scholarly journals Gastrointestinal synthetic epithelial linings

2020 ◽  
Vol 12 (558) ◽  
pp. eabc0441
Author(s):  
Junwei Li ◽  
Thomas Wang ◽  
Ameya R. Kirtane ◽  
Yunhua Shi ◽  
Alexis Jones ◽  
...  
Keyword(s):  
Drug Absorption ◽  
Ex Vivo ◽  
The Body ◽  
Proof Of Concept ◽  
Barrier Formation ◽  
Synthetic Biomaterial ◽  
Gastrointestinal Epithelium ◽  
Essential Enzyme ◽  
Directed Polymerization

Epithelial tissues line the organs of the body, providing an initial protective barrier as well as a surface for nutrient and drug absorption. Here, we identified enzymatic components present in the gastrointestinal epithelium that can serve as selective means for tissue-directed polymerization. We focused on the small intestine, given its role in drug and nutrient absorption and identified catalase as an essential enzyme with the potential to catalyze polymerization and growth of synthetic biomaterial layers. We demonstrated that the polymerization of dopamine by catalase yields strong tissue adhesion. We characterized the mechanism and specificity of the polymerization in segments of the gastrointestinal tracts of pigs and humans ex vivo. Moreover, we demonstrated proof of concept for application of these gastrointestinal synthetic epithelial linings for drug delivery, enzymatic immobilization for digestive supplementation, and nutritional modulation through transient barrier formation in pigs. This catalase-based approach to in situ biomaterial generation may have broad indications for gastrointestinal applications.

scholarly journals Potentially toxic metallic wear nanoparticles and trace metal ions release from metal-on-metal orthopedic implants in the human biological specimens: An Overview of in vivo and ex vivo clinical studies

2020 ◽  
Vol 8 (3) ◽  
pp. 242-292
Author(s):  
Henryk Matusiewicz ◽  
Magdalena Richter
Keyword(s):  
Trace Metal ◽  
Metal Ions ◽  
Ex Vivo ◽  
Orthopedic Implants ◽  
The Body ◽  
Trace Metal Ions ◽  
Bodily Fluids ◽  
Metal On Metal

The use of metallic biomaterials in the medical implant devices has become increasingly prevalent over the past few decades. Patients find themselves being exposed to metals in a variety of ways, ranging from external exposure to instruments such as medical devices to internal exposure via surgical devices being implanted in their bodies. In situ generation of metallic wear nanoparticles, corrosion products and in vivo trace metal ions release from metal and metallic alloys implanted into the body in orthopedic surgery is becoming a major cause for concern regarding the health and safety of patients. The chemical form, particulate vs. ionic, of the metal species in the bodily fluids and tissues is a key to the local nanotoxicity effects arising in the body. Potential health risks are associated with metallic wear debris in the form of nanoparticles in situ generation and the release of in vivo trace metal ions into human biological specimen's circulation. This overview explores how migration of metallic wear nanoparticles and ultratrace metal ions in the area of metal-on-metal orthopedic implants influences the surrounding tissues and bodily fluids, and what the toxicological consequences of this process may be. Specifically, the present article is more informative of indicative multilevel in situ/in vivo/ex vivo analytical/clinical methodologies which will be helpful in a way to plan, understand and lead the analytical innovations in the area of nano-analysis to improve patient outcomes.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

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.

Scaffolds for Drug Delivery in Tissue Engineering

2008 ◽  
Vol 1 (2) ◽  
pp. 113-123 ◽  
Author(s):  
Vikas V. Gaikwad ◽  
Abasaheb B. Patil ◽  
Madhuri V. Gaikwad
Keyword(s):  
Drug Delivery ◽  
Tissue Engineering ◽  
Heart Diseases ◽  
Cartilage Regeneration ◽  
Tissue Growth ◽  
The Body ◽  
Patient Specific ◽  
In Situ Gel ◽  
Heart Muscle Cells

