Chitosan and its derivatives in 3D/4D (bio) printing for tissue engineering and drug delivery applications.

Tissue engineering research has undergone to a revolutionary improvement, thanks to technological advancements, such as the introduction of bioprinting technologies. The ability to develop suitable customized biomaterial inks/bioinks, with excellent printability and ability to promote cell proliferation and function, has a deep impact on such improvements. In this context, printing inks based on chitosan and its derivatives have been instrumental. Thus, the current review aims at providing a comprehensive overview on chitosan-based materials as suitable inks for 3D/4D (bio)printing and their applicability in creating advanced drug delivery platforms and tissue engineered constructs. Furthermore, relevant strategies to improve the mechanical and biological performances of this biomaterial are also highlighted.

Commercially Available Textiles as a Scaffolding Platform for Large-Scale Cell Culture.

The present study outlines the evaluation of textile materials that are currently in the market for cell culture applications. By using normal LaserJet printing techniques, we created the substrates, which were then characterized physicochemically and biologically. In particular, (i) we found that the weave pattern and (ii) the chemical nature of the textiles significantly influenced the behaviour of the cells. Textiles with closely knitted fibers and cell adhesion motifs, exhibited better cell adhesion and proliferation over a period of 7 days. All the substrates supported good viability of cells (>80%). We believe that these aspects make commercially available textiles as a potential candidate for large-scale culture of adherent cells.

Transition Metal Dichalcogenides (TMDC)-Based Nanozymes for Biosensing and Therapeutic Applications.

Nanozymes, a type of nanomaterial with enzyme-like properties, are a promising alternative to natural enzymes. In particular, transition metal dichalcogenides (TMDCs, with the general formula MX2, where M represents a transition metal and X is a chalcogen element)-based nanozymes have demonstrated exceptional potential in the healthcare and diagnostic sectors. TMDCs have different enzymatic properties due to their unique nano-architecture, high surface area, and semiconducting properties with tunable band gaps. Furthermore, the compatibility of TMDCs with various chemical or physical modification strategies provide a simple and scalable way to engineer and control their enzymatic activity. Here, we discuss recent advances made with TMDC-based nanozymes for biosensing and therapeutic applications. We also discuss their synthesis strategies, various enzymatic properties, current challenges, and the outlook for future developments in this field.

Mesoporous Bioactive Glasses in Cancer Diagnosis and Therapy: Stimuli-Responsive, Toxicity, Immunogenicity, and Clinical Translation.

Cancer is one of the top life-threatening dangers to the human survival, accounting for over 10 million deaths per year. Bioactive glasses have developed dramatically since their discovery 50 years ago, with applications that include therapeutics as well as diagnostics. A new system within the bioactive glass family, mesoporous bioactive glasses (MBGs), has evolved into a multifunctional platform, thanks to MBGs easy-to-functionalize nature and tailorable textural properties-surface area, pore size, and pore volume. Although MBGs have yet to meet their potential in tumor treatment and imaging in practice, recently research has shed light on the distinguished MBGs capabilities as promising theranostic systems for cancer imaging and therapy. This review presents research progress in the field of MBG applications in cancer diagnosis and therapy, including synthesis of MBGs, mechanistic overview of MBGs application in tumor diagnosis and drug monitoring, applications of MBGs in cancer therapy ( particularly, targeted delivery and stimuli-responsive nanoplatforms), and immunological profile of MBG-based nanodevices in reference to the development of novel cancer therapeutics.

4D printing in biomedical applications: emerging trends and technologies.

Nature's material systems during evolution have developed the ability to respond and adapt to environmental stimuli through the generation of complex structures capable of varying their functions across direction, distances and time. 3D printing technologies can recapitulate structural motifs present in natural materials, and efforts are currently being made on the technological side to improve printing resolution, shape fidelity, and printing speed. However, an intrinsic limitation of this technology is that printed objects are static and thus inadequate to dynamically reshape when subjected to external stimuli. In recent years, this issue has been addressed with the design and precise deployment of smart materials that can undergo a programmed morphing in response to a stimulus. The term 4D printing was coined to indicate the combined use of additive manufacturing, smart materials, and careful design of appropriate geometries. In this review, we report the recent progress in the design and development of smart materials that are actuated by different stimuli and their exploitation within additive manufacturing to produce biomimetic structures with important repercussions in different but interrelated biomedical areas.

Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights.

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.

Recent advances in bioprinting technologies for engineering cardiac tissue.

