Biomaterial engineering for cell transplantation.

The current paradigm of medicine is mostly designed to block or prevent pathological events. Once the disease-led tissue damage occurs, the limited endogenous regeneration may lead to depletion or loss of function for cells in the tissues. Cell therapy is rapidly evolving and influencing the field of medicine, where in some instances attempts to address cell loss in the body. Due to their biological function, engineerability, and their responsiveness to stimuli, cells are ideal candidates for therapeutic applications in many cases. Such promise is yet to be fully obtained as delivery of cells that functionally integrate with the desired tissues upon transplantation is still a topic of scientific research and development. Main known impediments for cell therapy include mechanical insults, cell viability, host's immune response, and lack of required nutrients for the transplanted cells. These challenges could be divided into three different steps: 1) Prior to, 2) during the and 3) after the transplantation procedure. In this review, we attempt to briefly summarize published approaches employing biomaterials to mitigate the above technical challenges. Biomaterials are offering an engineerable platform that could be tuned for different classes of cell transplantation to potentially enhance and lengthen the pharmacodynamics of cell therapies.

How to Sample Dozens of Substitutions per Site with λ Dynamics.

Alchemical free energy methods are useful in computer-aided drug design and computational protein design because they provide rigorous statistical mechanics-based estimates of free energy differences from molecular dynamics simulations. λ dynamics is a free energy method with the ability to characterize combinatorial chemical spaces spanning thousands of related systems within a single simulation, which gives it a distinct advantage over other alchemical free energy methods that are mostly limited to pairwise comparisons. Recently developed methods have improved the scalability of λ dynamics to perturbations at many sites; however, the size of chemical space that can be explored at each individual site has previously been limited to fewer than ten substituents. As the number of substituents increases, the volume of alchemical space corresponding to nonphysical alchemical intermediates grows exponentially relative to the size corresponding to the physical states of interest. Beyond nine substituents, λ dynamics simulations become lost in an alchemical morass of intermediate states. In this work, we introduce new biasing potentials that circumvent excessive sampling of intermediate states by favoring sampling of physical end points relative to alchemical intermediates. Additionally, we present a more scalable adaptive landscape flattening algorithm for these larger alchemical spaces. Finally, we show that this potential enables more efficient sampling in both protein and drug design test systems with up to 24 substituents per site, enabling, for the first time, simultaneous simulation of all 20 amino acids.

Cell Encapsulation and 3D Bioprinting for Therapeutic Cell Transplantation.

The promise of cell therapy has been augmented by introducing biomaterials, where intricate scaffold shapes are fabricated to accommodate the cells within. In this review, we first discuss cell encapsulation and the promising potential of biomaterials to overcome challenges associated with cell therapy, particularly cellular function and longevity. More specifically, cell therapies in the context of autoimmune disorders, neurodegenerative diseases, and cancer are reviewed from the perspectives of preclinical findings as well as available clinical data. Next, techniques to fabricate cell-biomaterials constructs, focusing on emerging 3D bioprinting technologies, will be reviewed. 3D bioprinting is an advancing field that enables fabricating complex, interconnected, and consistent cell-based constructs capable of scaling up highly reproducible cell-biomaterials platforms with high precision. It is expected that 3D bioprinting devices will expand and become more precise, scalable, and appropriate for clinical manufacturing. Rather than one printer fits all, seeing more application-specific printer types, such as a bioprinter for bone tissue fabrication, which would be different from a bioprinter for skin tissue fabrication, is anticipated in the future.

A novel pH-responsive nanoniosomal emulsion for sustained release of curcumin from a chitosan-based nanocarrier: Emphasis on the concurrent improvement of loading, sustained release, and apoptosis induction.

