Biopharmaceutical and pharmacokinetic attributes to drive nanoformulations of small molecule tyrosine kinase inhibitors.

Buoyed by the discovery of small-molecule tyrosine kinase inhibitors (smTKIs), significant impact has been made in cancer chemotherapeutics. However, some of these agents still encounter off-target toxicities and suboptimal efficacies due to their inferior biopharmaceutical and/or pharmacokinetic properties. Almost all of these molecules exhibit significant inter- and intra-patient variations in plasma concentration-time profiles.

Facile fabrication of degradable, serrated polyethylene diacrylate microneedles using stereolithography.

Microneedles have the potential for minimally invasive drug delivery. However, they are constrained by absence of rapid, scalable fabrication methods to produce intricate arrays and serrations for enhanced adhesion. 3D printing techniques like stereolithography (SLA) are fast, scalable modalities but SLAs require non-degradable and stiff resins.

Supramolecular J- and H-Aggregation of Naphthalimide-Conjugated Dipeptide in Mixed-Solvent Systems and its Application in Cell Imaging.

In this work, a core-substituted NMI-conjugated dipeptide (4MNLV) was extensively studied in mixed solvent systems to explore the polarity effect on the self-assembly pattern and their photophysical property. 4MNLV adopted J- or H- type aggregation pattern depending upon the polarity index of the solvent system chosen. The self-assembly process was achieved through the anti-solvent effect.

Spatiotemporally Controlled Release of Etamsylate from Bioinspired Peptide-Functionalized Nanoparticles Arrests Bleeding Rapidly and Improves Clot Stability in a Rabbit Internal Hemorrhage Model.

Achieving rapid clotting and clot stability are important unmet goals of clinical management of noncompressible hemorrhage. This study reports the development of a spatiotemporally controlled release system of an antihemorrhagic drug, etamsylate, in the management of internal hemorrhage. Gly-Arg-Gly-Asp-Ser (GRGDS) peptide-functionalized chitosan nanoparticles, with high affinity to bind with the GPIIa/IIIb receptor of activated platelets, were loaded with the drug etamsylate (etamsylate-loaded GRGDS peptide-functionalized chitosan nanoparticles; EGCSNP).

A Lipophilic Salt Form to Enhance the Lipid Solubility and Certain Biopharmaceutical Properties of Lapatinib.

Lapatinib (LTP) commercially available as lapatinib ditosylate (LTP-DTS) salt is the only drug approved for the treatment of HER-positive metastatic breast cancer. A low and pH-dependent solubility results in poor and variable oral bioavailability, thus driving significant interest in molecular modification and formulation strategies of the drug. Furthermore, due to very high crystallinity, LTP and LTP-DTS have low solubility in lipid excipients, making it difficult to be delivered by lipid-based carrier systems.

Effect of probiotics supplementation on liver stiffness and steatosis in patients with NAFLD.

Background And Aim: To compare the effects of probiotics on liver stiffness and steatosis in obese and non-obese patients with nonalcoholic fatty liver disease (NAFLD),the pragmatic clinical trial included 50 obese body mass index (BMI) ≥25 kg/m and 50 non-obese NAFLD BMI <25 kg/m age and sex-matched patients.

Materials And Methods: Fibroscan with controlled attenuated parameter (CAP) was done at day 0 and at the end of 6 months. Probiotics supplementation was provided for both groups for 6 months along with lifestyle modifications.

Synergistic coupling between 3D bioprinting and vascularization strategies.

Three-dimensional (3D) bioprinting offers promising solutions to the complex challenge of vascularization in biofabrication, thereby enhancing the prospects for clinical translation of engineered tissues and organs. While existing reviews have touched upon 3D bioprinting in vascularized tissue contexts, the current review offers a more holistic perspective, encompassing recent technical advancements and spanning the entire multistage bioprinting process, with a particular emphasis on vascularization. The synergy between 3D bioprinting and vascularization strategies is crucial, as 3D bioprinting can enable the creation of personalized, tissue-specific vascular network while the vascularization enhances tissue viability and function.

Supramolecular Nanostructures for the Delivery of Peptides in Cancer Therapy.

