Multi-Organs-on-Chips for Testing Small-Molecule Drugs: Challenges and Perspectives.

Organ-on-a-chip technology has been used in testing small-molecule drugs for screening potential therapeutics and regulatory protocols. The technology is expected to boost the development of novel therapies and accelerate the discovery of drug combinations in the coming years. This has led to the development of multi-organ-on-a-chip (MOC) for recapitulating various organs involved in the drug-body interactions. In this review, we discuss the current MOCs used in screening small-molecule drugs and then focus on the dynamic process of drug absorption, distribution, metabolism, and excretion. We also address appropriate materials used for MOCs at low cost and scale-up capacity suitable for high-performance analysis of drugs and commercial high-throughput screening platforms

Chitosan-hybrid poss nanocomposites for bone regeneration: The effect of poss nanocage on surface, morphology, structure and in vitro bioactivity

WOS: 000510955500064PubMed: 31622724POSS, regarded as the smallest silica particle, is widely used as nanofiller in polymer systems. POSS-based nanocomposites are deduced as novel materials having potency for biomedical applications owing to the enhanced biocompatibility and physicochemical characteristics. The aim of this work was to integrate the beneficial features of chitosan (CS) and OctaTMA-POSS nanoparticle to design nanocomposite for bone tissue regeneration. The nanocomposite scaffolds were fabricated by freeze-drying. The effects of POSS incorporation on morphology and structure of CS matrix were examined. Bioactivity and osteogenic effects of the POSS nanoparticles were investigated with cytocompatibility, cell proliferation, alkaline phosphatase activity, osteocalcin production and biomineralization assays. PUSS incorporation altered the surface morphology by increasing surface roughness. Nanocomposite scaffolds with 82-90% porosity exhibited an increase in compression modulus of scaffolds (78-107 kPa) compared to control CS group (56 kPa). Results indicated that CS-POSS scaffolds were found cytocompatible with 3T3, MG-63 and Saos-2 cell lines. POSS incorporation showed promising effects on osteoblast adhesion and proliferation as well as increasing ALP activity, octeocalcin secretion and biomineralization of cells. (C) 2019 Elsevier B.V. All rights reserved

Bioactive fish scale incorporated chitosan biocomposite scaffolds for bone tissue engineering

Recently, biologically active natural macromolecules have come into prominence to be used as potential materials in scaffold design due to their unique characteristics which can mimic the human tissue structure with their physical and chemical similarity. Among them, fish scale (FS) is a biologically active material with its structural similarity to bone tissue due to including type I collagen and hydroxyapatite and also have distinctive collagen arrangement. In the present study, it is aimed to design a novel composite scaffold with FS incorporation into chitosan (CH) matrix for bone tissue regeneration. Therefore, two biological macromolecules, fish scale and chitosan, were combined to produce bio-composite scaffold. First, FS were decellularized with the chemical method and disrupted physically as microparticles (100 in), followed by dispersal in CH with ultrasonic homogenisation, CH/FS scaffolds were fabricated by lyophilization technique. Scaffolds were characterized physically, chemically, mechanically, and morphologically. SEM and porosity results showed that CH/FS scaffolds have uniform pore structure showing high porosity. Mechanical properties and degradation rate are enhanced with increasing FS content. In vitro cytotoxicity, proliferation and osteogenic activity of the scaffolds were evaluated with SaOS-2 cell line. CH/FS scaffolds did not show any cytotoxicity effect and the cells were gradually proliferated during culture period. Cell viability results showed that, FS microparticles had a proliferative effect on SaOS-2 cells when compared to control group. ALP activity and biomineralization studies indicated that FS micro particle reinforcement increased osteogenic activity during culture period. As a biological macromolecule with unique characteristics, FS was found as cytocompatible and provided promising effects as reinforcement agents for polymeric scaffolds. In conclusion, fabricated CH/FS bio-composites showed potential for bone tissue engineering applications. (C) 2019 Elsevier B.V. All rights reserved

