Renewable Electroconductive Hydrogels for Accelerated Diabetic Wound Healing and Motion Monitoring.

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes mellitus, may result in an amputation. Natural and renewable hydrogels are desirable materials for DFU dressings due to their outstanding biosafety and degradability. However, most hydrogels are usually only used for wound repair and cannot be employed to monitor motion because of their inherent poor mechanical properties and electrical conductivity. Given that proper wound stretching is beneficial for wound healing, the development of natural hydrogel patches integrated with wound repair properties and motion monitoring was expected to achieve efficient and accurate wound healing. Here, we designed a dual-network (chitosan and sodium alginate) hydrogel embedded with lignin-Ag and quercetin-melanin nanoparticles to achieve efficient wound healing and motion monitoring. The double network formed by the covalent bond and electrostatic interaction confers the hydrogel with superior mechanical properties. Instead of the usual chemical reagents, genipin extracted from Gardenia was used as a cross-linking agent for the hydrogel and consequently improved its biosafety. Furthermore, the incorporation of lignin-Ag nanoparticles greatly enhanced the mechanical strength, antibacterial efficacy, and conductivity of the hydrogel. The electrical conductivity of hydrogels gives them the capability of motion monitoring. The motion sensing mechanism is that stretching of the hydrogel induced by motion changes the conductivity of the hydrogel, thus converting the motion into an electrical signal. Meanwhile, quercetin-melanin nanoparticles confer exceptional adhesion, antioxidant, and anti-inflammatory properties to the hydrogels. The system ultimately achieved excellent wound repair and motion monitoring performance and was expected to be used for stretch-assisted safe and accurate wound repair in the future.

A review of current effective COVID-19 testing methods and quality control.

COVID-19 is a highly infectious disease caused by the SARS-CoV-2 virus, which primarily affects the respiratory system and can lead to severe illness. The virus is extremely contagious, early and accurate diagnosis of SARS-CoV-2 is crucial to contain its spread, to provide prompt treatment, and to prevent complications. Currently, the reverse transcriptase polymerase chain reaction (RT-PCR) is considered to be the gold standard for detecting COVID-19 in its early stages. In addition, loop-mediated isothermal amplification (LMAP), clustering rule interval short palindromic repeats (CRISPR), colloidal gold immunochromatographic assay (GICA), computed tomography (CT), and electrochemical sensors are also common tests. However, these different methods vary greatly in terms of their detection efficiency, specificity, accuracy, sensitivity, cost, and throughput. Besides, most of the current detection methods are conducted in central hospitals and laboratories, which is a great challenge for remote and underdeveloped areas. Therefore, it is essential to review the advantages and disadvantages of different COVID-19 detection methods, as well as the technology that can enhance detection efficiency and improve detection quality in greater details.

Enhancing Bone Grafting Outcomes: A Comprehensive Review of Antibacterial Artificial Composite Bone Scaffolds.

Bone defects and dysfunctions are prevalent among patients, resulting from various causes such as trauma, tumors, congenital malformations, inflammation, and infection. The demand for bone defect repair materials is second only to blood transfusions. Artificial bone composites offer numerous advantages for bone damage repair, including their availability, absence of rejection or immune reactions, high malleability, exceptional mechanical strength, and outstanding biocompatibility. However, bacterial infections frequently occur during bone transplantation or on graft material structures, leading to severe complications such as osteomyelitis and osteoporosis. Moreover, existing osteogenic materials alone are inadequate to address the challenges posed by traumatic infections, presenting a significant hurdle for clinicians in reconstructing infectious bone defects. Consequently, it is crucial to functionalize artificial bone composites to facilitate effective bone repair and regeneration. Notably, antibacterial capabilities play a critical role in preventing and treating infectious bone defects, and current research is focusing on the interface between artificial bone composites and antibacterial treatments. This article provides an extensive review of the current state of artificial composite bone scaffolds with antibacterial properties for infection prevention in bone grafting.

