RESUMO
The incidence of atypical femoral fractures (AFFs) was 2.95% among 6644 hip and femoral fractures. Independent risk factors included the use of bisphosphonates (BPs), osteopenia or osteoporosis, rheumatoid arthritis, increased femoral curvatures, and thicker femoral cortices. Patients with AFFs and BP treatment were more likely to have problematic healing than those with typical femoral fractures (TFFs) and no BP treatment. INTRODUCTION: To determine the incidence and risk factors of atypical femoral fractures (AFFs), we performed a multicenter case-control study. We also investigated the effects of bisphosphonates (BPs) on AFF healing. METHODS: We retrospectively reviewed the medical records and radiographs of 6644 hip and femoral fractures of patients from eight tertiary referral hospitals. All the radiographs were reviewed to distinguish AFFs from TFFs. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and interaction analyses were used to investigate the effects of BPs on fracture healing. RESULTS: The incidence of AFFs among 6644 hip and femoral fractures was 2.95% (90 subtrochanter and 106 femoral shaft fractures). All patients were females with a mean age of 72 years, and 75.5% were exposed to BPs for an average duration of 5.2 years (range, 1-17 years). The use of BPs was significantly associated with AFFs (p < 0.001, odds ratio = 25.65; 95% confidence interval = 10.74-61.28). Other independent risk factors for AFFs included osteopenia or osteoporosis, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex at the shaft level. Interaction analyses showed that patients with AFFs using BPs had a significantly higher risk of problematic fracture healing than those with TFFs and no BP treatment. CONCLUSIONS: The incidence of AFFs among 6644 hip and femoral fractures was 2.95%. Osteopenia or osteoporosis, use of BPs, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex were independent risk factors for the development of AFFs. Patients with AFFs and BP treatment were more likely to have problematic fracture healing than those with TFFs and no BP treatment.
Assuntos
Fraturas do Fêmur/epidemiologia , Consolidação da Fratura , Fraturas Espontâneas/epidemiologia , Fraturas do Quadril/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/farmacologia , Estudos de Casos e Controles , Difosfonatos/efeitos adversos , Difosfonatos/farmacologia , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/fisiopatologia , Consolidação da Fratura/efeitos dos fármacos , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/fisiopatologia , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/etiologia , Fraturas do Quadril/fisiopatologia , Humanos , Incidência , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Radiografia , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
Polymorphisms near the interleukin (IL) 28B gene have been proposed to be associated with spontaneous clearance of the hepatitis C virus. The purpose of this study was to assess the relationship between IL28B polymorphisms and the rate of spontaneous hepatitis B surface antigen (HBsAg) seroclearance by means of meta-analysis. MEDLINE/PubMed and EMBASE were utilized to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were analysed together to assess the strength of the association. Subgroup analyses were mainly performed according to ethnicity. A total of 4028 cases with persistent chronic hepatitis B and 2327 spontaneously recovered controls were included from 11 studies. The single nucleotide polymorphism (SNP), rs12979860, had no significant association with HBsAg seroclearance (OR = 0.98, 95% CI: 0.84-1.14 in the dominant model; OR = 1.00, 95% CI: 0.68-1.46 in the recessive model; and OR = 0.95, 95% CI: 0.82-1.09 in the allelic model). The SNP, rs12980275, had no significant association either (OR = 1.03, 95% CI: 0.84-1.26 in the dominant model; OR = 1.17, 95% CI: 0.46-2.96 in the recessive model; and OR = 1.04, 95% CI: 0.86-1.26 in the allelic model), nor did the SNP, rs8099917 (OR = 0.94, 95% CI: 0.77-1.15 in the dominant model; OR = 0.74, 95% CI: 0.34-1.62 in the recessive model; and OR = 0.93, 95% CI: 0.77-1.13 in the allelic model). Similarly, the results of subgroup analyses by ethnicity also showed no association in either the Asian group or non-Asian group. We concluded that there was no significant association between common IL28B polymorphisms and the rate of spontaneous HBsAg seroclearance.
