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IMPORTANCE: Approximately 20% of individuals infected with SARS-CoV-2 experienced long-term health effects, as defined PCC. However, it is unknown if there are any early biomarkers associated with PCC or whether early intervention treatments may decrease the risk of PCC. In a secondary analysis of a randomized clinical trial, this study demonstrates that among outpatients with SARS-CoV-2, increased IL-6 at time of infection is associated with increased odds of PCC. In addition, among individuals treated early, within 5 days of symptom onset, with COVID-19 convalescent plasma, there was a trend for decreased odds of PCC after adjusting for other demographic and clinical characteristics. Future treatment studies should be considered to evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , SARS-CoV-2 , Soroterapia para COVID-19 , Anticorpos , InflamaçãoRESUMO
BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials. STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders. RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 (4.6%) characterized by mild, allergic-type findings of urticaria, and/or pruritus consistent with minor allergic transfusion reactions; the other reported events were attributed to the patients' underlying disease, COVID-19, or vasovagal in nature. We found no difference in the likelihood of allergic transfusion reactions between those receiving CCP versus control plasma (adjusted odds ratio [AOR], 0.75; 95% CI, 0.43-1.31). Risk of urticaria and/or pruritus increased with a pre-existing diagnosis of asthma (AOR, 2.33; 95% CI, 1.16-4.67). We did not observe any CCP-attributed antibody disease enhancement in participants with COVID-19 or increased risk of infection. There were no life-threatening severe transfusion reactions and no patients required hospitalization related to transfusion-associated complications. DISCUSSION: Outpatient plasma administration was safely performed for nearly 1400 participants. CCP is a safe therapeutic option for outpatients at risk of hospitalization from COVID-19.
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COVID-19 , Reação Transfusional , Urticária , Humanos , COVID-19/terapia , COVID-19/etiologia , Soroterapia para COVID-19 , Imunização Passiva/efeitos adversos , Pacientes Ambulatoriais , SARS-CoV-2 , Reação Transfusional/etiologia , Urticária/etiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
AIM: In modern obstetrics, need of labor induction is increasing along with increased caesarean deliveries. Major contributions for these operative deliveries are due to induction failure. This demands a potent labor-inducing agent. Dinoprostone gel is an established method but having some drawbacks. Misoprostol could be an effective alternative to Dinoprostone, but its fetal safety is not yet well established. This study aimed to evaluate the fetal safety of vaginal Misoprostol tablet by measuring fetal heart rate changes during induction of labor. METHODS: This was a single-center randomized controlled trial incorporating 140 term women, equally randomized to get either tablet Misoprostol or Dinoprostone gel. Fetal heart rate patterns were compared in both the groups by continuous cardiotocographic tracing. All the data were analyzed on an intention-to-treat basis. RESULTS: There were no statistically significant changes in fetal heart rate pattern in both Misoprostol and Dinoprostone groups. Vaginal deliveries were statistically higher in Misoprostol group. Neonatal parameters like 1 min Appearance, Pulse, Grimace, Activity, and Respiration score and neonatal intensive care unit admission were comparable, and there was no significant difference in terms of major adverse events and side effects. CONCLUSIONS: Misoprostol is a safe alternative to Dinoprostone gel for induction of labor and found to be more effective labor-inducing agent. In the background of higher caesarean rate, vaginal Misoprostol can be a potential labor-inducing agent especially in a resource poor setting.
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Misoprostol , Ocitócicos , Gravidez , Recém-Nascido , Feminino , Humanos , Dinoprostona/efeitos adversos , Misoprostol/efeitos adversos , Ocitócicos/efeitos adversos , Trabalho de Parto Induzido/métodos , Parto Obstétrico , Cremes, Espumas e Géis Vaginais , Administração IntravaginalRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients. METHODS: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm. RESULTS: Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16). CONCLUSIONS: In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14. CLINICAL TRIALS REGISTRATION: NCT04373460.