Annually increasing incidence of cardiac-related disorders and cardiac tissue's minimal regenerative capacity have motivated the researchers to explore effective therapeutic strategies. In the recent years, bioprinting technologies have witnessed a great wave of enthusiasm and have undergone steady advancements over a short period, opening the possibilities for recreating engineered functional cardiac tissue models for regenerative and diagnostic applications. With this perspective, the current review delineates recent developments in the sphere of engineered cardiac tissue fabrication, using traditional and advanced bioprinting strategies. The review also highlights different printing ink formulations, available cellular opportunities, and aspects of personalized medicines in the context of cardiac tissue engineering and bioprinting. On a concluding note, current challenges and prospects for further advancements are also discussed.

Recent advances in bioprinting technologies for engineering different cartilage-based tissues.

Inadequate self-repair and regenerative efficiency of the cartilage tissues has motivated the researchers to devise advanced and effective strategies to resolve this issue. Introduction of bioprinting to tissue engineering has paved the way for fabricating complex biomimetic engineered constructs. In this context, the current review gears off with the discussion of standard and advanced 3D/4D printing technologies and their implications for the repair of different cartilage tissues, namely, articular, meniscal, nasoseptal, auricular, costal, and tracheal cartilage. The review is then directed towards highlighting the current stem cell opportunities. On a concluding note, associated critical issues and prospects for future developments, particularly in this sphere of personalized medicines have been discussed.

Recent advances in bioprinting technologies for engineering hepatic tissue.

In the sphere of liver tissue engineering (LTE), 3D bioprinting has emerged as an effective technology to mimic the complex in vivo hepatic microenvironment, enabling the development of functional 3D constructs with potential application in the healthcare and diagnostic sector. This review gears off with a note on the liver's microscopic 3D architecture and pathologies linked to liver injury. The write-up is then directed towards unmasking recent advancements and prospects of bioprinting for recapitulating 3D hepatic structure and function. The article further introduces available stem cell opportunities and different strategies for their directed differentiation towards various hepatic stem cell types, including hepatocytes, hepatic sinusoidal endothelial cells, stellate cells, and Kupffer cells. Another thrust of the article is on understanding the dynamic interplay of different hepatic cells with various microenvironmental cues, which is crucial for controlling differentiation, maturation, and maintenance of functional hepatic cell phenotype. On a concluding note, various critical issues and future research direction towards clinical translation of bioprinted hepatic constructs are discussed.

Oxygen releasing materials: Towards addressing the hypoxia-related issues in tissue engineering.

Manufacturing macroscale cell-laden architectures is one of the biggest challenges faced nowadays in the domain of tissue engineering. Such living constructs, in fact, pose strict requirements for nutrients and oxygen supply that can hardly be addressed through simple diffusion in vitro or without a functional vasculature in vivo. In this context, in the last two decades, a substantial amount of work has been carried out to develop smart materials that could actively provide oxygen-release to contrast local hypoxia in large-size constructs. This review provides an overview of the currently available oxygen-releasing materials and their synthesis and mechanism of action, highlighting their capacities under in vitro tissue cultures and in vivo contexts. Additionally, we also showcase an emerging concept, herein termed as "living materials as releasing systems", which relies on the combination of biomaterials with photosynthetic microorganisms, namely algae, in an "unconventional" attempt to supply the damaged or re-growing tissue with the necessary supply of oxygen. We envision that future advances focusing on tissue microenvironment regulated oxygen-supplying materials would unlock an untapped potential for generating a repertoire of anatomic scale, living constructs with improved cell survival, guided differentiation, and tissue-specific biofunctionality.

Gum polysaccharide/nanometal hybrid biocomposites in cancer diagnosis and therapy.

Biopolymers are of prime importance among which gum polysaccharides hold an eminent standing owing to their high availability and non-toxic nature. Gum biopolymers offer a greener alternative to synthetic polymers and toxic chemicals in the synthesis of metal nanostructures. Metal nanostructures accessible via eco-friendly means endow astounding characteristics to gum-based biocomposites in the field of diagnosis and therapy towards cancer diseases. In this review, assorted approaches for the assembly of nanomaterials mediated by gum biopolymers are presented and their utility in cancer diagnosis and therapy, e.g., bioimaging, radiotherapy, and phototherapy, are deliberated to provide a groundwork for future stimulative research.

PBP4 and PBP5 are involved in regulating exopolysaccharide synthesis during Escherichia coli biofilm formation.