Assuntos
Antígenos de Superfície da Hepatite B/imunologia , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Interleucinas/genética , Polimorfismo Genético , Humanos , Interferons , Razão de Chances , Viés de PublicaçãoRESUMO
SUMMARY: We evaluated trends in the incidences of typical and atypical hip fracture in relation to bisphosphonate use in Korea from 2006 to 2010, using nationwide data obtained from the Health Insurance Review and Assessment Service (HIRA). INTRODUCTION: Recently, atypical hip fractures in the subtrochanteric region have been reported among patients on bisphosphonate. However, the association between atypical hip fracture and bisphosphonate is controversial. We evaluated trends in the incidences of typical and atypical hip fracture in relation to bisphosphonate use in Korea from 2006 to 2010, using nationwide data obtained from the HIRA. METHODS: All new visits or admissions to clinics or hospitals for a typical and atypical hip fractures were recorded nationwide by HIRA using the ICD-10 code classification. Typical and atypical hip fractures were defined as femoral neck/intertrochanteric and subtrochanteric fracture, respectively. Bisphosphonate prescription data were also abstracted from the HIRA database. RESULTS: The absolute number of typical and atypical hip fracture increased during the study period. Although age-adjusted incidence rates of typical hip fractures were stable in men and women, those of atypical hip fractures increased in women. Nationally, the annual numbers of prescriptions of bisphosphonate also increased during the study period. CONCLUSIONS: The results of this study suggest a possible causal relationship between bisphosphonate use and the increased incidence of atypical hip fracture in Korea.
Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Fraturas do Quadril/induzido quimicamente , Idoso , Bases de Dados Factuais , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/tendências , Feminino , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologiaRESUMO
OBJECTIVES: High salt intake results in various harmful effects on human health including hypertension, cardiovascular disease, and reduced bone density. Despite this, there are very few studies in the literature that have investigated the association between sodium intake and osteoarthritis (OA). Therefore, we aimed to explore these associations in a Korean population. METHODS: This study used cross-sectional data from adult subjects aged 50-75 years from two consecutive periods of the Korean National Health and Nutrition Examination Survey V-VII (2010-2011 and 2014-2016). The estimated 24-hour urinary sodium excretion (24HUNa) was used as a surrogate marker of salt intake. In the 2010-2011 dataset, knee OA (KOA) was defined as the presence of the radiographic features of OA and knee pain. The association between KOA and salt intake was analysed using univariable and multivariable logistic regression methods. For the sensitivity analysis, the same procedures were conducted on subjects with self-reported OA (SR-OA) with knee pain in the 2010-2011 dataset and any site SR-OA in the 2014-2016 dataset. RESULTS: Subjects with KOA had significantly lower energy intake, but higher 24HUNa than those without KOA. The restricted cubic spline plots demonstrated a J-shaped distribution between 24HUNa and prevalent KOA. When 24HUNa was stratified into five groups (<2, 2-3, 3-4, 4-5 and ≥5 g/day), subjects with high sodium intake (≥5 g/day) had a higher risk of KOA (odds ratio [OR] = 1.64, 95% confidence interval [CI] 1.03-2.62) compared to the reference group (3-4 g/day) after adjusting for covariates. The sensitivity analysis based on SR-OA with knee pain showed that high sodium intake was also significantly associated with increased prevalence of OA (OR = 1.84, 95% CI 1.10-3.10) compared with the reference group. Regarding SR-OA at any site in the 2014-2016 dataset, estimated 24HUNa showed a significantly positive association with the presence of SR-OA after adjusting for potential confounders. CONCLUSIONS: This nationwide Korean representative study showed a significant association between symptomatic KOA and high sodium intake (≥5 g/day). Avoidance of a diet high in salt might be beneficial as a non-pharmacologic therapy for OA.