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COVID-19 , Humanos , COVID-19/terapia , SARS-CoV-2 , Pacientes Ambulatoriais , Síndrome , Imunização Passiva/efeitos adversos , Soroterapia para COVID-19RESUMO
Background: Post-COVID conditions (PCC) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about early treatment, inflammation, and PCC. Methods: Among 883 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of CCP vs. control plasma with available biospecimens and symptom data, the association between early COVID treatment, cytokine levels and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14 and day 90 using a multiplexed sandwich immuosassay (Mesoscale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between COVID treatment, cytokine levels and PCC were examined using multivariate logistic regression models. Results: One-third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and loss of smell (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis including diabetes, body mass index, race, and vaccine status, female sex (adjusted odds ratio[AOR]=2.70[1.93-3.81]), older age (AOR=1.32[1.17-1.50]), and elevated baseline levels of IL-6 (AOR=1.59[1.02-2.47]) were associated with development of PCC.There was a trend for decreased PCC in those with early CCP treatment (≤5 days after symptom onset) compared to late CCP treatment. Conclusion: Increased IL-6 levels were associated with the development of PCC and there was a trend for decreased PCC with early CCP treatment in this predominately unvaccinated population. Future treatment studies should evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.
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There is an ever-increasing clinical and socioeconomic burden associated with cartilage lesions & osteoarthritis (OA). Its progression, chondrocyte death & hypertrophy are all facilitated by inflamed synovium & joint environment. Due to their capacity to switch between pro- & anti-inflammatory phenotypes, macrophages are increasingly being recognized as a key player in the healing process, which has been largely overlooked in the past. A biomaterial's inertness has traditionally been a goal while developing them in order to reduce the likelihood of adverse reactions from the host organism. A better knowledge of how macrophages respond to implanted materials has made it feasible to determine the biomaterial architectural parameters that control the host response & aid in effective tissue integration. Thus, this review summarizes novel therapeutic techniques for avoiding OA or increasing cartilage repair & regeneration that might be developed using new technologies tuning macrophages into desirable functional phenotypes.
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Materiais Biocompatíveis , Osteoartrite , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Cartilagem/patologia , Humanos , Macrófagos/patologia , Osteoartrite/tratamento farmacológico , Osteoartrite/patologiaRESUMO
Recent developments in the biomedical arena have led to the fabrication of innovative biomaterials by utilizing bioactive molecules obtained from biological wastes released from fruit and beverage processing industries, and fish, meat, and poultry industries. These biological wastes that end up in water bodies as well as in landfills are an affluent source of animal- and plant-derived proteins, bio ceramics and polysaccharides such as collagens, gelatins, chitins, chitosans, eggshell membrane proteins, hydroxyapatites, celluloses, and pectins. These bioactive molecules have been intricately designed into scaffolds and dressing materials by utilizing advanced technologies for drug delivery, tissue engineering, and wound healing relevance. These biomaterials are environment-friendly, biodegradable, and biocompatible, and show excellent tissue regeneration attributes. Additionally, being cost-effective they can reduce the burden on the healthcare system as well as provide a sustainable solution to waste management. In this review, the current trends in the utilization of plant and animal waste-derived biomaterials in various biomedical fields are considered along with a separate section on their applications as xenografts.