Molecularly Imprinted Polymer-Based Sensors for the Detection of Skeletal- and Cardiac-Muscle-Related Analytes.

Molecularly imprinted polymers (MIPs) are synthetic polymers with specific binding sites that present high affinity and spatial and chemical complementarities to a targeted analyte. They mimic the molecular recognition seen naturally in the antibody/antigen complementarity. Because of their specificity, MIPs can be included in sensors as a recognition element coupled to a transducer part that converts the interaction of MIP/analyte into a quantifiable signal. Such sensors have important applications in the biomedical field in diagnosis and drug discovery, and are a necessary complement of tissue engineering for analyzing the functionalities of the engineered tissues. Therefore, in this review, we provide an overview of MIP sensors that have been used for the detection of skeletal- and cardiac-muscle-related analytes. We organized this review by targeted analytes in alphabetical order. Thus, after an introduction to the fabrication of MIPs, we highlight different types of MIP sensors with an emphasis on recent works and show their great diversity, their fabrication, their linear range for a given analyte, their limit of detection (LOD), specificity, and reproducibility. We conclude the review with future developments and perspectives.

3D printing of self-standing and vascular supportive multimaterial hydrogel structures for organ engineering.

Three dimensional printable formulation of self-standing and vascular-supportive structures using multi-materials suitable for organ engineering is of great importance and highly challengeable, but, it could advance the 3D printing scenario from printable shape to functional unit of human body. In this study, the authors report a 3D printable formulation of such self-standing and vascular-supportive structures using an in-house formulated multi-material combination of albumen/alginate/gelatin-based hydrogel. The rheological properties and relaxation behavior of hydrogels were analyzed before the printing process. The suitability of the hydrogel in 3D printing of various customizable and self-standing structures, including a human ear model, was examined by extrusion-based 3D printing. The structural, mechanical, and physicochemical properties of the printed scaffolds were studied systematically. Results supported the 3D printability of the formulated hydrogel with self-standing structures, which are customizable to a specific need. In vitro cell experiment showed that the formulated hydrogel has excellent biocompatibility and vascular supportive behavior with the extent of endothelial sprout formation when tested with human umbilical vein endothelial cells. In conclusion, the present study demonstrated the suitability of the extrusion-based 3D printing technique for manufacturing complex shapes and structures using multi-materials with high fidelity, which have great potential in organ engineering.

Impact of Induced Pluripotent Stem Cells in Bone Repair and Regeneration.

PURPOSE OF REVIEW: The main objective of this article is to investigate the current trends in the use of induced pluripotent stem cells (iPSCs) for bone tissue repair and regeneration. RECENT FINDINGS: Pluripotent stem cell-based tissue engineering has extended innovative therapeutic approaches for regenerative medicine. iPSCs have shown osteogenic differentiation capabilities and would be an innovative resource of stem cells for bone tissue regenerative applications. This review recapitulates the current knowledge and recent progress regarding utilization of iPSCs for bone therapy. A review of current findings suggests that a combination of a three-dimensional scaffolding system with iPSC technology to mimic the physiological complexity of the native stem cell niche is highly favorable for bone tissue repair and regeneration.

Biomimetic Nanohydroxyapatite Synthesized With/Without Tris-Buffered Simulated Body Fluid: A Comparative Analysis.

Nano hydroxyapatite (nHAp) mimics the inorganic phase of hard tissue such as bone and teeth and, thus, has a wide range of clinical applications. The present study reports on the biomimetic synthesis of nHAp with and without Tris-buffered simulated body fluid (SBF) and investigated the role of buffering conditions on nHAp formation. The hypothesis of this study was that the nucleation and growth rate of nHAp may depend on buffering conditions during the precipitation process. The results of this study suggest that both of the above methods effectively synthesized carbonated "bone-like" nHAp. However, an increased incubation period of 8 hrs was necessary for nHAp synthesized using non Tris-buffered SBF as compared to Tris-buffered SBF which synthesized nHAp in just 3 hrs. Interestingly, there was no change in the chemical functionality for both samples. XRD and TGA analysis confirmed that Tris-buffered SBF facilitated more carbonate ion substitution than the non-Tris-buffered SBF approach. Therefore, this study concluded for the first time that the addition of Tris in SBF accelerates nHAp formation with more carbonate ion substitution. Nevertheless, carbonate ion substituted nHAp could also be synthesized using non Tris-buffered SBF, but would require longer incubation periods. This analysis highlights the importance of pH stability in the SBF for biomimetic nHAp synthesis which is useful for the synthesis of nHAp for a wide range of biomedical applications.