Assuntos
Osteoartrite do Joelho , Estudos Transversais , Humanos , Inquéritos Nutricionais , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/etiologia , Dor/etiologia , Sódio , Cloreto de Sódio na DietaRESUMO
The majority of reports concern external snapping hips caused by the iliotibial band. Comparatively, little information is available regarding snapping hips caused by a gluteus maximus. Here we show that hip problems caused by a tight gluteus maximus can be treated using a modified Z-plasty technique. Fourteen hips in seven patients were diagnosed as snapping hips caused by a tight gluteus maximus. The main functional impairment is that when the hips were flexed, legs were abducted widely and could not be adducted. All had functional impairments irresponsive to conservative treatments besides snapping, whether painful or not, and all patients underwent surgery using a modified Z-plasty technique on the iliotibial band. All patients were followed up and the mean follow-up was 7 years. All patients had complete resolution of functional impairments, snapping, and pain after surgery. No patient needed revision surgery, and there were no complications, such as, abductor weakness, or irritation over the greater trochanter. We suggest that the intrinsic tendon contracture can cause serious functional impairment in patients with snapping due to a tight gluteus maximus. In this context, a modified Z-plasty technique offers a good surgical approach.
Assuntos
Nádegas/cirurgia , Articulação do Quadril/cirurgia , Músculo Esquelético/cirurgia , Adulto , Feminino , Humanos , Masculino , Amplitude de Movimento Articular/fisiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Biofabrication aims to fabricate biologically functional products through bioprinting or bioassembly (Groll et al 2016 Biofabrication 8 013001). In biofabrication processes, cells are positioned at defined coordinates in three-dimensional space using automated and computer controlled techniques (Moroni et al 2018 Trends Biotechnol. 36 384-402), usually with the aid of biomaterials that are either (i) directly processed with the cells as suspensions/dispersions, (ii) deposited simultaneously in a separate printing process, or (iii) used as a transient support material. Materials that are suited for biofabrication are often referred to as bioinks and have become an important area of research within the field. In view of this special issue on bioinks, we aim herein to briefly summarize the historic evolution of this term within the field of biofabrication. Furthermore, we propose a simple but general definition of bioinks, and clarify its distinction from biomaterial inks.
Assuntos
Materiais Biocompatíveis/análise , Bioimpressão/instrumentação , Impressão Tridimensional/instrumentação , Animais , Humanos , TintaRESUMO
The epidermal growth factor receptor (HER1) has been implicated in regenerative growth and proliferative diseases of the human bladder epithelium (urothelium), however a cognate HER1 ligand that can act as a growth factor for normal human urothelial cells (HUC) has not been identified. Here we show that heparin-binding EGF-like growth factor (HB-EGF), an activating HER1 ligand, is an autocrine regulator of HUC growth. This conclusion is based on demonstration of HB-EGF synthesis and secretion by primary culture HUC, identification of HER1 as an activatable HB-EGF receptor on HUC surfaces, stimulation of HUC clonal growth by HB-EGF, inhibition of HB-EGF-stimulated growth by heparin and of log-phase growth by CRM 197, a specific inhibitor of HB-EGF/HER1 interaction, and identification of human urothelium as a site of HB-EGF precursor (proHB-EGF) synthesis in vivo. ProHB-EGF expression was also detected in the vascular and detrusor smooth muscle of the human bladder. These data suggest a physiologic role for HB-EGF in the regulation of urothelial proliferation and regeneration subsequent to mucosal injury. Expression of proHB-EGF is also a feature of differentiated vascular and detrusor smooth muscle in the bladder. Because proHB-EGF is known to be the high affinity diphtheria toxin (DT) receptor in human cells, synthesis of the HB-EGF precursor by human urothelium also suggests the possibility of using the DT-binding sites of proHB-EGF as an in vivo target for the intraluminal treatment of urothelial diseases.