Escherichia coli low-molecular-mass (LMM) Penicillin-binding proteins (PBPs) help in hydrolysing the peptidoglycan fragments from their cell wall and recycling them back into the growing peptidoglycan matrix, in addition to their reported involvement in biofilm formation. Biofilms are external slime layers of extra-polymeric substances that sessile bacterial cells secrete to form a habitable niche for themselves. Here, we hypothesize the involvement of Escherichia coli LMM PBPs in regulating the nature of exopolysaccharides (EPS) prevailing in its extra-polymeric substances during biofilm formation. Therefore, this study includes the assessment of physiological characteristics of E. coli CS109 LMM PBP deletion mutants to address biofilm formation abilities, viability and surface adhesion. Finally, EPS from parent CS109 and its ΔPBP4 and ΔPBP5 mutants were purified and analysed for sugars present. Deletions of LMM PBP reduced biofilm formation, bacterial adhesion and their viability in biofilms. Deletions also diminished EPS production by ΔPBP4 and ΔPBP5 mutants, purification of which suggested an increased overall negative charge compared with their parent. Also, EPS analyses from both mutants revealed the appearance of an unusual sugar, xylose, that was absent in CS109. Accordingly, the reason for reduced biofilm formation in LMM PBP mutants may be speculated as the subsequent production of xylitol and a hindrance in the standard flow of the pentose phosphate pathway.

A review on advances in graphene-derivative/polysaccharide bionanocomposites: Therapeutics, pharmacogenomics and toxicity.

Graphene-based bionanocomposites are employed in several ailments, such as cancers and infectious diseases, due to their large surface area (to carry drugs), photothermal properties, and ease of their functionalization (owing to their active groups). Modification of graphene-derivatives with polysaccharides is a promising strategy to decrease their toxicity and improve target ability, which consequently enhances their biotherapeutic efficacy. Herein, functionalization of graphene-based materials with carbohydrate polymers (e.g., chitosan, starch, alginate, hyaluronic acid, and cellulose) are presented. Subsequently, recent advances in graphene nanomaterial/polysaccharide-based bionanocomposites in infection treatment and cancer therapy are comprehensively discussed. Pharmacogenomic and toxicity assessments for these bionanocomposites are also highlighted to provide insight for future optimized and smart investigations and researches.

Synthesis and characterization of PCL-DA:PEG-DA based polymeric blends grafted with SMA hydrogel as bio-degradable intrauterine contraceptive implant.

Presently available long-acting reversible female contraceptive implants are said to be an effective way of preventing unintended pregnancy. Unacceptable side effects attributed by these contraceptive implants act as a major drawback for the practitioners. These problems pave the way for the development of a new form of long-acting non-hormonal female contraceptive implant, especially in the developing countries. PCL-DA: PEG-DA polymeric scaffold is grafted with Styrene Maleic Anhydride (SMA) based hydrogel, and their physicochemical, thermal and biological parameters are being explored for developing a bio-degradable form of the non-hormonal intrauterine contraceptive implant. With the fixed ratio of PEG-DA: PCL-DA polymer, SMA hydrogel was added at four different concentrations to determine the optimum concentration of SMA hydrogel for the development of a promising long-acting biodegradable intrauterine contraceptive implant. Structural elucidation of the polymers was confirmed using 1H and 13C NMR spectroscopic analyses. The physiochemical characterization report suggests that SMA hydrogel interacts with the PCL-DA: PEG-DA polymeric scaffold through intermolecular hydrogen bonding interaction. The in-vitro spermicidal activity of the polymeric scaffold increases when the concentration of SMA based hydrogel in the polymer samples is increased without showing any significant toxicological effects. From the study results, it may be concluded that SMA hydrogel grafted PCL-DA: PEG-DA scaffold can be developed as intra-uterine biodegradable non-hormonal female contraceptive implant due to its excellent bio-compatibility and spermicidal activity.

Nanotailored hyaluronic acid modified methylcellulose as an injectable scaffold with enhanced physico-rheological and biological aspects.

The collaborative endeavor in tissue engineering is to fabricate a bio-mimetic extracellular matrix to assist tissue regeneration. Thus, a novel injectable tissue scaffold was fabricated by exploring nanotailored hyaluronic acid (nHA) and methylcellulose (MC) (nHAMC) along with pristine HA based MC scaffold (HAMC). nHA with particle size ∼22 ±â€¯5.3 nm were obtained and nHAMC displayed a honeycomb-like 3D microporous architecture. Nano-HA bestowed better gel strength, physico-rheological and biological properties than HA. It creditably reduced the high content of salt to reduce the gelation temperature of MC. The properties ameliorated with increased in-corporation of nano-HA. The addition of salt showed more prominent effect on gelation temperature of nHAMC than in HAMC; and salting-out effect was dependent on nHA/HA content. Biocompatible nHAMC assisted adequate cell adherence and proliferation with more extended protrusions with better migration rate than control. Thus, biomodulatory effect of nanotailored glycosaminoglycan could be asserted to design an efficient thermo-responsive scaffold.

