3D Bioprinting of Human Hollow Organs.

3D bioprinting is a rapidly evolving technique that has been found to have extensive applications in disease research, tissue engineering, and regenerative medicine. 3D bioprinting might be a solution to global organ shortages and the growing aversion to testing cell patterning for novel tissue fabrication and building superior disease models. It has the unrivaled capability of layer-by-layer deposition using different types of biomaterials, stem cells, and biomolecules with a perfectly regulated spatial distribution. The tissue regeneration of hollow organs has always been a challenge for medical science because of the complexities of their cell structures. In this mini review, we will address the status of the science behind tissue engineering and 3D bioprinting of epithelialized tubular hollow organs. This review will also cover the current challenges and prospects, as well as the application of these complicated 3D-printed organs.

Synthesis and characterization of ester-diol based polyurethane: a potentiality check for hypopharyngeal tissue engineering application.

ABSTRACT: Hypopharyngeal tissue engineering is increasing rapidly in this developing world. Tissue damage or loss needs the replacement by another biological or synthesized membrane using tissue engineering. Tissue engineering research is emerging to provide an effective solution for damaged tissue replacement. Polyurethane in tissue engineering has successfully been used to repair and restore the function of damaged tissues. In this context, Can polyurethane be a useful material to deal with hypopharyngeal tissue defects? To explore this, here ester diol based polyurethane (PU) was synthesized in two steps: firstly, polyethylene glycol 400 (PEG 400) was reacted with lactic acid to prepare ester diol, and then it was polymerized with hexamethylene diisocyanate. The physical, mechanical, and biological testing was done to testify the characterization of the membrane. The morphology of the synthesized membrane was investigated by using field emission scanning electron microscopy. Functional groups of the obtained membrane were characterized by fourier transform infrared spectroscopy spectroscopy. Several tests were performed to check the in vitro and in vivo biocompatibility of the membrane. A highly connected homogeneous network was obtained due to the appropriate orientation of a hard segment and soft segment in the synthesized membrane. Mechanical property analysis indicates the membrane has a strength of 5.15 MPa and strain 124%. The membrane showed high hemocompatibility, no cytotoxicity on peripheral blood mononuclear cell, and susceptible to degradation in simulated body fluid solution. Antimicrobial activity assessment has shown promising results against clinically significant bacteria. Primary hypopharyngeal cell growth on the PU membrane revealed the cytocompatibility and subcutaneous implantation on the back of Wistar rats were given in vivo biocompatibility of the membrane. Therefore, the synthesized material can be considered as a potential candidate for a hypopharyngeal tissue engineering application.

A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection.

Disseminated infection by Candida species represents a common, often life-threatening condition. Increased resistance to current antifungal drugs has led to an urgent need to develop new antifungal drugs to treat this pathogen. However, in vivo screening of candidate antifungal compounds requires large numbers of animals and using immunosuppressive agents to allow for fungal dissemination. To increase the efficiency of screening, to use fewer mice, and to remove the need for immunosuppressive agents, which may interfere with the drug candidates, we tested the potential for a novel approach using in vivo imaging of a fluorescent strain of Candida albicans, in a mouse strain deficient in the host defense peptide, murine ß-defensin 1 (mBD-1). We developed a strain of C. albicans that expresses red fluorescent protein (RFP), which exhibits similar infectivity to the non-fluorescent parent strain. When this strain was injected into immunocompetent mBD-1-deficient mice, we observed a non-lethal disseminated infection. Further, we could quantify its dissemination in real time, and observe the activity of an antifungal peptide mimetic drug by in vivo imaging. This novel method will allow for the rapid in vivo screening of antifungal drugs, using fewer mice, and increase the efficiency of testing new antifungal agents.

Potentials of polymeric nanoparticle as drug carrier for cancer therapy: with a special reference to pharmacokinetic parameters.