Assuntos
Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Epidérmico/fisiologia , Músculo Liso/metabolismo , Bexiga Urinária/crescimento & desenvolvimento , Bexiga Urinária/metabolismo , Urotélio/crescimento & desenvolvimento , Urotélio/metabolismo , Proteínas de Bactérias/farmacologia , Northern Blotting , Western Blotting , Células Cultivadas , Criança , Pré-Escolar , Cromatografia de Afinidade , Cromatografia Líquida de Alta Pressão , Células Clonais/metabolismo , Sondas de DNA , Toxina Diftérica/farmacologia , Fator de Crescimento Epidérmico/imunologia , Fator de Crescimento Epidérmico/uso terapêutico , Receptores ErbB/metabolismo , Receptores ErbB/fisiologia , Heparina/metabolismo , Heparina/farmacologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Músculo Liso/citologia , Ésteres de Forbol/farmacologia , Fosforilação , RNA/análise , RNA/metabolismo , Tirosina/metabolismo , Doenças da Bexiga Urinária/tratamento farmacológico , Urotélio/citologiaRESUMO
Penile conditions, such as Peyronie's disease or tumor resection may require surgical reconstruction of the tunica albuginea. Various materials have been proposed, as a biomaterial for tunica albuginea repair, however, little functional data are available. We examined the applicability and functional outcome of a collagen-based matrix derived from the bladder (acellular bladder matrix (ABM)), as a biomaterial for tunica repair. Biocompatibility testing was performed on the matrix, which included mitochondrial metabolic activity, cell viability and apoptosis. Approximately 50% of the dorsal penile tunica albuginea was replaced with the collagen-based matrix patch after surgical removal in 24 New Zealand White rabbits. Cavernosometry and cavernosography were performed. The animals were killed 1, 2 and 3 months after surgery for analyses. The matrix showed excellent biocompatibility. All animals implanted with the matrix survived without any noticeable untoward effects. There was no evidence of inflammation or infection at the time of retrieval. Cavernosometry of the implanted animals demonstrated normal intracavernosal pressures with visual erections. Cavernosography of the repaired corpora showed a normal anatomical configuration. Biomechanical analysis of the retrieved matrices demonstrated similar tensile strengths as native tunica. Histologically, there was only a minimal inflammatory response, which gradually decreased over time. These results show that ABM is biocompatible, durable and effective when used as a tunica substitute. The matrix may be useful as an off-the-shelf biomaterial for patients requiring tunica albuginea repair.
Assuntos
Matriz Extracelular/metabolismo , Bexiga Urinária/metabolismo , Animais , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Fenômenos Biomecânicos , Células Cultivadas , Masculino , Teste de Materiais , Microscopia Eletrônica de Varredura , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Pênis/fisiologia , Pênis/cirurgia , Coelhos , SuínosRESUMO
Human organ replacement is limited by a donor shortage, problems with tissue compatibility, and rejection. Creation of an organ with autologous tissue would be advantageous. In this study, transplantable urinary bladder neo-organs were reproducibly created in vitro from urothelial and smooth muscle cells grown in culture from canine native bladder biopsies and seeded onto preformed bladder-shaped polymers. The native bladders were subsequently excised from canine donors and replaced with the tissue-engineered neo-organs. In functional evaluations for up to 11 months, the bladder neo-organs demonstrated a normal capacity to retain urine, normal elastic properties, and histologic architecture. This study demonstrates, for the first time, that successful reconstitution of an autonomous hollow organ is possible using tissue-engineering methods.
