerebral cavity, which will further enhance the therapeutic efficacy of GBM treatment.


Assuntos
Antineoplásicos Alquilantes/farmacocinética , Materiais Biocompatíveis/química , Carmustina/farmacocinética , Córtex Cerebral/metabolismo , Portadores de Fármacos/química , Implantes de Medicamento , Ácido Láctico/química , Ácido Poliglicólico/química , Implantes Absorvíveis , Animais , Antineoplásicos Alquilantes/administração & dosagem , Disponibilidade Biológica , Transporte Biológico , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Carmustina/administração & dosagem , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Nanofibras , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Wistar
7.
Antimicrob Agents Chemother ; 57(1): 9-14, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22948881

RESUMO

Guided tissue regeneration (GTR) therapy has been widely used to regenerate lost periodontium from periodontal disease. However, in terms of regenerative periodontal therapy, a multidrug-loaded biodegradable carrier can be even more promising in dealing with periodontal disease. In the current study, we fabricated biodegradable nanofibrous collagen membranes that were loaded with amoxicillin, metronidazole, and lidocaine by an electrospinning technique. The in vitro release behavior and the cytotoxicity of the membranes were investigated. A four-wall intrabony defect was created in rabbits for in vivo release analysis. The bioactivity of the released antibiotics was also examined. The experimental results showed that the drug-loaded collagen membranes could provide sustainable release of effective amoxicillin, metronidazole, and lidocaine for 28, 56, and 8 days, respectively, in vivo. Furthermore, the bioactivity of the released antibiotics remained high, with average bioactivities of 50.5% for amoxicillin against Staphylococcus aureus and 58.6% for metronidazole against Escherichia coli. The biodegradable nanofibrous multipharmaceutical membranes developed in this study may provide a promising solution for regenerative periodontal therapy.


Assuntos
Amoxicilina/farmacocinética , Antibacterianos/farmacocinética , Materiais Biocompatíveis/química , Preparações de Ação Retardada/química , Regeneração Tecidual Guiada/métodos , Lidocaína/farmacocinética , Metronidazol/farmacocinética , Amoxicilina/farmacologia , Animais , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Biópsia por Agulha Fina , Sobrevivência Celular/efeitos dos fármacos , Colágeno/química , Preparações de Ação Retardada/farmacologia , Avaliação Pré-Clínica de Medicamentos , Técnicas Eletroquímicas , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Lidocaína/farmacologia , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Coelhos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Tíbia/efeitos dos fármacos , Tíbia/cirurgia
8.
Int J Pharm ; 430(1-2): 335-41, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22521880

RESUMO

This study investigated the in vitro release of vancomycin, gentamicin, and lidocaine from novel electrospun sandwich-structured polylactide-polyglycolide (PLGA)/collagen nanofibrous membranes. For the electrospinning of biodegradable membranes, PLGA/collagen and PLGA/vancomycin/gentamicin/lidocaine were separately dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). They were then electrospun into sandwich structured membranes, with PLGA/collagen for the surface layers and PLGA/drugs for the core layer. After electrospinning, an elution method and HPLC assay were employed to characterize the in vitro release rates of the pharmaceutics over a 30-day period. The experiment showed that biodegradable nanofibrous membranes released high concentrations of vancomycin and gentamicin (well above the minimum inhibition concentration) for 4 and 3 weeks, respectively, and lidocaine for 2 weeks. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity of vancomycin and gentamicin ranged from 30% to 100% and 37% to 100%, respectively. In addition, results indicated that the nanofibrous membranes were functionally active in responses in human fibroblasts. By adopting the electrospinning technique, we will be able to manufacture biodegradable biomimetic nanofibrous extracellular membranes for long-term drug delivery of various pharmaceuticals.