Development of Egg Shell Derived Carbonated Apatite Nanocarrier System for Drug Delivery.

Carbonated apatite has a chemical composition quite similar to biological apatite found in native bone. The incorporation of carbonate (CO2-3) ions groups into the apatitic crystal structure can tailor its crystallinity, solubility and biological activity that benefit the bone repair and regeneration. In this study, we report a simple and elegant method of synthesizing carbonated calcium deficient hydroxyapatite (ECCDHA) nanoparticles from egg shell wastes and its efficacy has been compared with synthetic calcium deficient hydroxyapatite (SCDHA) nanoparticles. Egg shell contains about 94% of calcium carbonate. Fourier transform infrared (FT-IR) spectroscopy results confirmed the carbonate substitution in the apatite as B-type and CHNS/O elemental analysis showed 6 wt.% of carbonate content in ECCDHA. Energy dispersive spectroscopy (EDS) analysis confirmed the presence of biologically relevant elements such as magnesium, strontium, fluoride, potassium etc., in ECCDHA inherited from the egg shell. In vitro cell culture studies confirmed that the ECCDHA is cellular compatible and it has enhanced cell adhesion and proliferation of L6 myoblast cells as compared to SCDHA. The potential of ECCDHA suitable for bone drug applications was tested with an antibiotic drug, doxycycline. The results showed higher drug loading and releasing for ECCDHA as compared to SCDHA during the period of study. Based on these results, the ECCDHA may be considered as a potential bone substitute and drug carrier system.

Development of Silver-Based Bactericidal Composite Nanofibers by Airbrushing.

In this article, we report a simple, cost-effective and eco-friendly method of airbrushing for the fabrication of antibacterial composite nanofibers using Nylon-6 and silver chloride (AgCl). The Nylon-6 is a widely used polymer for various biomedical applications because of its excellent biocompatibility and mechanical properties. Similarly, silver has also been known for their antibacterial, antifungal, antiviral, and anti-inflammatory properties. In order to enhance the antibacterial functionality of the Nylon-6, composite nanofibers in combination with AgCl have been fabricated using airbrush method. The chemical functional groups and morphological studies of the airbrushed Nylon-6/AgCl composite nanofibers were carried out by FTIR and SEM, respectively. The antibacterial activity of airbrushed Nylon-6/AgCl composite nanofibers was evaluated using Gram +ve (Staphylococcus aureus) and Gram -ve (Escherichia coli) bacterial strains. The results showed that the airbrushed Nylon-6/AgCl composite nanofibers have better antibacterial activity against the tested bacterial strains than the airbrushed Nylon-6 nanofibers. Therefore, the airbrushed Nylon-6/AgCl composite nanofibers could be used as a potential antibacterial scaffolding system for tissue engineering and regenerative medicine.

Bioconjugated Hydrogels for Tissue Engineering and Regenerative Medicine.