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Materiais Biocompatíveis/química , Eliminação de Resíduos Líquidos , Animais , Teste de MateriaisRESUMO
Microorganisms in the rhizosphere are abundant and exist in very high taxonomic diversity. The major players are bacteria and fungi, and bacteria have evolved many strategies to prevail over fungi, among them harmful enzyme activities and noxious secondary metabolites. Interactions between plant growth promoting rhizobacteria and phytopathogenic fungi are potentially valuable since the plant would benefit from fungal growth repression. In this respect, the role of volatile bacterial metabolites in fungistasis has been demonstrated, but the mechanisms of action are less understood. We used three phytopathogenic fungal species (Sclerotinia sclerotiorum, Rhizoctonia solani, and Juxtiphoma eupyrena) as well as one non-phytopathogenic species (Neurospora crassa) and the plant growth promoting rhizobacterium Serratia plymuthica 4Rx13 in co-cultivation assays to investigate the influence of bacterial volatile metabolites on fungi on a cellular level. As a response to the treatment, we found elevated lipid peroxidation, which indirectly reflected the loss of fungal cell membrane integrity. An increase in superoxide dismutase, catalase, and laccase activities indicated oxidative stress. Acclimation to these adverse growth conditions completely restored fungal growth. One of the bioactive bacterial volatile compounds seemed to be ammonia, which was a component of the bacterial volatile mixture. Applied as a single compound in biogenic concentrations ammonia also caused an increase in lipid peroxidation and enzyme activities, but the extent and pattern did not fully match the effect of the entire bacterial volatile mixture.
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Fungos , Rizosfera , Peroxidação de Lipídeos , Superóxido DismutaseRESUMO
The use of decellularized native allogenic or xenogenic cartilaginous extracellular matrix (ECM) biomaterials is widely expanding in the fields of tissue engineering and regenerative medicine. In this study, we aimed to develop an acellular, affordable, biodegradable, easily available goat conchal cartilaginous ECM derived scaffolding biomaterial for repair and regeneration of osteochondral defects in rabbits. Cartilages harvested from freshly collected goat ears were decellularized using chemical agents, namely, hypotonic-hypertonic (HH) buffer and Triton X-100 solution, separately. The morphologies and ultrastructure orientations of the decellularized cartilages remained unaltered in spite of complete cellular loss. Furthermore, when the acellular cartilaginous ECMs were cultured with murine mesenchymal stem cells (MSCs) (C3H10T1/2 cells), cellular infiltration and proliferation were thoroughly monitored using SEM, DAPI and FDA stained images, whereas the MTT assay proved the biocompatibility of the matrices. The increasing amounts of secreted ECM proteins (collagen and sGAG) indicated successful chondrogenic differentiation of the MSCs in the presence of the treated cartilage samples. In vivo biocompatibility studies showed no significant immune response or tissue rejection in the treated samples but tissue necrosis in control samples after 3 months. Upon implantation of the constructs in rabbits' osteochondral defects for 3 months, the histological and micro-CT evaluation revealed significant enhancement and regeneration of neocartilage and subchondral bony tissues. The IGF-1 loaded cartilaginous constructs showed comparatively better healing response after 3 months. Our results showed that decellularized xenogenic cartilaginous biomaterials preserved the bioactivity and integrity of the matrices that also favored in vitro stem cell proliferation and chondrogenic differentiation and enabled osteochondral regeneration, thus paving a new way for articular cartilage reconstruction.
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Cartilagem Articular/citologia , Cartilagem Articular/fisiologia , Condrogênese , Matriz Extracelular/metabolismo , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Camundongos , CoelhosRESUMO
Because of poor regenerative capabilities of cartilage, reconstruction of similar rigidity and flexibility is difficult, challenging, and restricted. The aim of the present investigation was to develop cost-effective acellular xenogeneic biomaterial as cartilage substitution. Two novel biometrics have been developed using different chemical processes (Na-deoxycholate + SDS and GndHCl + NaOH) to decellularize caprine (goat) ear cartilage and further extensively characterized before preclinical investigation. Complete cell removal was ascertained by hematoxylin and eosin staining followed by DNA estimation. No adverse effect on extracellular matrix (ECM) was found by quantifying collagen and sulfated glycosaminoglycans (sGAG) content as well as collagen, sGAG and elastin staining. Results showed no drastic changes in ECM structure apart from desired sGAG loss. Scanning electron microscopy images confirmed cellular loss and unaltered orientation. Nano-indentation study on cartilage matrices indicated interesting output showing better results among decellularized groups. Increased elastic modulus and hardness indicated better stiffness and more active energy dissipation mechanism due to decellularization. Fluid uptake and retention property remained unchanged after decellularization as analyzed by swelling behavior study. Additionally, acellular materials were confirmed to be nonreactive and nonhemolytic as assessed by in vitro hemocompatibility study. In vivo study (up to 3 months) on rabbits showed no symptoms of graft rejection/ tissue necrosis, established through postoperative histology and biochemical analyses of tissue explants. With regard to size, shape, biomechanics, source of origin and nonimmunogenic properties, these developed materials can play versatile role in biomedical/ clinical applications and pave a new insight as alternatives in cartilage reconstruction.