Scaffolds are used for drug delivery in tissue engineering as this system is a highly porous structure to allow tissue growth.  Although several tissues in the body can regenerate, other tissue such as heart muscles and nerves lack regeneration in adults. However, these can be regenerated by supplying the cells generated using tissue engineering from outside. For instance, in many heart diseases, there is need for heart valve transplantation and unfortunately, within 10 years of initial valve replacement, 50–60% of patients will experience prosthesis associated problems requiring reoperation. This could be avoided by transplantation of heart muscle cells that can regenerate. Delivery of these cells to the respective tissues is not an easy task and this could be done with the help of scaffolds. In situ gel forming scaffolds can also be used for the bone and cartilage regeneration. They can be injected anywhere and can take the shape of a tissue defect, avoiding the need for patient specific scaffold prefabrication and they also have other advantages. Scaffolds are prepared by biodegradable material that result in minimal immune and inflammatory response. Some of the very important issues regarding scaffolds as drug delivery systems is reviewed in this article.

scholarly journals Ferromagnetic soft catheter robots for minimally invasive bioprinting

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cheng Zhou ◽  
Youzhou Yang ◽  
Jiaxin Wang ◽  
Qingyang Wu ◽  
Zhuozhi Gu ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
The Body ◽  
Magnetic Actuation ◽  
Internal Organs ◽  
Planar Surfaces ◽  
Reinforced Polymer ◽  
Direct Fabrication ◽  
Digitally Controlled

AbstractIn vivo bioprinting has recently emerged as a direct fabrication technique to create artificial tissues and medical devices on target sites within the body, enabling advanced clinical strategies. However, existing in vivo bioprinting methods are often limited to applications near the skin or require open surgery for printing on internal organs. Here, we report a ferromagnetic soft catheter robot (FSCR) system capable of in situ computer-controlled bioprinting in a minimally invasive manner based on magnetic actuation. The FSCR is designed by dispersing ferromagnetic particles in a fiber-reinforced polymer matrix. This design results in stable ink extrusion and allows for printing various materials with different rheological properties and functionalities. A superimposed magnetic field drives the FSCR to achieve digitally controlled printing with high accuracy. We demonstrate printing multiple patterns on planar surfaces, and considering the non-planar surface of natural organs, we then develop an in situ printing strategy for curved surfaces and demonstrate minimally invasive in vivo bioprinting of hydrogels in a rat model. Our catheter robot will permit intelligent and minimally invasive bio-fabrication.

scholarly journals Analysis of the ex-vivo transformation of semen, saliva and urine as they dry out using ATR-FTIR spectroscopy and chemometric approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tanurup Das ◽  
Abhimanyu Harshey ◽  
Ankit Srivastava ◽  
Kriti Nigam ◽  
Vijay Kumar Yadav ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Ex Vivo ◽  
Body Fluids ◽  
Biochemical Changes ◽  
Partial Least Square ◽  
The Body ◽  
Slow Phase ◽  
Time Since Deposition ◽  
Dry Out

AbstractThe ex-vivo biochemical changes of different body fluids also referred as aging of fluids are potential marker for the estimation of Time since deposition. Infrared spectroscopy has great potential to reveal the biochemical changes in these fluids as previously reported by several researchers. The present study is focused to analyze the spectral changes in the ATR-FTIR spectra of three body fluids, commonly encountered in violent crimes i.e., semen, saliva, and urine as they dry out. The whole analytical timeline is divided into relatively slow phase I due to the major contribution of water and faster Phase II due to significant evaporation of water. Two spectral regions i.e., 3200–3400 cm−1 and 1600–1000 cm−1 are the major contributors to the spectra of these fluids. Several peaks in the spectral region between 1600 and 1000 cm−1 showed highly significant regression equation with a higher coefficient of determination values in Phase II in contrary to the slow passing Phase I. Principal component and Partial Least Square Regression analysis are the two chemometric tool used to estimate the time since deposition of the aforesaid fluids as they dry out. Additionally, this study potentially estimates the time since deposition of an offense from the aging of the body fluids at the early stages after its occurrence as well as works as the precursor for further studies on an extended timeframe.

scholarly journals Development of In Situ Gelling Meloxicam-Human Serum Albumin Nanoparticle Formulation for Nose-to-Brain Application