Engineered Liposomes in Interventional Theranostics of Solid Tumors

Funding Information: R.P. thanks the director of IIT-BHU, Varanasi, U.P., for encouraging and providing the necessary facility and support and would also like to thank the school of biochemical engineering, IIT-BHU. N.K. would like to thank CBR, Population Council, for providing the Sheldon J. Segal Post-Doctoral Fellowship. P.C. acknowledges the support from the DST-funded I-DAPT Hub Foundation, IIT BHU [DST/NMICPS/TIH11/IIT(BHU)2020/02]. The authors thank Leander Corrie, Arun Butreddy, Sachin Kumar, and Qing He for reading this manuscript. J.C. acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). The author dedicates this article to Prof. Sanjiv Sam Gambhir, a molecular imaging scientist. All reproduced images and figures have been cited in this review. Publisher Copyright: © 2023 American Chemical Society.Engineered liposomal nanoparticles have unique characteristics as cargo carriers in cancer care and therapeutics. Liposomal theranostics have shown significant progress in preclinical and clinical cancer models in the past few years. Liposomal hybrid systems have not only been approved by the FDA but have also reached the market level. Nanosized liposomes are clinically proven systems for delivering multiple therapeutic as well as imaging agents to the target sites in (i) cancer theranostics of solid tumors, (ii) image-guided therapeutics, and (iii) combination therapeutic applications. The choice of diagnostics and therapeutics can intervene in the theranostics property of the engineered system. However, integrating imaging and therapeutics probes within lipid self-assembly “liposome” may compromise their overall theranostics performance. On the other hand, liposomal systems suffer from their fragile nature, site-selective tumor targeting, specific biodistribution and premature leakage of loaded cargo molecules before reaching the target site. Various engineering approaches, viz., grafting, conjugation, encapsulations, etc., have been investigated to overcome the aforementioned issues. It has been studied that surface-engineered liposomes demonstrate better tumor selectivity and improved therapeutic activity and retention in cells/or solid tumors. It should be noted that several other parameters like reproducibility, stability, smooth circulation, toxicity of vital organs, patient compliance, etc. must be addressed before using liposomal theranostics agents in solid tumors or clinical models. Herein, we have reviewed the importance and challenges of liposomal medicines in targeted cancer theranostics with their preclinical and clinical progress and a translational overview.publishersversionepub_ahead_of_prin

In vitro evaluation of Spirulina platensis extract incorporated skin cream with its wound healing and antioxidant activities

Context: Algae have gained importance in cosmeceutical product development due to their beneficial effects on skin health and therapeutical value with bioactive compounds. Spirulina platensis Parachas (Phormidiaceae) is renowned as a potential source of high-value chemicals and recently used in skincare products. Objective: This study develops and evaluates skin creams incorporated with bioactive S. platensis extract. Materials and methods: Spirulina platensis was cultivated, the aqueous crude extract was prepared and in vitro cytotoxicity of S. platensis extract in the range of 0.001–1% concentrations for 1, 3 and 7 d on HS2 keratinocyte cells was determined. Crude extracts were incorporated in skin cream formulation at 0.01% (w/w) concentration and in vitro wound healing and genotoxicity studies were performed. Immunohistochemical staining was performed to determine the collagen activity. Results: 0.1% S. platensis extract exhibited higher proliferation activity compared with the control group with 198% of cell viability after 3 d. Skin cream including 1.125% S. platensis crude extract showed enhanced wound healing effect on HS2 keratinocyte cell line and the highest HS2 cell viability % was obtained with this concentration. The micronucleus (MN) assay results indicated that S. platensis extract incorporated creams had no genotoxic effect on human peripheral blood cells. Immunohistochemical analysis showed that collagen 1 immunoreactivity was improved by increased extract concentration and it was strongly positive in cells treated with 1.125% extract incorporated skin cream. Conclusions: The cell viability, wound healing activity and genotoxicity results showed that S. platensis incorporated skin cream could be of potential value in cosmeceutical and biomedical applications