Supramolecular nanostructured based delivery systems are emerging as a meaningful approach in the treatment of cancer, offering controlled drug release and improved therapeutic efficacy. The self-assembled structures can be small molecules, polymers, peptides, or proteins, which can be used and functionalized to achieve tailored release and target specific cells, tissues, or organs. These structures can improve the solubility and stability of drugs having low aqueous solubility by encapsulating and protecting them from degradation.

Vitamin D3-incorporated chitosan/collagen/fibrinogen scaffolds promote angiogenesis and endothelial transition via HIF-1/IGF-1/VEGF pathways in dental pulp stem cells.

Effective vascularization during wound healing remains a critical challenge in the regeneration of skin tissue. On the other hand, mesenchymal stem cell (MSC) to endothelial phenotype transition (MEnDoT) is a potential phenomenon grossly underexplored in vascularized skin tissue engineering. Vitamin D3 has a proven role in promoting MEnDoT.

3D Printing of Ti-6Al-4V-Based Porous-Channel Dental Implants: Computational, Biomechanical, and Cytocompatibility Analyses.

Loosening of dental implants due to resorption of the surrounding bone is one of the challenging clinical complications in prosthetic dentistry. Generally, stiffness mismatch between an implant and its surrounding bone is one of the major factors. In order to prevent such clinical consequences, it is essential to develop implants with customized stiffness.

Patient-specific femoral implant design using metamaterials for improving load transfer at proximal-lateral region of the femur.

Loading configuration of hip joint creates resultant bending effect on femoral implants. So, the lateral side of femoral implant which is under tension retracts from peri‑implant bone due to positive Poisson's ratio. This retraction of implant leads to load shielding and gap opening in proximal-lateral region, thereby allowing entry of wear particle to implant-bone interface.

A Micro-Scale Non-Linear Finite Element Model to Optimize the Mechanical Behavior of Bioprinted Constructs.

Extrusion-based bioprinting is an enabling biofabrication technique that is used to create heterogeneous tissue constructs according to patient-specific geometries and compositions. The optimization of bioinks as per requirements for specific tissue applications is an essential exercise in ensuring clinical translation of the bioprinting technologies. Most notably, optimum hydrogel polymer concentrations are required to ensure adequate mechanical properties of bioprinted constructs without causing significant shear stresses on cells.

Experimental and simulation investigation of surgical needle insertion into soft tissue mimic biomaterial for minimally invasive surgery (MIS).

The surgical needle insertion process is widely applied in medical interference. During the insertion process, the inhomogeneity and denseness of the soft tissues make it tough to detect the essential tissue damage, a rupture occurs that contains huge forces and material deformations. This study is very important, as all the above-mentioned factors are very significant for modern invasive surgery so that the success rate of the surgery can increase and the patient recovers smoothly.

Simulation and experimental investigation of the surgical needle deflection model during the rotational and steady insertion process.

Needle insertion is executed in numerous medical and brachytherapy events. Exact needle insertion into inhomogeneous soft biological tissue is of useful importance due to its significance in clinical diagnosis (especially percutaneous) and treatments. The surgical needles used in such processes can deflect during the percutaneous process.

Mesenchymal Stem Cell-Derived Extracellular Vesicles for Therapeutic Use and in Bioengineering Applications.

Extracellular vesicles (EVs) are small lipid bilayer-delimited particles that are naturally released from cells into body fluids, and therefore can travel and convey regulatory functions in the distal parts of the body. EVs can transmit paracrine signaling by carrying over cytokines, chemokines, growth factors, interleukins (ILs), transcription factors, and nucleic acids such as DNA, mRNAs, microRNAs, piRNAs, lncRNAs, sn/snoRNAs, mtRNAs and circRNAs; these EVs travel to predecided destinations to perform their functions. While mesenchymal stem cells (MSCs) have been shown to improve healing and facilitate treatments of various diseases, the allogenic use of these cells is often accompanied by serious adverse effects after transplantation.

Strategies for 3D bioprinting of spheroids: A comprehensive review.