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 646
Author(s):  
Gábor Katona ◽  
Bence Sipos ◽  
Mária Budai-Szűcs ◽  
György Tibor Balogh ◽  
Szilvia Veszelka ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Nasal Mucosa ◽  
Drug Absorption ◽  
Cell Damage ◽  
Lipid Fraction ◽  
Poloxamer 407 ◽  
Nasal Drug Delivery

The aim of this study was to develop an intranasal in situ thermo-gelling meloxicam-human serum albumin (MEL-HSA) nanoparticulate formulation applying poloxamer 407 (P407), which can be administered in liquid state into the nostril, and to increase the resistance of the formulation against mucociliary clearance by sol-gel transition on the nasal mucosa, as well as to improve drug absorption. Nanoparticle characterization showed that formulations containing 12–15% w/w P407 met the requirements of intranasal administration. The Z-average (in the range of 180–304 nm), the narrow polydispersity index (PdI, from 0.193 to 0.328), the zeta potential (between −9.4 and −7.0 mV) and the hypotonic osmolality (200–278 mOsmol/L) of MEL-HSA nanoparticles predict enhanced drug absorption through the nasal mucosa. Based on the rheological, muco-adhesion, drug release and permeability studies, the 14% w/w P407 containing formulation (MEL-HSA-P14%) was considered as the optimized formulation, which allows enhanced permeability of MEL through blood–brain barrier-specific lipid fraction. Cell line studies showed no cell damage after 1-h treatment with MEL-HSA-P14% on RPMI 2650 human endothelial cells’ moreover, enhanced permeation (four-fold) of MEL from MEL-HSA-P14% was observed in comparison to pure MEL. Overall, MEL-HSA-P14% can be promising for overcoming the challenges of nasal drug delivery.

scholarly journals Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 54
Author(s):  
Christine Landlinger ◽  
Lenka Tisakova ◽  
Vera Oberbauer ◽  
Timo Schwebs ◽  
Abbas Muhammad ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Bactericidal Activity ◽  
High Selectivity ◽  
Ex Vivo ◽  
Vaginal Microbiome ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
Promising Alternative ◽  
First Time

Bacterial vaginosis is characterized by an imbalance of the vaginal microbiome and a characteristic biofilm formed on the vaginal epithelium, which is initiated and dominated by Gardnerella bacteria, and is frequently refractory to antibiotic treatment. We investigated endolysins of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages as an alternative treatment. When recombinantly expressed, these proteins demonstrated strong bactericidal activity against four different Gardnerella species. By domain shuffling, we generated several engineered endolysins with 10-fold higher bactericidal activity than any wild-type enzyme. When tested against a panel of 20 Gardnerella strains, the most active endolysin, called PM-477, showed minimum inhibitory concentrations of 0.13–8 µg/mL. PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. Furthermore, the efficacy of PM-477 was tested by fluorescence in situ hybridization on vaginal samples of fifteen patients with either first time or recurring bacterial vaginosis. In thirteen cases, PM-477 killed the Gardnerella bacteria and physically dissolved the biofilms without affecting the remaining vaginal microbiome. The high selectivity and effectiveness in eliminating Gardnerella, both in cultures of isolated strains as well as in clinically derived samples of natural polymicrobial biofilms, makes PM-477 a promising alternative to antibiotics for the treatment of bacterial vaginosis, especially in patients with frequent recurrence.

scholarly journals Dynamic Imaging of IEL-IEC Co-Cultures Allows for Quantification of CD103-Dependent T Cell Migration

2021 ◽  
Vol 22 (10) ◽  
pp. 5148
Author(s):  
Karin Enderle ◽  
Martin Dinkel ◽  
Eva-Maria Spath ◽  
Benjamin Schmid ◽  
Sebastian Zundler ◽  
...  
Keyword(s):  
T Cell ◽  
Cross Talk ◽  
Intestinal Inflammation ◽  
Ex Vivo ◽  
New Technology ◽  
Surface Expression ◽  
Intraepithelial Lymphocytes ◽  
Dynamic Imaging ◽  
The Body ◽  
Therapeutic Interventions