Hydrogels are hydrophilic polymer networks with high water content, which have played an important role as scaffolds for cells, as carriers for various biomolecules (e.g., drugs, genes, and soluble factors), and as injectable biomaterials in tissue engineering (TE) and regenerative medicine. Bioconjugation is an approach for improving the performance of hydrogels using cell-responsive components, such as proteins and peptides, which have high affinity to regulate cellular behaviors and tissue morphogenesis. However, the current knowledge on the role of those bioconjugated moieties in controlling cellular functions and tissue morphogenesis and bioconjugation methods are limited in the context of TE and organogenesis. Moreover, micro- and nanofabrication techniques have been used to manipulate bioconjugated hydrogels for regulating cell behaviors and function. This Review therefore describes synthesis, characteristics, and manipulation of various bioconjugated hydrogels and their potential in TE applications with special emphasis on preclinical/clinical translation.

The use of microtechnology and nanotechnology in fabricating vascularized tissues.

Tissue engineering (TE) is a multidisciplinary research area that combines medicine, biology, and material science. In recent decades, microtechnology and nanotechnology have also been gradually integrated into this field and have become essential components of TE research. Tissues and complex organs in the body depend on a branched blood vessel system. One of the main objectives for TE researchers is to replicate this vessel system and obtain functional vascularized structures within engineered tissues or organs. With the help of new nanotechnology and microtechnology, significant progress has been made. Achievements include the design of nanoscale-level scaffolds with new functionalities, development of integrated and rapid nanotechnology methods for biofabrication of vascular tissues, discovery of new composite materials to direct differentiation of stem and inducible pluripotent stem cells into the vascular phenotype. Although numerous challenges to replicating vascularized tissue for clinical uses remain, the combination of these new advances has yielded new tools for producing functional vascular tissues in the near future.

Application of 3D printing on the design and development of pharmaceutical oral dosage forms.

3D printing technologies confer an unparalleled degree of control over the material distribution on the structures they produce, which has led them to become an extremely attractive research topic in pharmaceutical dosage form development, especially for the design of personalized treatments. With fine tuning in material selection and careful design, these technologies allow to tailor not only the amount of drug administered but the biopharmaceutical behaviour of the dosage forms as well. While fused deposition modelling (FDM) is still the most studied 3D printing technology in this area, others are gaining more relevance, which has led to many new and exciting dosage forms developed during 2022 and 2023. Considering that these technologies, in time, will join the current manufacturing methods and with the ever-increasing knowledge on this topic, our review aims to explore the advantages and limitations of 3D printing technologies employed in the design and development of pharmaceutical oral dosage forms, giving special focus to the most important aspects governing the resulting drug release profiles.

Human neural stem cell secretome relieves endoplasmic reticulum stress-induced apoptosis and improves neuronal functions after traumatic brain injury in a rat model.

Neural stem cell secretome (NSC-S) plays an important role in neuroprotection and recovery. Studies have shown that endoplasmic reticulum stress (ER stress) is involved in the progression of traumatic brain injury (TBI) and is a crucial cause of secondary damage and neuronal death after brain injury. Whether NSC-S is engaged in ER stress and ER stress-mediated neuronal apoptosis post-TBI has not been investigated. In the study, the Feeney SD male rat model was established. The results showed that NSC-S treatment significantly improved the behavior of rats with TBI. In addition, NSC-S relieved ER stress in TBI rats and was observed by transmission electron microscopy and western blot. The specific mechanism was further elucidated that restoration was achieved by alleviating the PERK-eIF2α pathway and thus protecting neurons from apoptosis. Notably, the discovery of calumenin (CALU) in NSC-S by liquid chromatography-tandem mass spectrometry (LC-MS/MS/MS) may be related to the protective effect of NSC-S on ER stress in neurons. Also, the mechanism by which it functions may be related to ubiquitination. In summary, NSC-S improved prognosis and ER stress in TBI rats and might be a promising treatment for relieving TBI.

Calcium Carbonate/Polydopamine Composite Nanoplatform Based on TGF-ß Blockade for Comfortable Cancer Immunotherapy.