Assuntos
Bexiga Urinária/transplante , Coletores de Urina , Animais , Cães , Imuno-Histoquímica , Músculo Liso/citologia , Músculo Liso/metabolismo , Músculo Liso/transplante , Radiografia , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/fisiologia , Urotélio/citologia , Urotélio/metabolismo , Urotélio/transplanteRESUMO
BACKGROUND: Rifaximin might decrease the risk of portal hypertension-related complications by controlling small intestinal bacterial overgrowth. AIM: To evaluate whether rifaximin was associated with the risk of death and cirrhotic complications. METHODS: We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non-HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding. RESULTS: In the non-HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio [aHR], 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile-associated diarrhoea was not different between the groups (aHR, 0.028; P = .338). CONCLUSIONS: In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy.
Assuntos
Anti-Infecciosos/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Rifamicinas/uso terapêutico , Idoso , Infecções Bacterianas/prevenção & controle , Carcinoma Hepatocelular/tratamento farmacológico , Varizes Esofágicas e Gástricas/prevenção & controle , Feminino , Encefalopatia Hepática/complicações , Humanos , Lactulose/uso terapêutico , Cirrose Hepática/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Peritonite/prevenção & controle , Recidiva , Estudos Retrospectivos , Rifaximina , Prevenção SecundáriaRESUMO
Premature loss of provisional scaffold formation has been identified as one of the factors responsible for poor healing of intraarticular tissues. To address this deficiency, substitute provisional scaffolds are being developed. The function of these scaffolds can be enhanced by the addition of specific extracellular matrix proteins. In this study, it was hypothesized that the addition of thrombin to a provisional scaffold material would result in increases in cell proliferation, collagen production, and cell migration within the scaffold. These three parameters are thought to be critical components of wound healing. Gels containing fibrin and collagen supplemented with either 0, 10.5, 21, or 42 U/mL of thrombin were placed in contact with explants of tissue from the anterior cruciate ligament. The addition of thrombin stimulated cell migration at low concentrations and impaired migration at higher concentrations, and had no significant effect on cell proliferation or collagen production. The use of all concentrations of thrombin resulted in mechanically weaker gels. Thus, the use of thrombin to optimize a collagen-platelet rich plasma (PRP) provisional scaffold must be done with caution, and use of high concentrations of thrombin (>42 IU/mL) should be avoided specifically in situations where gel strength or cell ingrowth is important. Use of low concentrations of thrombin (10.5 IU/mL) may be beneficial in applications where a faster set time and enhanced cell migration are desirable and the gel mechanical strength is of secondary importance.
Assuntos
Ligamento Cruzado Anterior/efeitos dos fármacos , Colágeno/metabolismo , Fibroblastos/efeitos dos fármacos , Hemostáticos/farmacologia , Hidrogéis/metabolismo , Trombina/farmacologia , Animais , Ligamento Cruzado Anterior/citologia , Ligamento Cruzado Anterior/fisiologia , Bovinos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/citologia , Fibroblastos/fisiologia , Joelho de Quadrúpedes , Cicatrização/efeitos dos fármacosRESUMO
OBJECTIVES: The search for a suitable material to reconstruct the genitourinary tract has been a challenging task. Bowel has been widely used for urinary tract reconstruction, despite its subsequent complications. We investigated the possibility of using allogenic bladder submucosa, a tissue consisting of nonimmunogenic acellular collagen, either with or without cells, as a material for bladder augmentation. METHODS: Partial cystectomies were performed in 10 beagle dogs. Both urothelial and smooth muscle cells were harvested and expanded separately in 5 animals. The allogenic bladder submucosa obtained from sacrificed dogs was seeded with muscle cells on one side and urothelial cells on the opposite side. All beagles underwent cruciate cystotomies on the bladder dome. Augmentation cystoplasty was performed with the allogenic bladder submucosa seeded with cells in 5 animals and with the allogenic bladder submucosa without cells in 5. The augmented bladders were retrieved 2 and 3 months after augmentation. RESULTS: Bladders augmented with the allogenic bladder submucosa seeded with cells showed a 99% increase in capacity compared with bladders augmented with the cell-free allogenic bladder submucosa, which showed only a 30% increase in capacity. All dogs showed a normal bladder compliance, as evidenced by urodynamic studies. Histologically, all retrieved bladders contained a normal cellular organization consisting of a urothelial lined lumen surrounded by submucosal tissue and smooth muscle. Immunocytochemical analyses confirmed the urothelial and muscle cell phenotype and showed the presence of nerve fibers. CONCLUSIONS: These results show that allogenic bladder submucosa seeded with cells appears to be an excellent option as a biomaterial for bladder augmentation.