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Cabras , Engenharia Tecidual , Animais , Cartilagem , Colágeno , Matriz Extracelular , Coelhos , Engenharia Tecidual/métodosRESUMO
The inability of cartilage tissue to self-heal due to its avascular nature often leads to conditions such as osteoarthritis, traumatic rupture of cartilage, and osteochondrosis. The cartilage provides cushioning effects between the joints and avoids bone frictions. The extracellular matrix (ECM) of cartilage consists predominantly of collagens, elastin, proteoglycans and glycoproteins. A number of tissue engineered ECM derived biological scaffolds and matrices are available for cartilage regeneration. The decellularized tissues provide appropriate bioactive cues in the absence of cellular components, hence avoiding immunological issue. However, the decellularization process involves several cellular disruption techniques that may alter the ECM architecture affecting bioactivity. Therefore, development of cell-free cartilage biomaterials with unaltered ECM integrity and bioactivity is of paramount necessity by smart selection of modified techniques and agents. Herein, we described about various decellularization methods, agents, techniques, and their applications in tissue/cartilage decellularization. It also contemplates various difficulties and future perspectives to troubleshoot the existing obstructions in tissue-derived cartilage matrices and their applications.
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Cartilagem/citologia , Matriz Extracelular , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Bovinos , Humanos , Medicina Regenerativa/métodos , Ovinos , SuínosRESUMO
The present study was carried out to evaluate the effect of dynamic loading on bone regeneration performance of different doped ß-tri-calcium phosphate ceramics. We have developed porous beta tri-calcium phosphate (ß-TCP), 5%zinc doped, 5% magnesium doped and 5% titanium doped ß-TCP by aqueous solution combustion technique. All the synthesized ß-TCP powders showed pore size of 21-146⯵m (pure ß-TCP), 16-142⯵m (Zn-ß-TCP), 28-156⯵m (Mg- ß-TCP) and 14-173⯵m (Ti-ß-TCP) while their apparent porosity 17.89%, 28.09%, 26.54% and 25.87% respectively. The pure and doped samples were implanted in femoral bone defect model (rabbit) to assess bone regeneration under dynamic loading. Bone regeneration was assessed after 1 and 2 month post-implantation on the basis of clinical radiological, histological, fluorochrome labelling, micro computed tomography (µ-CT) and scanning electron microscopy (SEM). Radiological and fluorochrome labelling study showed reduced size of 5%Ti-ß-TCPimplant vis-à-vis more new bone formation as compared to other groups. Micro-CT of the implanted bone sample showed a significant amount of newly formed bony tissue surrounding the Ti-ß-TCP implant as compared to other samples. Similar findings of less interfacial gap between the implant and bone were also observed in SEM study. However, all the doped materials are suitable as bone grafting material and have potential for application in bone tissue engineering.