Cancer pain seriously reduces the quality of life of cancer patients. However, most research about cancer focuses solely on inhibiting tumor growth, neglecting the issue of cancer pain. Therefore, the development of therapeutic agents with both tumor suppression and cancer pain relief is crucial to achieve human-centered treatment. Here, the work reports curcumin (CUR) and ropivacaine (Ropi) coincorporating CaCO3/PDA nanoparticles (CaPNMCUR+Ropi) that realized efficient tumor immunotherapy and cancer pain suppression. The therapeutic efficiency and mechanism are revealed in vitro and in vivo. The results indicate that CaPNMCUR+Ropi underwent tumor microenvironment-responsive degradation and realized rapid release of calcium ions, Ropi, and CUR. The excessive intracellular calcium triggered the apoptosis of tumor cells, and the transient pain caused by the tumor injection was relieved by Ropi. Simultaneously, CUR reduced the levels of immunosuppressive factor (TGF-ß) and inflammatory factor (IL-6, IL-1ß, and TNF-α) in the tumor microenvironment, thereby continuously augmenting the immune response and alleviating inflammatory pain of cancer animals. Meanwhile, the decrease of TGF-ß leads to the reduction of transient receptor potential vanilloid 1 (TRPV1) expression, thereby alleviating hyperalgesia and achieving long-lasting analgesic effects. The design of the nanosystem provides a novel idea for human-centered tumor treatment in the future.

Gradient nanofiber scaffolds for tissue engineering.

Scaffolds are one of the key factors for the success of tissue engineering, in particular when dealing with anchorage-dependent cells. The concept of using scaffolds in tissue engineering lies in mimicking the physical, chemical and biological features of native extracellular matrix (ECM) in order to support cell function, which in turn regulates cellular microenvironment that directs cell growth and subsequent tissue formation. Nanofibers fabricated from both synthetic and natural polymers are being used as scaffolds in many tissue engineering applications. At the molecular level, native ECM is made up of a gradient of fibrous proteins and polysaccharides that are nanoscale structures. The gradient cues of ECM, directs critical cell behaviors such as alignment, motility and differentiation, particularly in the region between soft and hard tissues called interfacial tissue. Therefore, it is essential to develop gradient nanofiber scaffolds particularly for interfacial tissue engineering applications. Keeping these points in view, in this article, we review the recent developments of gradient nanofiber scaffolds, their design strategies, and their applications in tissue engineering.

Preparation and Characterization of Nano-Silver-Loaded Antibacterial Membrane via Coaxial Electrospinning.

The coaxial electrospinning process has been widely used in the biomedical field, and its process parameters affect product quality seriously. In this paper, the influence of key process parameters of coaxial electrostatic spinning (solution concentration, electrospinning voltage, acceptance distance and liquid supply velocity) on the preparation of a membrane with Chitosan, Polyethylene oxide and nano-silver as the core layer and Polycaprolactone as the shell layer was studied. The optimal combination of key process parameters was obtained by using an orthogonal test, scanning electron microscope, transmission electron microscope and macro-characterization diagram. The results showed that the coaxial electrospun membrane had good mechanical properties (tensile strength is about 2.945 Mpa), hydrophilicity (the water contact angle is about 72.28°) and non-cytotoxicity, which was conducive to cell adhesion and proliferation. The coaxial electrospun membrane with nano-silver has an obvious inhibitory effect on Escherichia coli and Staphylococcus aureus. In summary, the coaxial electrospun membrane that we produced is expected to be used in clinical medicine, such as vascular stent membranes and bionic blood vessels.

A 5 + 1-Axis 3D Printing Platform for Producing Customized Intestinal Fistula Stents.

Tailored intestinal fistula stents with a hollow bent pipe structure prepared by using a three-axis bio-printing platform are often unsuitable due to low printing efficiency and quality caused by the unavoidable need for a supporting structure. Herein, a 5 + 1-axis 3D printing platform was built and developed for producing support-free intestinal fistula stents. A 3D model of the target stent shape and dimensions was treated by a dynamic slicing algorithm, which was then used to prepare a motion control code. Our printing method showed improved printing efficiency, superior stent surface properties and structure and ideal elasticity and mechanical strength to meet the mechanical requirements of the human body. Static simulations showed the importance of axial printing techniques, whereas the stent itself was shown to have excellent biocompatibility with wettability and cell proliferation tests. We present a customizable, efficient, and high-quality method with the potential for preparing bespoke stents for treating intestinal fistulas.