Assuntos
Transplante de Células , Bexiga Urinária/citologia , Bexiga Urinária/cirurgia , Animais , Cães , Estudos de ViabilidadeRESUMO
The concept of cell transplantation using tissue engineering techniques has provided numerous possibilities in the area of urologic tissue reconstruction. Tissue engineering applications in the genitourinary tract system have been investigated in almost every tissue in order to improve, restore and replace existing tissue function. Although most reconstructive efforts still remain in the experimental stage, several technologies have been transferred to the bedside with satisfactory outcome. In this article, we describe tissue engineering approaches attempted in the genitourinary system for reconstruction.
Assuntos
Engenharia Biomédica , Sistema Urogenital , Animais , Feto , Terapia Genética/métodos , Genitália , Humanos , Rim , Ureter , Uretra , Bexiga UrináriaRESUMO
Organ transplantation in an orthotopic location is the current treatment for end-stage organ failure. However, the need for transplantable organs far exceeds the number of available donor organs. As a result, new options, such as tissue engineering and regenerative medicine, have been explored to achieve functional organ replacement. Although there have been many advances in the laboratory leading to the reconstruction of tissue and organ structures in vitro, these efforts have fallen short of producing organs that contain intact vascular networks capable of nutrient and gas exchange and are suitable for transplantation. Recently, advances in whole organ decellularization techniques have enabled the fabrication of scaffolds for engineering new organs. These scaffolds, consisting of naturally-derived extracellular matrix (ECM), provide biological signals and maintain tissue microarchitecture, including intact vascular systems that could integrate into the recipient's circulatory system. The decellularization techniques have led to the development of scaffolds for multiple organs, including the heart, liver, lung and kidney. While the experimental studies involving the use of decellularized organ scaffolds are encouraging, the translation of whole organ engineering into the clinic is still distant. This paper reviews recently described techniques used to decellularize whole organs such as the heart, lung, liver and kidney and describes possible methods for using these matrices for whole organ engineering.
Assuntos
Órgãos Bioartificiais , Bioengenharia/métodos , Separação Celular/métodos , Transplante de Órgãos/métodos , Alicerces Teciduais , Animais , Materiais Biocompatíveis/química , Bioengenharia/tendências , Transplante de Coração , Humanos , Transplante de Rim , Transplante de Fígado , Fígado Artificial , Transplante de Pulmão , Teste de Materiais , Transplante de Órgãos/tendências , Alicerces Teciduais/químicaRESUMO
Soft tissue reconstruction is often needed after massive traumatic damage or cancer removal. In this study, we developed a novel hybrid hydrogel system consisting of alginate particles and a fibrin matrix that could maintain tissue volume long term. Alginate particles were fabricated by mixing 5% alginate with a 20 mM calcium solution. Cells and these alginate particles were then embedded in fibrin (alginate-fibrin) hydrogels using a dual syringe mixer. Cell-hydrogel constructs were evaluated in terms of cell survival and proliferation in the constructs in vitro. The results indicated that cellular viability, spreading and proliferation in the alginate-fibrin hydrogels were significantly higher compared to constructs fabricated with fibrin or alginate only. In vivo explants showed that cells contained within fibrin-only hydrogels did not contribute to neo-tissue formation, and the fibrin was fully degraded within a 12 week period. In the alginate-fibrin system, higher cellularity and vascular ingrowth were observed in vivo. This resulted in neo-tissue formation in the alginate-fibrin hydrogels. These results demonstrate that fibrin may enhance cell proliferation and accelerate the formation of extracellular matrix proteins in the alginate-fibrin system, while the alginate particles could contribute to volume retention. This injectable hybrid system composed of degradable and non-degradable hydrogels may be a preferable approach to the repair of soft tissue defects.