Nanomaterials have made a significant impact on cancer therapeutics and an emergence of polymeric nanoparticle provides a unique platform for delivery of drug molecules of diverse nature. Nanoparticles can be targeted at the tumor cells due to enhanced permeability and retention effect. Moreover, nanoparticles can be grafted by various ligands on their surface to target the specific receptors overexpressed by cancer cells or angiogenic endothelial cells. These approaches ultimately result in longer circulation half-lives, improved drug pharmacokinetics, reduced side effects of therapeutically active substances and overcoming cancer chemo-resistance thereby enhancing the therapeutic efficacy of the treatment. This review article summarizes the recent efforts in cancer nanochemotherapeutics using polymeric nanoparticles with a special reference to their pharmacokinetic and biodistribution profiles, their role in reversing multidrug resistance in cancer and strategies of tumor targeting with them, along with the challenges in the field.

Antisense oligonucleotides directed against insulin-like growth factor-II messenger ribonucleic acids delay the progress of rat hepatocarcinogenesis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a multistep complex process, caused by many of genetic alteration. Insulin-like growth factors and their receptor have been widely implicated to HCC. Insulin-like growth factor-II (IGF-II) is a mitogenic polypeptide, found in various fetal and neonatal tissues of humans and rats and expresses in HCC. Here we investigated anticancer potential of phosphorothioate antisense oligonucleotides (ASOs) against three coding exons (exon-1/exon-2/exon-3) of IGF-II messenger ribonucleic acid in rat hepatocarcinogenesis model. MATERIALS AND METHODS: During diethylnitrosamine and 2-acetylaminofluorene induced hepatocarcinogenesis, rats were treated with ASOs. Various biochemical and histological studies were conducted. RESULTS: About 40% of carcinogen treated rats, which received two oligomers (against exon-1 or-3) did not show any hepatic lesion, hyperplastic nodule or tumor and remaining 60% of those rats showed lesion incidence and had about 59% and 55% reductions in the numbers of hepatic altered foci, respectively. Reductions in the total lesion-area when compared with carcinogen control rats were 64% and 53%, respectively for the animals treated with carcinogen and received the ASOs against exon-1/-3. Fluorescein isothiocyanate-labeled ASO reached in the hepatocytes in 2 h. No predominant IGF-II overexpression was observed in case of rats treated with the two ASOs. Treatment of the antisense IGF-II oligomers in carcinogen treated rats show better hepatocellular integrity along with several preneoplastic/neoplastic marker isoenzyme/enzyme modulations. CONCLUSIONS: Two of the three antisense oligomer-types effectively controlled IGF-II overexpression, causing the delay of the development and/or progress of hepatic cancer in rats.

Colloidal gold-loaded, biodegradable, polymer-based stavudine nanoparticle uptake by macrophages: an in vitro study.

OBJECTIVE: We describe the development, evaluation, and comparison of colloidal gold-loaded, poly(d,l-lactic-co-glycolic acid)-based nanoparticles containing anti-acquired immunodeficiency syndrome drug stavudine and uptake of these nanoparticles by macrophages in vitro. METHODS: WE USED THE FOLLOWING METHODS IN THIS STUDY: drug-excipient interaction by Fourier transform infrared spectroscopy, morphology of nanoparticles by field-emission scanning electron microscopy, particle size by a particle size analyzer, and zeta potential and polydispersity index by a zetasizer. Drug loading and in vitro release were evaluated for formulations. The best formulation was incorporated with fluorescein isothiocyanate. Macrophage uptake of fluorescein isothiocyanate nanoparticles was studied in vitro. RESULTS: Variations in process parameters, such as speed of homogenization and amount of excipients, affected drug loading and the polydispersity index. We found that the drug was released for a prolonged period (over 63 days) from the nanoparticles, and observed cellular uptake of stavudine nanoparticles by macrophages. CONCLUSION: Experimental nanoparticles represent an interesting carrier system for the transport of stavudine to macrophages, providing reduced required drug dose and improved drug delivery to macrophages over an extended period. The presence of colloidal gold in the particles decreased the drug content and resulted in comparatively faster drug release.