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Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Cerâmica/química , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Regeneração/efeitos dos fármacos , Animais , Feminino , Fêmur/citologia , Fêmur/diagnóstico por imagem , Masculino , Porosidade , Coelhos , Reologia , Suporte de Carga , Microtomografia por Raio-XRESUMO
Mesoporous bioactive glass (MBG) has drawn much attention due to its superior surface texture, porosity and bioactive characteristics. Aim of the present study is to synthesize MBG using different surfactants, viz., hexadecyltrimethylamonium(CTAB) (M1), poly-ethylene glycol (PEG) (M2) and pluronic P123 (M3); bioactivity study; and to understand their bone regeneration efficacy in combination with insulin-like growth factors (IGF-1) in animal bone defect model. SBF study revealed the formation of calcium carbonate (CaCO3) and hydroxyapatite (HAp) phase over 14 days. Formation of apatite layer was further confirmed by FTIR, FESEM and EDX analysis. M1 and M2 showed improved crystallinity, while M3 showed slightly decrease in crystalline peak of CaCO3 and enhanced HAp phase. More Ca-P layer formed in M1 and M2 supported the in vivo experiments subsequently. Degree of new bone formation for all MBGs were high, i.e., M1 (80.7⯱â¯2.9%), M2 (74.4⯱â¯2.4%) and M3 (70.1⯱â¯1.9%) compared to BG (66.9⯱â¯1.8%). In vivo results indicated that the materials were non-toxic, biodegradable, biocompatible, and is suitable as bone replacement materials. Thus, we concluded that growth factor loaded MBG is a promising candidate for bone tissue engineering application.
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Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Vidro/química , Fator de Crescimento Insulin-Like I/química , Animais , Feminino , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Masculino , Porosidade , Coelhos , Microtomografia por Raio-XRESUMO
Restoration of the external ear and nose in human patients, in either congenital deformity or acquired defects, is a challenge in reconstructive surgery. Optimization of the currently available materials is necessary for rhinoplasty and microtia correction to avoid intraoperative manoeuvring and early rejection. The aim of this study was to develop cross-linked decellularized caprine conchal cartilages as biocompatible, robust, and non-toxic matrix template. The characterization of the decellularized tissue encompasses in vitro lymphoproliferation assay, cytotoxicity test, agar gel precipitation test, in vivo immunocompatibility study, histology, and determination of pro-inflammatory cytokines in animal model. Decellularized cartilage was implanted in human volunteer at R. G. Kar Medical College and Hospital, Kolkata, India, and samples were assessed histologically by retrieving those after 4 months. The processed cartilages were implanted in rhinoplasty (nine) and microtia patients (six) keeping autogenous cartilage graft as control up to 18 months after surgery. Primary outcomes were viability and safety of the material, both in animal model and human pre-application in actual site. Secondary outcomes included self-assessed clinical findings on gross examination. This study is under the ethical approval no. RKC/14 dated January 27, 2012. The in vitro cellular reactivity was less in processed cartilage protein than control. Histology of retrieved tissues in animal model and human volunteer showed no adverse reactions. Production of IL-2, IL-6, and TNF-α cytokines was lower at 4 weeks. The rhinoplasty and microtia operation in clinical patients utilizing the processed cartilage showed satisfactory recovery with improved facial look. These low cost, easily available, biocompatible, safe xenocartilage biomatrices of caprine conchal cartilage origin are very flexible in shape and size, enabling them as potential bioimplant for repair of nasal and auricular structure without any rejection or diverse biomedical applications.