Assuntos
Anestésicos Locais/química , Antibacterianos/química , Colágeno/química , Portadores de Fármacos , Gentamicinas/química , Ácido Láctico/química , Lidocaína/química , Membranas Artificiais , Nanofibras , Ácido Poliglicólico/química , Vancomicina/química , Anestésicos Locais/administração & dosagem , Antibacterianos/administração & dosagem , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Química Farmacêutica , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Colágeno/toxicidade , Preparações de Ação Retardada , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Composição de Medicamentos , Estabilidade de Medicamentos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Fibroblastos/efeitos dos fármacos , Gentamicinas/administração & dosagem , Humanos , Lactente , Cinética , Ácido Láctico/toxicidade , Lidocaína/administração & dosagem , Testes de Sensibilidade Microbiana , Nanotecnologia , Ácido Poliglicólico/toxicidade , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Propanóis/química , Solubilidade , Solventes/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Tecnologia Farmacêutica/métodos , Vancomicina/administração & dosagem
9.
Int J Nanomedicine ; 7: 763-71, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22359454

RESUMO

BACKGROUND: The purpose of this study was to develop novel sandwich-structured nanofibrous membranes to provide sustained-release delivery of vancomycin, gentamicin, and lidocaine for repair of infected wounds. METHODS: To prepare the biodegradable membranes, poly(D, L)-lactide-co-glycolide (PLGA), collagen, and various pharmaceuticals, including vancomycin, gentamicin, and lidocaine, were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into sandwich-structured membranes with PLGA/collagen as the surface layers and PLGA/drugs as the core. An elution method and a high-pressure liquid chromatography assay were used to characterize in vivo and in vitro drug release from the membranes. In addition, repair of infected wounds in rats was studied. Histological examination of epithelialization and granulation at the wound site was also performed. RESULTS: The biodegradable nanofibrous membranes released large amounts of vancomycin and gentamicin (well above the minimum inhibition concentration) and lidocaine in vivo for more than 3 weeks. A bacterial inhibition test was carried out to determine the relative activity of the antibiotics released. The bioactivity ranged from 40% to 100%. The nanofibrous membranes were functionally active in treating infected wounds, and were very effective as accelerators in early-stage wound healing. CONCLUSION: Using the electrospinning technique, we will be able to manufacture biodegradable, biomimetic, nanofibrous, extracellular membranes for long-term delivery of various drugs.


Assuntos
Bandagens , Preparações de Ação Retardada/farmacologia , Membranas Artificiais , Nanofibras/química , Cicatrização/efeitos dos fármacos , Análise de Variância , Animais , Lesões nas Costas/tratamento farmacológico , Lesões nas Costas/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Técnicas Eletroquímicas , Gentamicinas/química , Gentamicinas/farmacocinética , Gentamicinas/farmacologia , Histocitoquímica , Lidocaína/química , Lidocaína/farmacocinética , Lidocaína/farmacologia , Ratos , Ratos Sprague-Dawley , Vancomicina/química , Vancomicina/farmacocinética , Vancomicina/farmacologia , Cicatrização/fisiologia
10.
Anim Reprod Sci ; 123(3-4): 221-33, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21183296

RESUMO

The development of the testes includes changes in cell morphology and endocrine levels that are essential for the maturation of males. A large number of novel proteins are expressed throughout testis development and play important roles in spermatogenesis. Differences in protein expressions during the development of porcine testes have not been systematically studied. The purpose of this study was to investigate differential protein expression in porcine testes during postnatal development. Testes from four pigs each at 1wk, 3mo, and 1yr of age were used for a proteomic analysis. Expression levels of 264 protein spots were quantified using the Melanie 3 software. In total, 108 protein spots showed more than 2-fold differences (P<0.05) among developmental stages, and 90 of them were successfully identified by mass spectrometry. The proteins were sorted based on whether the expression levels increased with age (36.1%), decreased with age (38.0%), or fluctuated among different developmental stages (25.9%). In total, 69 unique gene products were further classified according to their gene ontology annotations. A majority of the proteins are organelle proteins (41%) with the nucleus and mitochondria being the main organelles. About 45% of the proteins have a protein binding domain and are likely involved in protein-protein interactions. Finally, a large proportion of these differentially expressed proteins are involved in cellular (25%) and metabolic (22%) processes. Identifying these differentially expressed proteins should be valuable for exploring developmental biology and the pathology of male reproduction.


Assuntos
Proteínas/análise , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/metabolismo , Testículo/química , Testículo/metabolismo , Animais , Animais Recém-Nascidos , Análise por Conglomerados , Eletroforese em Gel Bidimensional , Imuno-Histoquímica , Masculino , Espectrometria de Massas , Metaboloma , Proteínas/metabolismo , Proteoma/análise , Proteoma/metabolismo , Análise de Sequência de Proteína , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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