scholarly journals Tissue Engineered Scaffolds for an Effective Healing and Regeneration: Reviewing Orthotopic Studies

2014 ◽  
Vol 2014 ◽  
pp. 1-27 ◽  
Author(s):  
Silvia Baiguera ◽  
Luca Urbani ◽  
Costantino Del Gaudio

It is commonly stated that tissue engineering is the most promising approach to treat or replace failing tissues/organs. For this aim, a specific strategy should be planned including proper selection of biomaterials, fabrication techniques, cell lines, and signaling cues. A great effort has been pursued to develop suitable scaffolds for the restoration of a variety of tissues and a huge number of protocols ranging fromin vitrotoin vivostudies, the latter further differentiating into several procedures depending on the type of implantation (i.e., subcutaneous or orthotopic) and the model adopted (i.e., animal or human), have been developed. All together, the published reports demonstrate that the proposed tissue engineering approaches spread toward multiple directions. The critical review of this scenario might suggest, at the same time, that a limited number of studies gave a real improvement to the field, especially referring toin vivoinvestigations. In this regard, the present paper aims to review the results ofin vivotissue engineering experimentations, focusing on the role of the scaffold and its specificity with respect to the tissue to be regenerated, in order to verify whether an extracellular matrix-like device, as usually stated, could promote an expected positive outcome.

1995 ◽  
Vol 9 (3) ◽  
pp. 255-269 ◽  
Author(s):  
G.H. Bowden

Models of the caries process have made significant contributions toward defining the roles of bacteria in caries. Microbiologists use a variety of in vitro systems to model aspects of the caries process. Also, in situ models in humans provide information on the microbiology of caries in vivo. These models do not involve the entire process leading to natural caries; consequently, the results from such studies are used to deduce the roles of bacteria in natural caries. Therefore, they can be described as Inferential Caries Models. In contrast, animal models and some clinical trials in humans involve natural caries and can be described as Complete Caries Models. Furthermore, these models are used in two distinct ways. They can be used as Exploratory Models to explore different aspects of the caries process, or as Test Models to determine the effects of anticaries agents. This dichotomy in approach to the use of caries models results in modification of the models to suit a particular role. For example, if we consider Exploratory Models, the in situ appliance in humans is superior to others for analyzing the microbiology of plaque development and demineralization in vivo. The chemostat and biofilm models are excellent for exploring factors influencing bacterial interactions. Both models can also be used as Test Models. The in situ model has been used to test the effects of fluoride on the microflora and demineralization, while the chemostat and biofilm models allow for the testing of antibacterial agents. Each model has its advantages and disadvantages and role in analysis of the caries process. Selection of the model depends on the scientific question posed and the limitations imposed by the conditions available for the study.


2009 ◽  
Vol 53 (6) ◽  
pp. 2463-2468 ◽  
Author(s):  
Patrizia Spigaglia ◽  
Fabrizio Barbanti ◽  
Thomas Louie ◽  
Frédéric Barbut ◽  
Paola Mastrantonio

ABSTRACT Recent studies have suggested that exposure to fluoroquinolones represents a risk factor for the development of Clostridium difficile infections and that the acquisition of resistance to the newer fluoroquinolones is the major reason facilitating wide dissemination. In particular, moxifloxacin (MX) and levofloxacin (LE) have been recently associated with outbreaks caused by the C. difficile toxinotype III/PCR ribotype 027/pulsed-field gel electrophoresis type NAP1 strain. In this study, we evaluated the potential of MX and LE in the in vitro development of fluoroquinolone resistance mediated by GyrA and GyrB alterations. Resistant mutants were obtained from five C. difficile parent strains, susceptible to MX, LE, and gatifloxacin (GA) and belonging to different toxinotypes, by selection in the presence of increasing concentrations of MX and LE. Stable mutants showing substitutions in GyrA and/or GyrB were obtained from the parent strains after selection by both antibiotics. Mutants had MICs ranging from 8 to 128 μg/ml for MX, from 8 to 256 μg/ml for LE, and from 1.5 to ≥32 μg/ml for GA. The frequency of mutation ranged from 3.8 × 10−6 to 6.6 × 10−5 for MX and from 1.0 × 10−6 to 2.4 × 10−5 for LE. In total, six different substitutions in GyrA and five in GyrB were observed in this study. The majority of these substitutions has already been described for clinical isolates or has occurred at positions known to be involved in fluoroquinolone resistance. In particular, the substitution Thr82 to Ile in GyrA, the most common found in resistant C. difficile clinical isolates, was observed after selection with LE, whereas the substitution Asp426 to Val in GyrB, recently described in toxin A-negative/toxin B-positive epidemic strains, was observed after selection with MX. Interestingly, a reduced susceptibility to fluoroquinolones was observed in colonies isolated after the first and second steps of selection by both MX and LE, with no substitution in GyrA or GyrB. The results suggest a relevant role of fluoroquinolones in the emergence and selection of fluoroquinolone-resistant C. difficile strains also in vivo.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Linli Li ◽  
Yiqun He ◽  
Han Tang ◽  
Wei Mao ◽  
Haofei Ni ◽  
...  