Production and Characterization of a Novel Bilayer Nanocomposite Scaffold Composed of Chitosan/Si-nHap and Zein/POSS Structures for Osteochondral Tissue Regeneration

Osteochondral tissue is hard to regenerate after injuries or degenerative diseases. Traditional treatments still have disadvantages, such as donor tissue availability, donor site morbidity, implant loss, and limited durability of prosthetics. Thus, recent studies have focused on tissue engineering strategies to regenerate osteochondral defects with different scaffold designs. Scaffolds have been developed from monolayer structures to bilayer scaffolds to repair the cartilage-bone interface and to support each tissue separately. In this study, Si-substituted nano-hydroxyapatite particles (Si-nHap) and silica-based POSS nanocages were used as reinforcements in different polymer layers to mimic a cartilage-bone tissue interface. Chitosan and zein, which are widely used biopolymers, are used as polymer layers to mimic the structure. This study reports the development of a bilayer scaffold produced via fabrication of two different nanocomposite layers with different polymer-inorganic composites in order to satisfy the complex and diverse regenerative requirements of osteochondral tissue. The chitosan/Si-nHap microporous layer and the zein/POSS nanofiber layer were designed to mimic a bone-cartilage tissue interface. Bilayer scaffolds were characterized with SEM, compression, swelling, and biodegradation tests to determine morphological, physical, and mechanical properties. The results showed that the bilayer scaffold had a structure composed of microporous and nanofiber layers joined at a continuous interface with appropriate mechanical properties. Furthermore, in vitro cell culture studies have been performed with LDH, proliferation, fluorescence imaging, and ALP activity assays using osteosarcoma and chondrosarcoma cell lines. ALP expression levels provide a good illustration of the improved osteogenic potential of a porous chitosan/Si-nHap layer due to the Si-doped nHap incorporation. Histological data showed that both fiber and porous layers that mimic the cartilage and bone sections exhibit homogeneous cell distribution and matrix formation. Histochemical staining was used to determine the cell proliferation and ECM formation on each layer. In vitro studies indicated that zein-POSS/chitosan/Si-nHap nanocomposite bilayer scaffolds showed promising results for osteochondral regeneration

Bioactive snail mucus-slime extract loaded chitosan scaffolds for hard tissue regeneration: the effect of mucoadhesive and antibacterial extracts on physical characteristics and bioactivity of chitosan matrix

Biobased extracts comprise various bioactive components and they are widely used in tissue engineering applications to increase bioactivity as well as physical characteristics of biomaterials. Among animal sources, garden snail Helix aspersa has come into prominence with its antibacterial and regenerative extracts and show potential in tissue regeneration. Thus, in this study, bioactive H. aspersa extracts (slime, mucus) were loaded in chitosan (CHI) matrix to fabricate porous scaffolds for hard tissue regeneration. Physical, chemical properties, antimicrobial activity was determined as well as in vitro bioactivity for bone and cartilage regeneration. Mucus and slime incorporation enhanced mechanical properties and biodegradation rate of CHI matrix. Scanning electron microscopy images showed that the average pore size of the scaffolds decreased with higher extract content. Mucus and slime extracts showed antimicrobial effect on two bacterial strains. In vitro cytotoxicity, osteogenic and chondrogenic activity of the scaffolds were evaluated with Saos-2 and SW1353 cell lines in terms of Alkaline phosphatase activity, biomineralization, GAG, COMP and hydroxyproline content. Cell viability results showed that extracts had a proliferative effect on Saos-2 and SW1353 cells when compared to the control group. Mucus and slime extract loading increased osteogenic and chondrogenic activity. Thus, the bioactive extract loaded CHI scaffolds showed potential for bone and cartilage regeneration with enhanced physical properties and in vitro bioactivity