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Bioprótese , Cartilagem/transplante , Cartilagem da Orelha/transplante , Nariz , Rinoplastia , Adulto , Animais , Feminino , Cabras , Humanos , Nariz/patologia , Nariz/cirurgiaRESUMO
A new generation of nanostructured glasses called mesoporous bioactive glasses (MBGs) exhibit superior surface texture, porosity and bioactive characteristics. The present study is carried out to develop and detailed characterize of ternary SiO2-CaO-P2O5 MBG structure, fabricated by three different variations using different surfactants, e.g., hexadecyltrimethylammonium bromide (CTAB), poly-ethylene glycol,(PEG) and Pluronic P123. After thorough physico-chemical characterization, MBG granules were investigated for in vivo bone regeneration in animal bone defect model (rabbit) where standard S53P4 bioactive glass was used as control. All the synthesized MBG powders showed nano-range median particle size of 80-120â¯nm (MBG-CTAB), 50-70â¯nm (MBG-PEG and MBG-P123) while their specific surface area as 473.2, 52.2 and 169.3â¯m2/g respectively. All MBGs showed mesoporous nature corroborating transmission electron microscopy (TEM) observation as well. Bone regeneration property was measured after 45 and 90 days post-implantation at distal epiphysis of rabbit femur by radiography, histology, fluorochrome labeling, micro computed tomography (micro-CT) and vital organ histology. Results from in vivo studies indicated that the MBG materials produce minimal toxicity to the body. Furthermore, the biocompatibility and biodegradability of the implant makes them more suitable for application in bone tissue engineering. Among various implants, MBG fabricated using suitable surfactant (CTAB) shown the best result compared to other implants. Nonetheless, all the materials are suitable for application in bone tissue engineering and have potential for bone regeneration and healing.
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Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Vidro/química , Teste de Materiais , Animais , Materiais Biocompatíveis/toxicidade , Compostos de Cálcio/química , Fêmur/citologia , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Óxidos/química , Fosfatos/química , Porosidade , Coelhos , Dióxido de Silício/química , Engenharia Tecidual , Alicerces Teciduais/química , Microtomografia por Raio-XRESUMO
Repair and regeneration of nasal and auricular cartilage thrust significant challenges in reconstructive surgery. The burgeoning clinical requirement is yet to endorse a satisfactory cartilage replacement matrix. In this regard, we have bioengineered cross-linked decellularized caprine conchal cartilage (DC) as biocompatible, durable, and nontoxic matrices. The DC matrices exhibited reduced DNA and sulfated glycosaminoglycan (sGAG) with a minimal effect on the collagen content. Further, histology and scanning electron micrographs revealed a significant loss of cellular bodies and the presence of a compact matrix consisting of intricate collagen fibers, when compared to unprocessed matrices. An in vitro biological assessment of the matrices exhibited an increased chondrocyte proliferation and viability with a significantly higher DNA, sGAG, and total collagen content. The matrices showed a 3-fold increase in the expression of cartilage-specific genes, namely, aggrecan, collagen II, and sox-9, and exhibited a minimal in vitro immunogenicity. Further, an in vivo assessment was performed by xenografting these caprine matrices in a rabbit model. The retrieved matrices showed a well-organized structural and cellular orientation with extracellular matrix formation after 3 months of implantation. No significant infiltration of plasma cells, macrophages, lymphocytes, and immature fibroblasts was recorded. Therefore, these affordable, resourceful, xenocompatible matrices offer a potential alternate in the repair and regeneration of nasal and auricular cartilages.
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Complex cutaneous wounds like diabetic foot ulcers represent a critical clinical challenge and demand a large-scale and low-cost strategy for effective treatment. Herein, we use a rabbit animal model to investigate efficacy of bioactive wound dressings made up of silk biomaterials. Nanofibrous mats of Antheraea assama silkworm silk fibroin (AaSF) are coated with various recombinant spider silk fusion proteins through silk-silk interactions to fabricate multifunctional wound dressings. Two different types of spider silk coatings are used to compare their healing efficiency: FN-4RepCT (contains a cell binding motif derived from fibronectin) and Lac-4RepCT (contains a cationic antimicrobial peptide from lactoferricin). AaSF mats coated with spider silk show accelerated wound healing properties in comparison to the uncoated mats. Among the spider silk coated variants, dual coating of FN-4RepCT and Lac-4RepCT on top of AaSF mat demonstrated better wound healing efficiency, followed by FN-4RepCT and Lac-4RepCT single coated counterparts. The in vivo study also reveals excellent skin regeneration by the functionalized silk dressings in comparison to commercially used Duoderm dressing and untreated wounds. The spider silk coatings demonstrate early granulation tissue development, re-epithelialization, and efficient matrix remodelling of wounds. The results thus validate potential of bioactive silk matrices in faster repair of diabetic wounds.