Curcumin application as an anti-cancer drug is faced with several impediments. This study has developed a platform that facilitates the sustained release of curcumin, improves loading efficiency, and anti-cancer activity. Montmorillonite (MMT) nanoparticles were added to chitosan (CS)-agarose (Aga) hydrogel and then loaded with curcumin (Cur) to prepare a curcumin-loaded nanocomposite hydrogel. The loading capacity increased from 63% to 76% by adding MMT nanoparticles to a chitosan-agarose hydrogel. Loading the fabricated nanocomposite in the nanoniosomal emulsion resulted in sustained release of curcumin under acidic conditions. Release kinetics analysis showed diffusion and erosion are the dominant release mechanisms, indicating non-fickian (or anomalous) transport based on the Korsmeyer-Peppas model. FTIR spectra confirmed that all nanocomposite components were present in the fabricated nanocomposite. Besides, XRD results corroborated the amorphous structure of the prepared nanocomposite. Zeta potential results corroborated the stability of the fabricated nanocarrier. Cytotoxicity of the prepared CS-Aga-MMT-Cur on MCF-7 cells was comparable with that of curcumin-treated cells (p < 0.001). Moreover, the percentage of apoptotic cells increased due to the enhanced release profile resulting from the addition of MMT to the hydrogel and the incorporation of the fabricated nanocomposite into the nanoniosomal emulsion. To recapitulate, the current delivery platform improved loading, sustained release, and curcumin anti-cancer effect. Hence, this platform could be a potential candidate to mitigate cancer therapy restrictions with curcumin.

Two-Dimensional Graphitic Carbon Nitride (g-C3N4) Nanosheets and Their Derivatives for Diagnosis and Detection Applications.

The early diagnosis of certain fatal diseases is vital for preventing severe consequences and contributes to a more effective treatment. Despite numerous conventional methods to realize this goal, employing nanobiosensors is a novel approach that provides a fast and precise detection. Recently, nanomaterials have been widely applied as biosensors with distinctive features. Graphite phase carbon nitride (g-C3N4) is a two-dimensional (2D) carbon-based nanostructure that has received attention in biosensing. Biocompatibility, biodegradability, semiconductivity, high photoluminescence yield, low-cost synthesis, easy production process, antimicrobial activity, and high stability are prominent properties that have rendered g-C3N4 a promising candidate to be used in electrochemical, optical, and other kinds of biosensors. This review presents the g-C3N4 unique features, synthesis methods, and g-C3N4-based nanomaterials. In addition, recent relevant studies on using g-C3N4 in biosensors in regard to improving treatment pathways are reviewed.

Ameliorating quercetin constraints in cancer therapy with pH-responsive agarose-polyvinylpyrrolidone -hydroxyapatite nanocomposite encapsulated in double nanoemulsion.

Despite quercetin (QC) promising features for cancer therapy, low solubility, poor permeability, and short biological half-life time significantly confine its application in cancer therapy. In this study, a novel approach is developed to improve loading efficiency and attain quercetin sustained-release concurrently. In this direction, hydrogel nanocomposite of agarose (AG)-polyvinylpyrrolidone (PVP)-hydroxyapatite (HAp) was loaded with QC. Incorporating HAp nanoparticles in the AG-PVP hydrogel improved the loading efficiency up to 61%. Also, the interactions between nanoparticle, drug, and hydrogel polymers rendered the nanocomposite pH-responsive at acidic conditions and controlled the burst release at neutral conditions. Then, QC-loaded hydrogel was encapsulated into the water in oil in water nanoemulsions to further sustain the drug release. As a result, the pH-responsive release of QC with prolonged-release over 96 h was observed. In more detail, according to the Korsmeyer-Peppas mathematical model, the mechanism of release was anomalous (diffusion-controlled) at pH 7.4 and anomalous transport (dissolution-controlled) at pH 5.4. The presence of all nanocomposite components was confirmed with FTIR analysis, and XRD results approved the incorporation of QC in the fabricated nanocomposite. The homogeneous surface of the nanocomposite in FESEM images showed good compatibility between components. The zeta potential analysis confirmed the good stability of the nanocarriers. Besides, the fabricated AG-PVP-HAp-QC platform showed significant cytotoxicity on MCF-7 cells compared to QC as a free drug (p < 0.001) and to quercetin-loaded AG-PVP (AG-PVP-QC) (p < 0.001) with enhanced apoptosis induction after the addition of HAp. Accordingly, this delivery platform ameliorated loading and sustained-release of QC, as well as its anticancer activity by releasing the drug at an effective therapeutic level over a long period to induce apoptosis. Thus, turning this drug delivery system into a potential candidate for further biomedical applications.