Assuntos
Alginatos/administração & dosagem , Materiais Biocompatíveis/administração & dosagem , Fibrina/administração & dosagem , Engenharia Tecidual/métodos , Proliferação de Células , Células Cultivadas , Humanos , Hidrogéis/administração & dosagem , Injeções , Teste de Materiais , Lesões dos Tecidos Moles/terapia , TransplantesRESUMO
Electrospun fibrous scaffolds have now been shown to possess great potential for tissue engineering applications, owing to their unique mimicry of natural extracellular matrix structure. In this study, poly(ε-caprolactone) and gelatin were electrospun to fabricate tissue-engineered scaffolds with three different fiber morphologies (1.0 µm, 3.0 µm and co-electrospun containing both 1.0 and 3.0 µm diameter fibers). Subsequently, these scaffolds were conjugated with heparin to immobilize a bioactive molecule by electrostatic interactions. This study determined the quantity of heparin conjugation on the scaffolds and that the crosslinking time and the fiber morphologies govern the extent of heparin conjugation on the fibers. In order to evaluate the release capacity of the heparin-conjugated scaffolds, lysozyme was used as a model protein for conjugation. The heparin-conjugated scaffolds provided high loading efficiency and cumulative release of lysozyme with a relatively linear relationship. In addition, the release kinetics was significantly dependent on heparin conjugation and fiber morphology. This fundamental investigation into how fiber morphology and crosslinking protocols can affect the heparin binding ability of electrospun fibers is crucial for predicting the delivery of many different types of bioactive molecules from an electrospun scaffold for tissue engineering applications.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Gelatina/farmacologia , Heparina/farmacologia , Muramidase/administração & dosagem , Miócitos de Músculo Liso/citologia , Poliésteres/farmacologia , Engenharia Tecidual/métodos , Aminas/química , Animais , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Enzimas Imobilizadas/metabolismo , Gelatina/química , Heparina/química , Humanos , Cinética , Fenômenos Mecânicos/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Poliésteres/química , Sus scrofa , Fatores de Tempo , Alicerces Teciduais/químicaAssuntos
Transplante de Células/métodos , Procedimentos de Cirurgia Plástica/métodos , Engenharia Tecidual/métodos , Engenharia Tecidual/tendências , Anormalidades Urogenitais/cirurgia , Sistema Urogenital/cirurgia , Animais , Transplante de Células/tendências , Modelos Animais de Doenças , Feminino , Feto/anormalidades , Feto/patologia , Feto/cirurgia , Terapia Genética/métodos , Terapia Genética/tendências , Humanos , Masculino , Procedimentos de Cirurgia Plástica/tendências , Anormalidades Urogenitais/patologia , Anormalidades Urogenitais/fisiopatologia , Sistema Urogenital/patologia , Sistema Urogenital/fisiopatologiaRESUMO
To evaluate the role of preoperative bone scintigraphy in determining the operative treatment method for femoral neck fracture, we reviewed the data of 83 patients who underwent preoperative bone scanning after femoral neck fracture. Fractures were classified using the Garden staging system. Radioisotope uptake in femoral heads was evaluated visually. Of 28 patients with Garden stage I or II, radioactivity of the femoral head was normal in 26, partially reduced in one, and generally reduced in one patient. Twenty-seven patients were treated by closed reduction and multiple pinning, and one patient was treated by bipolar hemiarthroplasty. Of 55 patients with Garden stage III or IV, femoral-head radioactivity was normal in three, partially reduced in seven and generally reduced in 45 patients. Fifty-four patients were treated by bipolar hemiarthroplasty or total hip arthroplasty, and one patient was treated by closed reduction and multiple pinning. In only one of the 83 cases was the operative method changed because of bone scan findings. Isotope uptake of the femoral head after femoral neck fracture generally corresponded with the degree of fracture displacement. Preoperative bone scans appear to have no significant role to play in determining the operative treatment method for femoral neck fracture.