Biofabricated tissues have found numerous applications in tissue engineering and regenerative medicine in addition to the promotion of disease modeling and drug development and screening. Although three-dimensional (3D) printing strategies for designing and developing customized tissue constructs have made significant progress, the complexity of innate multicellular tissues hinders the accurate evaluation of physiological responses in vitro. Cellular aggregates, such as spheroids, are 3D structures where multiple types of cells are co-cultured and organized with endogenously secreted extracellular matrix and are designed to recapitulate the key features of native tissues more realistically.

Ethical challenges with 3D bioprinted tissues and organs.

3D Bioprinting is fast advancing to offer capabilities to process living cells into geometrically and functionally complex tissue and organ substitutes. As bioprinted constructs are making their way into clinic, the bioprinting community needs to consider the responsible innovation and translation of the bioprinted tissues and organs.

Study of the surgical needle and biological soft tissue interaction phenomenon during insertion process for medical application: A Survey.

The insertion of the surgical needle in soft tissue has involved significant interest in the current time because of its purpose in minimally invasive surgery (MIS) and percutaneous events like biopsies, PCNL, and brachytherapy. This study represents a review of the existing condition of investigation on insertion of a surgical needle in biological living soft tissue material. As observes the issue from numerous phases, like, analysis of the cutting forces modeling (insertion), tissue material deformation, analysis of the needle deflection for the period of the needle insertion, and the robot-controlled insertion procedures.

Probing the Influence of Hybrid Thread Design on Biomechanical Response of Dental Implants: Finite Element Study and Experimental Validation.

This study aimed to perform quantitative biomechanical analysis for probing the effect of varying thread shapes in an implant for improved primary stability in prosthodontics surgery. Dental implants were designed with square (SQR), buttress (BUT), and triangular (TRI) thread shapes or their combinations. Cone-beam computed tomography images of mandible molar zones in human subjects belonging to three age groups were used for virtual implantation of the designed implants, to quantify patient-specific peri-implant bone microstrain, using finite element analyses.

3D Coaxial Bioprinting: Process Mechanisms, Bioinks and Applications.

In the last decade, bioprinting has emerged as a facile technique for fabricating tissues constructs mimicking the architectural complexity and compositional heterogeneity of native tissues. Amongst different bioprinting modalities, extrusion-based bioprinting (EBB) is the most widely used technique. Coaxial bioprinting, a type of EBB, enables fabrication of concentric cell-material layers and enlarges the scope of EBB to mimic several key aspects of native tissues.

Probing combinational influence of design variables on bone biomechanical response around dental implant-supported fixed prosthesis.

This study aimed to understand the effect of physiological and dental implant-related parameter variations on the osseointegration for an implant-supported fixed prosthesis. Eight design factors were considered (implant shape, diameter, and length; thread pitch, depth, and profile; cantilever [CL] length and implant-loading protocol). Total 36 implantation scenarios were simulated using finite element method based on Taguchi L orthogonal array.

Modelling cell deformations in bioprinting process using a multicompartment-smooth particle hydrodynamics approach.

Bioprinting using cell-laden bioink is a rapidly emerging additive manufacturing method to fabricate engineered tissue constructs and in vitro models of disease biology. Amongst different bioprinting modalities, extrusion-based bioprinting is the most conveniently adopted technique due to its affordability. Bioinks consisting of living cells are suspended in hydrogels and extruded through syringe-needle assemblies, which subsequently undergo gelation at the collector plate.

Finite element analysis of the influence of cyclic strain on cells anchored to substrates with varying properties.

The response of cytoskeleton to mechanical cues plays a pivotal role in understanding several aspects of cellular growth, migration, and cell-cell and cell-matrix interactions under normal and diseased conditions. Finite element analysis (FEA) has become a powerful computational technique to study the response of cytoskeleton in the maintenance of overall cellular mechanics. With the revelation of role of external mechanical microenvironment on cell mechanics, FEA models have also been developed to simulate the effect of substrate stiffness on the mechanical properties of cancer cells.

Design of patient specific bone stiffness mimicking scaffold.

The difference in stiffness of a patient's bone and bone implant causes stress shielding. Thus, implants which match the stiffness of bone of the patient result in better bone growth and osseointegration. Variation in porosity is one of the methods to obtain implants with different stiffness values.