Intraepithelial lymphocytes (IEL) are widely distributed within the small intestinal epithelial cell (IEC) layer and represent one of the largest T cell pools of the body. While implicated in the pathogenesis of intestinal inflammation, detailed insight especially into the cellular cross-talk between IELs and IECs is largely missing in part due to lacking methodologies to monitor this interaction. To overcome this shortcoming, we employed and validated a murine IEL-IEC (organoids) ex vivo co-culture model system. Using livecell imaging we established a protocol to visualize and quantify the spatio-temporal migratory behavior of IELs within organoids over time. Applying this methodology, we found that IELs lacking CD103 (i.e., integrin alpha E, ITGAE) surface expression usually functioning as a retention receptor for IELs through binding to E-cadherin (CD324) expressing IECs displayed aberrant mobility and migration patterns. Specifically, CD103 deficiency affected the ability of IELs to migrate and reduced their speed during crawling within organoids. In summary, we report a new technology to monitor and quantitatively assess especially migratory characteristics of IELs communicating with IEC ex vivo. This approach is hence readily applicable to study the effects of targeted therapeutic interventions on IEL-IEC cross-talk.

scholarly journals Capsazepine decreases corneal pain syndrome in severe dry eye disease

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Darine Fakih ◽  
Adrian Guerrero-Moreno ◽  
Christophe Baudouin ◽  
Annabelle Réaux-Le Goazigo ◽  
Stéphane Mélik Parsadaniantz
Keyword(s):  
In Situ Hybridization ◽  
Inflammatory Pain ◽  
Transient Receptor Potential ◽  
Ex Vivo ◽  
Receptor Potential ◽  
Eye Disease ◽  
Ocular Pain ◽  
Trpv1 Antagonist ◽  
Transient Receptor

Abstract Background Dry eye disease (DED) is a multifactorial disease of the ocular surface accompanied by neurosensory abnormalities. Here, we evaluated the effectiveness of transient receptor potential vanilloid-1 (TRPV1) blockade to alleviate ocular pain, neuroinflammation, and anxiety-like behavior associated with severe DED. Methods Chronic DED was induced by unilateral excision of the Harderian and extraorbital lacrimal glands of adult male mice. Investigations were conducted at 21 days after surgery. The mRNA levels of TRPV1, transient receptor potential ankyrin-1 (TRPA1), and acid-sensing ion channels 1 and 3 (ASIC1 and ASIC3) in the trigeminal ganglion (TG) were evaluated by RNAscope in situ hybridization. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous and stimulated (cold, heat, and acid) corneal nerve responsiveness in ex vivo eye preparations. DED mice received topical instillations of the TRPV1 antagonist (capsazepine) twice a day for 2 weeks from d7 to d21 after surgery. The expression of genes involved in neuropathic and inflammatory pain was evaluated in the TG using a global genomic approach. Chemical and mechanical corneal nociception and spontaneous ocular pain were monitored. Finally, anxiety-like behaviors were assessed by elevated plus maze and black and white box tests. Results First, in situ hybridization showed DED to trigger upregulation of TRPV1, TRPA1, ASIC1, and ASIC3 mRNA in the ophthalmic branch of the TG. DED also induced overexpression of genes involved in neuropathic and inflammatory pain in the TG. Repeated instillations of capsazepine reduced corneal polymodal responsiveness to heat, cold, and acidic stimulation in ex vivo eye preparations. Consistent with these findings, chronic capsazepine instillation inhibited the upregulation of genes involved in neuropathic and inflammatory pain in the TG of DED animals and reduced the sensation of ocular pain, as well as anxiety-like behaviors associated with severe DED. Conclusion These data provide novel insights on the effectiveness of TRPV1 antagonist instillation in alleviating abnormal corneal neurosensory symptoms induced by severe DED, opening an avenue for the repositioning of this molecule as a potential analgesic treatment for patients suffering from chronic DED.

Sign in / Sign up

Export Citation Format

Share Document