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In recent years the potential application of nanocomposite biomaterials in tissue engineering field is gaining importance because of the combined features of all the individual components. A bottom-up approach is acquired in this study to recreate the bone microenvironment. The regenerated silk protein fibroin obtained from nonmulberry tropical tasar Antheraea mylitta species is reinforced with functionalized carbon nano fiber (CNF) and the composite sponges are fabricated using facile green aqueous based method. Biophysical investigations show that the matrices are porous and simultaneously bioactive when incubated in simulated body fluid. The reinforcement of CNF influences the mechanical property of the matrices by increasing the compressive modulus up to 46.54 MPa (â¼4.3 times of the control fibroin sponge) in hydrated state, which is higher than the minimum required human trabecular bone modulus (10 MPa). The composite matrices are found to be non-hemolytic as well as cytocompatible. The growth factors (BMP-2 and TGF-ß1) loaded composites show sustained release kinetics and an early attachment, growth, proliferation, and osteogenic differentiation of the osteoblasts and mesenchymal stem cells. The matrices are immunocompatible as evidenced by minimal release of pro-inflammatory cytokines both in vitro and in vivo. In order to support the in vitro study, in vivo analysis of new bone formation within the implants is performed through radiological, µ-CT, fluorochrome labeling and histological analysis, which show statistically better bone formation on growth factor loaded composite scaffolds. The study clearly shows the potential attributes of these composite matrices as an extra cellular matrix for supporting successful osseointegration process.
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Proteína Morfogenética Óssea 2/administração & dosagem , Regeneração Óssea , Preparações de Ação Retardada/química , Fibroínas/química , Nanofibras/química , Alicerces Teciduais/química , Fator de Crescimento Transformador beta1/administração & dosagem , Animais , Bombyx , Proteína Morfogenética Óssea 2/farmacologia , Regeneração Óssea/efeitos dos fármacos , Linhagem Celular , Feminino , Humanos , Masculino , Teste de Materiais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Coelhos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Engenharia Tecidual/métodos , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
INTRODUCTION: Early Clinical Exposure has been conceptualized to orient medical students towards actual clinical scenario and help them correlate their theoretical knowledge with real life situations in early years of MBBS courses. In the present study we explored the outcome of early clinical exposure in the context of basic science topics (Physiology) in fresh MBBS entrants and compared their performance with a conventionally taught control group. METHODS: One hundred fifty voluntary students of 1st year MBBS (2015-16) batch consisted the sample of this study. They were divided into two groups through the simple random method (using computer generated random number table with roll numbers of the students). They were evaluated by MCQ (Multiple Choice Question) and OSCE (Objective Structured Clinical Examination) before and after being taught a basic Physiology topic (respiratory system) theoretically. The study group underwent clinical exposure before the post-test while the control group did not. Performance of the students was compared between the two groups by unpaired student's t-test whereas marks of pre and post-test within the same group were compared by paired Student's t-test. Everywhere p<0.05 was considered to be significant. RESULTS: The marks of each group in the pre and post-tests differed significantly (P<0.05 in each case). Post-test marks were significantly greater in each group though the level of improvement was strikingly higher in the study group (p=0.01). Though there was no significant difference in pre-test marks of both groups (P=0.73), post-test marks were significantly higher in the study group (P=0.04). Among the exposed students, majority (92%) opined that ECE was a better technique being practically oriented and more interesting while some (8%) found it to be more time and energy-consuming, suitable for selective portions of basic science topics. CONCLUSION: Early clinical exposure may be an effective technique to supplement the traditional theoretical teaching and improve the performance of fresh medical entrants in Physiology. It has better acceptability by the students and may be considered for inclusion in the existing pre-clinical curriculum with proper allocation of time and manpower.