Background. Angiogenesis is a prerequisite step to achieve the success of bone regeneration by tissue engineering technology. Previous studies have shown the role of cerebrospinal fluid pulsation (CSFP) stress in the reconstruction of tissue-engineered laminae. In this study, we investigated the role of CSFP stress in the angiogenesis of tissue-engineered laminae. Methods. For the in vitro study, a CSFP bioreactor was used to investigate the impact of CSFP stress on the osteogenic mesenchymal stem cells (MSCs). For the in vivo study, forty-eight New Zealand rabbits were randomly divided into the CSFP group and the Non-CSFP group. Tissue-engineered laminae (TEL) was made by hydroxyapatite-collagen I scaffold and osteogenic MSCs and then implanted into the lamina defect in the two groups. The angiogenic and osteogenic abilities of newborn laminae were examined with histological staining, qRT-PCR, and radiological analysis. Results. The in vitro study showed that CSFP stress could promote the vascular endothelial growth factor A (VEGF-A) expression levels of osteogenic MSCs. In the animal study, the expression levels of angiogenic markers in the CSFP group were higher than those in the Non-CSFP group; moreover, in the CSFP group, their expression levels on the dura mater surface, which are closer to the CSFP stress stimulation, were also higher than those on the paraspinal muscle surface. The expression levels of osteogenic markers in the CSFP group were also higher than those in the Non-CSFP group. Conclusion. CSFP stress could promote the angiogenic ability of osteogenic MSCs and thus promote the angiogenesis of tissue-engineered laminae. The pretreatment of osteogenic MSC with a CSFP bioreactor may have important implications for vertebral lamina reconstruction with a tissue engineering technique.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Susan D'Souza ◽  
Jabar A. Faraj ◽  
Stefano Giovagnoli ◽  
Patrick P. DeLuca

In this study, four PLGA microsphere formulations of Olanzapine were characterized on the basis of theirin vitrobehavior at 37°C, using a dialysis based method, with the goal of obtaining an IVIVC.In vivoprofiles were determined by deconvolution (Nelson-Wagner method) and using fractional AUC. Thein vitroandin vivorelease profiles exhibited the same rank order of drug release. Further,in vivoprofiles obtained with both approaches were nearly superimposable, suggesting that fractional AUC could be used as an alternative to the Nelson-Wagner method. A comparison of drug release profiles for the four formulations revealed that thein vitroprofile lagged slightly behindin vivorelease, but the results were not statistically significant (P<0.0001). Using the four formulations that exhibited different release rates, a Level A IVIVC was established using the deconvolution and fractional AUC approaches. A nearly 1 : 1 correlation (R2>0.96) betweenin vitrorelease andin vivomeasurements confirmed the excellent relationship betweenin vitrodrug release and the amount of drug absorbedin vivo. The results of this study suggest that proper selection of anin vitromethod will greatly aid in establishing a Level A IVIVC for long acting injectables.


Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1580 ◽  
Author(s):  
Vuanghao Lim ◽  
Edward Schneider ◽  
Hongli Wu ◽  
Iok-Hou Pang

Cataract is an eye disease with clouding of the eye lens leading to disrupted vision, which often develops slowly and causes blurriness of the eyesight. Although the restoration of the vision in people with cataract is conducted through surgery, the costs and risks remain an issue. Botanical drugs have been evaluated for their potential efficacies in reducing cataract formation decades ago and major active phytoconstituents were isolated from the plant extracts. The aim of this review is to find effective phytoconstituents in cataract treatments in vitro, ex vivo, and in vivo. A literature search was synthesized from the databases of Pubmed, Science Direct, Google Scholar, Web of Science, and Scopus using different combinations of keywords. Selection of all manuscripts were based on inclusion and exclusion criteria together with analysis of publication year, plant species, isolated phytoconstituents, and evaluated cataract activities. Scientists have focused their attention not only for anti-cataract activity in vitro, but also in ex vivo and in vivo from the review of active phytoconstituents in medicinal plants. In our present review, we identified 58 active phytoconstituents with strong anti-cataract effects at in vitro and ex vivo with lack of in vivo studies. Considering the benefits of anti-cataract activities require critical evaluation, more in vivo and clinical trials need to be conducted to increase our understanding on the possible mechanisms of action and the therapeutic effects.


2021 ◽  
Author(s):  
Yuan Zhu ◽  
Xiao Zhang ◽  
Kunkun Yang ◽  
Yuzi Shao ◽  
Ranli Gu ◽  
...  

Abstract Background In tissue engineering, mesenchymal stem cells (MSCs) are common seed cells because of abundant sources, strong proliferation ability and immunomodulatory function. Numerous researches have demonstrated that MSC-macrophage crosstalk played a key role in the tissue engineering. Macrophages could regulate the differentiation of MSCs via different molecular mechanisms, including extracellular vesicles. Apoptotic macrophages could generate large amounts of apoptotic vesicles (apoVs), whereas the functions of macrophage-derived apoVs remain largely unknown. There was no research to clarify the role of macrophage-derived apoVs in MSC fate choices. In this study, we aimed to characterize macrophage-derived apoVs, and investigate the roles of macrophage-derived apoVs in the fate commitment of MSCs. Methods We characterized macrophage-derived apoVs, and investigated their role in MSC osteogenesis and adipogenesis in vitro and in vivo. Furthermore, we performed microRNA loss- and gain- of function experiments and western blot to determine the molecular mechanism. Results We found that macrophage-derived apoVs inhibited osteogenesis and promoted adipogenesis in vitro and in vivo. In mechanism, apoVs regulated osteogenesis and adipogenesis of MSCs by delivering microRNA155 (miR155). Conclusions Macrophage-derived apoVs could regulate the osteogenesis and adipogenesis of MSCs through delivering miR155, which provided novel insights for MSC-mediated tissue engineering.


Author(s):  
Evgeniy Borodin

A search was carried out for potential ligands to TRPM8 - a representative of the family of cationic channels with a transient receptor potential involved in the development of bronchial hypersensitivity and the occurrence of bronchospasm in response to low temperatures. We used a structural design and molecular docking using the autodock software package (http://autodock.scripps.edu/), which allows automated testing of many potential ligands for TRPM8. Docking was carried out with tyrosine 745 (Y745) amino acid residue as a critical residue for channel sensitivity to menthol, a classic TRPM8 agonist. The selection of potential candidates for the role of drugs intended for the treatment of bronchial cold hyperreactivity using in silico methods can be supplemented by testing their biological activity in vitro experiments with cell and tissue cultures and in vivo with experimental animals.


Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 940
Author(s):  
João Meneses ◽  
João C. Silva ◽  
Sofia R. Fernandes ◽  
Abhishek Datta ◽  
Frederico Castelo Ferreira ◽  
...  

The use of digital twins in tissue engineering (TE) applications is of paramount importance to reduce the number of in vitro and in vivo tests. To pursue this aim, a novel multimodal bioreactor is developed, combining 3D design with numerical stimulation. This approach will facilitate the reproducibility between studies and the platforms optimisation (physical and digital) to enhance TE. The new bioreactor was specifically designed to be additive manufactured, which could not be reproduced with conventional techniques. Specifically, the design suggested allows the application of dual stimulation (electrical and mechanical) of a scaffold cell culture. For the selection of the most appropriate material for bioreactor manufacturing several materials were assessed for their cytotoxicity. Numerical modelling methods were then applied to the new bioreactor using one of the most appropriate material (Polyethylene Terephthalate Glycol-modified (PETG)) to find the optimal stimulation input parameters for bone TE based on two reported in vitro studies.


2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


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