Assuntos
Fraturas do Colo Femoral/diagnóstico por imagem , Cabeça do Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Cuidados Pré-Operatórios/métodos , Medronato de Tecnécio Tc 99m , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Colo Femoral/metabolismo , Cabeça do Fêmur/metabolismo , Colo do Fêmur/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Cintilografia , Medronato de Tecnécio Tc 99m/farmacocinéticaRESUMO
PURPOSE: Presently gene delivery is most effectively achieved by ex vivo gene transfer, which includes removal of the target tissue, in vitro gene delivery to the target cells, possible selection to enhance the proportion of transfected cells and reintroduction of the gene modified cells. Reintroduction of transformed cells in vivo has been a challenging task. Based on the feasibility of tissue engineering techniques in which cells seeded on biodegradable polymer scaffolds form tissue when implanted in vivo, we explored the possibility of developing a neo-organ system for in vivo gene therapy. MATERIALS AND METHODS: Normal human urothelial cells were harvested, expanded in vitro and seeded on biodegradable polymer scaffolds. The cell-polymer complex was then transfected with PGL3-luc, pCMV-luc and pCMV beta-gal promoter reporter gene constructs. The transfected cell-polymer scaffolds were then implanted in athymic mice and the engineered tissue was retrieved 0, 1, 3, 5 and 7 days after implantation. RESULTS: The reporter gene assay demonstrated an expression of luciferase activity at days 1, 3, 5 and 7 with the peak at day 5. X-gal and beta-galactosidase antibody assays stained positive on the deoxyribonucleic acid treated transfection. CONCLUSIONS: Successful gene transfer can be achieved using biodegradable polymer scaffolds as a urothelial cell delivery vehicle. The transfected cell-polymer scaffold forms an organ-like structure with functional expression of the transfected genes. This study demonstrates that urothelial tissue engineered gene transfer is safe and effective.
Assuntos
Técnicas de Cultura de Órgãos/métodos , Transfecção/métodos , Urotélio , Animais , Células Cultivadas , Estudos de Viabilidade , Vetores Genéticos , Humanos , Camundongos , Camundongos NusRESUMO
PURPOSE: Bladder behavior after refunctionalization is usually unpredictable. We comparatively analyze various aspects of bladder defunctionalization and subsequent refunctionalization using an animal model. MATERIALS AND METHODS: A total of 18 rabbits were divided equally into 3 groups. Animals in group 1 underwent 2 successive surgical procedures, including bladder division and reattachment. Bladder division was performed by hemisecting the bladder from dome to trigone into a functioning and nonfunctioning chamber. Bladder reattachment was achieved by reanastomosing both hemibladders. Group 2 animals underwent sham operations, and group 3 animals were age matched normal controls. Serial urodynamic studies and fluoroscopic cystograms were performed in all animals. Gross, histochemical (hematoxylin and eosin, Masson's trichrome and Sirius red) and immunocytochemical (alpha-actin, collagen I and III) analyses, collagen content determination and organ bath studies were performed. RESULTS: The defunctionalized hemibladders demonstrated lower wet weight, capacity and compliance compared to the functional contralateral and normal control bladders. Refunctionalization of the bladders resulted in a progressive recovery of capacity and compliance with time. The bladder contractile response and connective tissue-to-muscle ratio were abnormal in the defunctionalized segments but normalized after bladder refunctionalization. CONCLUSIONS: Defunctionalization results in remarkable alterations in bladder growth, capacity, compliance and distribution of connective tissue. However, these bladders demonstrate an innate capacity to recover from these alterations following refunctionalization.