Latest developments in engineered skeletal muscle tissues for drug discovery and development.

INTRODUCTION: With the advances in skeletal muscle tissue engineering, new platforms have arisen with important applications in biology studies, disease modeling, and drug testing. Current developments highlight the quest for engineering skeletal muscle tissues with higher complexity . These new human skeletal muscle tissue models will be powerful tools for drug discovery and development and disease modeling. AREAS COVERED: The authors review the latest advances in in vitro models of engineered skeletal muscle tissues used for testing drugs with a focus on the use of four main cell culture techniques: Cell cultures in well plates, in microfluidics, in organoids, and in bioprinted constructs. Additional information is provided on the satellite cell niche. EXPERT OPINION: In recent years, more sophisticated in vitro models of skeletal muscle tissues have been fabricated. Important developments have been made in stem cell research and in the engineering of human skeletal muscle tissue. Some platforms have already started to be used for drug testing, notably those based on the parameters of hypertrophy/atrophy and the contractibility of myotubes. More developments are expected through the use of multicellular types and multi-materials as matrices . The validation and use of these models in drug testing should now increase.

Bioprinting and biomaterials for dental alveolar tissue regeneration.

Three dimensional (3D) bioprinting is a powerful tool, that was recently applied to tissue engineering. This technique allows the precise deposition of cells encapsulated in supportive bioinks to fabricate complex scaffolds, which are used to repair targeted tissues. Here, we review the recent developments in the application of 3D bioprinting to dental tissue engineering. These tissues, including teeth, periodontal ligament, alveolar bones, and dental pulp, present cell types and mechanical properties with great heterogeneity, which is challenging to reproduce in vitro. After highlighting the different bioprinting methods used in regenerative dentistry, we reviewed the great variety of bioink formulations and their effects on cells, which have been established to support the development of these tissues. We discussed the different advances achieved in the fabrication of each dental tissue to provide an overview of the current state of the methods. We conclude with the remaining challenges and future needs.

Multifunctional Oxygen-Generating Nanoflowers for Enhanced Tumor Therapy.

Sonodynamic therapy (SDT) and chemotherapy have received great attention as effective methods for tumor treatment. However, the inherent hypoxia of the tumor greatly hinders its therapeutic efficacy. In this work, a tumor microenvironment-responsive biodegradable nanoplatform SiO2-MnO2-PEG-Ce6&DOX (designated as SMPC&D) is fabricated by encapsulating manganese oxide (MnO2) into silica nanoparticles and anchoring poly(ethylene glycol) (PEG) onto the surface for tumor hypoxia relief and delivery, then loaded with sonosensitizer Chlorin e6 (Ce6) and chemotherapeutic drug doxorubicin (DOX) for hypoxic tumor treatment. We evaluated the physicochemical properties of SMPC&D nanoparticles and the tumor therapeutic effects of chemotherapy and SDT under ultrasound stimulation in vitro and in vivo. After endocytosis by tumor cells, highly expressed glutathione (GSH) triggers biodegradation of the nanoplatform and MnO2 catalyzes hydrogen peroxide (H2O2) to generate oxygen (O2), thereby alleviating tumor hypoxia. Depleting GSH and self-supplying O2 effectively improve the SDT efficiency both in vitro and in vivo. Ultrasonic stimulation promoted the release and cellular uptake of chemotherapy drugs. In addition, the relieved hypoxia reduced the efflux of chemotherapy drugs by downregulating the expression of the P-gp protein, which jointly improved the effect of chemotherapy. This study demonstrates that the degradable SMPC&D as a therapeutic agent can achieve efficient chemotherapy and SDT synergistic therapy for hypoxic tumors.