Fractal self-assembly and aggregation of human amylin.

Human amylin is an intrinsically disordered protein believed to have a central role in Type-II diabetes mellitus (T2DM). The formation of intermediate oligomers is a seminal event in the eventual self-assembled fibril structures of amylin. However, the recent experimental investigations have shown the presence of different self-assembled (oligomers, protofilaments, and fibrils) and aggregated structures (amorphous aggregates) of amylin formed during its aggregation. Here, we show that amylin under diffusion-limited conditions leads to fractal self-assembly. The pH and solvent sensitive fractal self-assemblies of amylin were observed using an optical microscope. Confocal microscopy and scanning electron microscopy (SEM) with energy dispersion X-ray analysis (EDAX) were used to confirm the fractal self-assembly of amylin in water and PBS buffer, respectively. The fractal characteristics of the self-assemblies and the aggregates formed during the aggregation of amylin under different pH conditions were investigated using laser light scattering. The hydropathy and the docking study indicated the interactions between the anisotropically distributed hydrophobic residues and polar/ionic residues on the solvent-accessible surface of the protein as the crucial interaction hot-spots for driving the self-assembly and aggregation of human amylin. The simultaneous presence of various self-assemblies of human amylin was observed through different microscopy techniques. The present study may help in designing different fractal-like nanomaterials with potential applications in drug delivery, sensing, and tissue engineering.

Selective Self-Assembly of 5-Fluorouracil through Nonlinear Solvent Response Modulates Membrane Dynamics.

Controllable self-assembly and understanding of the interaction between single metabolite fibrils and live-cell membranes have paramount importance in providing minimal treatment in several neurodegenerative disorders. Here, utilizing the nonlinear nature and peculiar hydrogen bonding behavior of the dimethyl sulfoxide (DMSO)-water mixture, the selective self-assembly of a single metabolite 5-fluorouracil (5-FU) is achieved. A direct correlation between water availability and selective self-assembly of 5-FU is ratified from the excited-state dynamics. The specific fibrillar structures of 5-FU exhibit a great potential to modulate live cell membrane fluidity and model membrane lipid distribution. After 5-FU fibril addition, a disorder of H-bonded water molecules arises several layers beyond the first hydration shell of the polar headgroups, which essentially modifies interfacial water structure and dynamics. Overall, our results shed light on the role of solvent to govern specific self-assembly and also lay the foundation accounting for the earlier stage of several diseases and multidrug resistance.

Quinoline H2S donor decorated fluorescent carbon dots: visible light responsive H2S nanocarriers.

Recent studies have shown that the utility of nanocarriers for the transportation of gaseous signalling molecules to their target site in a biological environment is an effective approach. In this work, we have developed for the first time visible light responsive nanocarriers for the effective release of H2S. Our newly developed nanocarriers for H2S release are constructed using two main ingredients: fluorescent carbon dots and quinoline as an H2S donor. The developed nanocarriers provided interesting properties like good solubility under physiological conditions, excellent fluorescence properties and efficient release ability of H2S with good quantum yield upon visible light irradiation. In vitro studies revealed that our designed nanocarriers exhibited abilities like efficient cellular internalization and good biocompatibility.

Inexpensive and Versatile Paper-Based Platform for 3D Culture of Liver Cells and Related Bioassays.

The present study delineates the fabrication of paper-based devices for culturing liver cells and developing related bioassays. The devices were prepared by conventional lab-based LaserJet printing technology and employed for 3D cell culture. Our results demonstrated that the devices efficiently supported the growth of multiple cell types incuding HepG2, HUVEC, fibroblasts, and MSCs. We further showed that the device specifications (grade of paper or design parameters) greatly impacted the functional phenotype of the HepG2 cells. We also explored the application of the developed devices for routine cell culture, drug screening, coculture, and transwell migration assays. The cellular responses observed on the paper under different culture configurations were similar to those obtained in the case of tissue culture plate (TCP). Moreover, we showed that the paper-based devices were compatible with the immunocytochemistry and ELISA procedures (no indication of nonspecific matrix-antibody interaction). Considering the simplicity, experimental flexibility, cost-effectiveness, and multiplexibility of the paper-based liver models, it is deemed to be ideal for developing cell-based bioassays, especially in resource-limited settings.