30 research outputs found

    3D Bioprinting tissue analogs: Current development and translational implications

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    Three-dimensional (3D) bioprinting is a promising and rapidly evolving technology in the field of additive manufacturing. It enables the fabrication of living cellular constructs with complex architectures that are suitable for various biomedical applications, such as tissue engineering, disease modeling, drug screening, and precision regenerative medicine. The ultimate goal of bioprinting is to produce stable, anatomically-shaped, human-scale functional organs or tissue substitutes that can be implanted. Although various bioprinting techniques have emerged to develop customized tissue-engineering substitutes over the past decade, several challenges remain in fabricating volumetric tissue constructs with complex shapes and sizes and translating the printed products into clinical practice. Thus, it is crucial to develop a successful strategy for translating research outputs into clinical practice to address the current organ and tissue crises and improve patients' quality of life. This review article discusses the challenges of the existing bioprinting processes in preparing clinically relevant tissue substitutes. It further reviews various strategies and technical feasibility to overcome the challenges that limit the fabrication of volumetric biological constructs and their translational implications. Additionally, the article highlights exciting technological advances in the 3D bioprinting of anatomically shaped tissue substitutes and suggests future research and development directions. This review aims to provide readers with insight into the state-of-the-art 3D bioprinting techniques as powerful tools in engineering functional tissues and organs

    Direct 3D printed biocompatible microfluidics: assessment of human mesenchymal stem cell differentiation and cytotoxic drug screening in a dynamic culture system

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    Abstract Background In vivo-mimicking conditions are critical in in vitro cell analysis to obtain clinically relevant results. The required conditions, comparable to those prevalent in nature, can be provided by microfluidic dynamic cell cultures. Microfluidics can be used to fabricate and test the functionality and biocompatibility of newly developed nanosystems or to apply micro- and nanoelectromechanical systems embedded in a microfluidic system. However, the use of microfluidic systems is often hampered by their accessibility, acquisition cost, or customization, especially for scientists whose primary research focus is not microfluidics. Results Here we present a method for 3D printing that can be applied without special prior knowledge and sophisticated equipment to produce various ready-to-use microfluidic components with a size of 100 µm. Compared to other available methods, 3D printing using fused deposition modeling (FDM) offers several advantages, such as time-reduction and avoidance of sophisticated equipment (e.g., photolithography), as well as excellent biocompatibility and avoidance of toxic, leaching chemicals or post-processing (e.g., stereolithography). We further demonstrate the ease of use of the method for two relevant applications: a cytotoxicity screening system and an osteoblastic differentiation assay. To our knowledge, this is the first time an application including treatment, long-term cell culture and analysis on one chip has been demonstrated in a directly 3D-printed microfluidic chip. Conclusion The direct 3D printing method is tested and validated for various microfluidic components that can be combined on a chip depending on the specific requirements of the experiment. The ease of use and production opens up the potential of microfluidics to a wide range of users, especially in biomedical research. Our demonstration of its use as a cytotoxicity screening system and as an assay for osteoblastic differentiation shows the methods potential in the development of novel biomedical applications. With the presented method, we aim to disseminate microfluidics as a standard method in biomedical research, thus improving the reproducibility and transferability of results to clinical applications. Graphical Abstrac

    Challenges in Bone Tissue Regeneration: Stem Cell Therapy, Biofunctionality and Antimicrobial Properties of Novel Materials and Its Evolution

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    An aging population leads to increasing demand for sustained quality of life with the aid of novel implants. Patients expect fast healing and few complications after surgery. Increased biofunctionality and antimicrobial behavior of implants, in combination with supportive stem cell therapy, can meet these expectations. Recent research in the field of bone implants and the implementation of autologous mesenchymal stem cells in the treatment of bone defects is outlined and evaluated in this review. The article highlights several advantages, limitations and advances for metal-, ceramic- and polymer-based implants and discusses the future need for high-throughput screening systems used in the evaluation of novel developed materials and stem cell therapies. Automated cell culture systems, microarray assays or microfluidic devices are required to efficiently analyze the increasing number of new materials and stem cell-assisted therapies. Approaches described in the literature to improve biocompatibility, biofunctionality and stem cell differentiation efficiencies of implants range from the design of drug-laden nanoparticles to chemical modification and the selection of materials that mimic the natural tissue. Combining suitable implants with mesenchymal stem cell treatment promises to shorten healing time and increase treatment success. Most research studies focus on creating antibacterial materials or modifying implants with antibacterial coatings in order to address the increasing number of complications after surgeries that are mostly caused by bacterial infections. Moreover, treatment of multiresistant pathogens will pose even bigger challenges in hospitals in the future, according to the World Health Organization (WHO). These antibacterial materials will help to reduce infections after surgery and the number of antibiotic treatments that contribute to the emergence of new multiresistant pathogens, whilst the antibacterial implants will help reduce the amount of antibiotics used in clinical treatment

    Synergy of R‑(–)carvone and cyclohexenone‑based carbasugar precursors with antibiotics to enhance antibiotic potency and inhibit biofilm formation

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    The widespread use of antibiotics in recent decades has been a major factor in the emergence of antibiotic resistances. Antibiotic-resistant pathogens pose increasing challenges to healthcare systems in both developing and developed countries. To counteract this, the development of new antibiotics or adjuvants to combat existing resistance to antibiotics is crucial. Glycomimetics, for example carbasugars, offer high potential as adjuvants, as they can inhibit metabolic pathways or biofilm formation due to their similarity to natural substrates. Here, we demonstrate the synthesis of carbasugar precursors (CSPs) and their application as biofilm inhibitors for E. coli and MRSA, as well as their synergistic effect in combination with antibiotics to circumvent biofilm-induced antibiotic resistances. This results in a biofilm reduction of up to 70% for the CSP rac-7 and a reduction in bacterial viability of MRSA by approximately 45% when combined with the otherwise ineffective antibiotic mixture of penicillin and streptomycin

    Efficient Synthesis and X-ray Structure of [1,2,4]Triazolo[4,3-a]pyridines via Oxidative Cyclization Using N-Chlorosuccinimide (NCS)

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    Triazolopyridines are a family of compounds that, owing to their biological activity, have many pharmaceutical applications. In this study, 3-(pyridine-4-yl)-[1,2,4]triazolo[4,3-a]pyridine and 6-bromo-3-(pyridine-4-yl)-[1,2,4]triazolo[4,3-a]pyridine were synthesized by using the chlorinated agent NCS for hydrazones under very mild conditions. The characterization of these compounds was achieved by 1H NMR, 13C NMR, FTIR, MS and X-ray diffraction. The compound 3-(pyridine-4-yl)-[1,2,4]triazolo[4,3-a]pyridine was crystallized in the monoclinic space group P 21/c with a = 15.1413(12), b = 6.9179(4), c = 13.0938(8) Å, β = 105.102(6)°, V = 1324.16(16)Å3, Z = 4, and R = 0.0337. Also compound 6-bromo-3-(pyridine-4-yl)-[1,2,4]triazolo[4,3-a]pyridine was crystallized in the monoclinic space group P 21/c with a = 14.3213(11), b = 6.9452(4) (4), c = 12.6860(8)Å, β = 100.265(6)°, V = 1241.62(14)Å3, Z = 4, and R = 0.0561
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