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Overall, this study demonstrated the versatile therapeutic effects of a novel composite hydrogel ALG-HA with Ly-PRF, which optimizes a promising vascularized substitution strategy for improving cardiac function after MI.The combination of tumor ablation and immunotherapy is a promising strategy against tumor relapse and metastasis. Photothermal therapy (PTT) triggers the release of tumor-specific antigens and damage associated molecular patterns (DAMPs) in-situ. However, the immunosuppressive tumor microenvironment restrains the activity of the effector immune cells. Therefore, systematic immunomodulation is critical to stimulate the tumor microenvironment and augment the anti-tumor therapeutic effect. To this end, polyethylene glycol (PEG)-stabilized platinum (Pt) nanoparticles (Pt NPs) conjugated with a PD-L1 inhibitor (BMS-1) through a thermo-sensitive linkage were constructed. Upon near-infrared (NIR) exposure, BMS-1 was released and maleimide (Mal) was exposed on the surface of Pt NPs, which captured the antigens released from the ablated tumor cells, resulting in the enhanced antigen internalization and presentation. In addition, the Pt NPs acted as immune adjuvants by stimulating dendritic cells (DCs) maturation. Furthermore, BMS-1 relieved T cell exhaustion and induced the infiltration of effector T cells into the tumor tissues. Thus, Pt NPs can ablate tumors through PTT, and augment the anti-tumor immune response through enhanced antigen presentation and T cells infiltration, thereby preventing tumor relapse and metastasis.Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy. Herein, a pH-responsive gold nanoassembly is designed to overcome these problems. Polyethylene glycol linked raltitrexed (RTX, target ligand and chemotherapy drug) and two tertiary amine molecules (1-(2-aminoethyl) pyrrolidine and N, N-dibutylethylenediamine) are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX). The Au-NNP (RTX) nanoassembly could remain at about 160 nm at the blood circulation (pH 7.4), while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH (pH 6.8). This pH-responsive disassembly behavior endows Au-NNP(RTX) better tumor tissue permeability through the better diffusion brought by the size reduction. Meanwhile, after disassembly, more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability. Most importantly, the results show that Au-NNP(RTX) possesses of high tumor accumulation and effective tumor penetration, thereby enhancing the tumor chemo-radiotherapy efficiency.Endothelial tip cell outgrowth of blood-vessel sprouts marks the initiation of angiogenesis which is critical in physiological and pathophysiological procedures. However, how mechanical characteristics of extracellular matrix (ECM) modulates tip cell formation has been largely neglected. In this study, we found enhanced CD31 expression in the stiffening outer layer of hepatocellular carcinoma than in surrounding soft tissues. Stiffened matrix promoted sprouting from endothelial cell (EC) spheroids and upregulated expressions of tip cell-enriched genes in vitro. Moreover, tip cells showed increased cellular stiffness, more actin cytoskeleton organization and enhanced YAP nuclear transfer than stalk and phalanx ECs. We further uncovered that substrate stiffness regulates FAK and Paxillin phosphorylation in focal adhesion of ECs promoting Rac1 transition from inactive to active state. YAP is subsequently activated and translocated into nucleus, leading to increased tip cell specification. Hedgehog antagonist p-Paxillin can also loosen the intercellular connection which also facilitates tip cell specification. Collectively our present study shows that matrix stiffness modulates tip cell formation through p-PXN-Rac1-YAP signaling axis, shedding light on the role of mechanotransduction in tip cell formation. This is of special significance in biomaterial design and treatment of some pathological situations.Thanks to their biocompatibility, biodegradability, injectability and self-setting properties, calcium phosphate cements (CPCs) have been the most economical and effective biomaterials of choice for use as bone void fillers. They have also been extensively used as drug delivery carriers owing to their ability to provide for a steady release of various organic molecules aiding the regeneration of defective bone, including primarily antibiotics and growth factors. This review provides a systematic compilation of studies that reported on the controlled release of drugs from CPCs in the last 25 years. The chemical, compositional and microstructural characteristics of these systems through which the control of the release rates and mechanisms could be achieved have been discussed. In doing so, the effects of (i) the chemistry of the matrix, (ii) porosity, (iii) additives, (iv) drug types, (v) drug concentrations, (vi) drug loading methods and (vii) release media have been distinguished and discussed individually. Kinetic specificities of in vivo release of drugs from CPCs have been reviewed, too. Understanding the kinetic and mechanistic correlations between the CPC properties and the drug release is a prerequisite for the design of bone void fillers with drug release profiles precisely tailored to the application area and the clinical picture. The goal of this review has been to shed light on these fundamental correlations.The treatment of malignant bone tumors by chemotherapeutics often receives poor therapeutic response due to the specific physiological bone environment, and thus calls for the development of new therapeutic options. Here, we reported a bone-targeted protein nanomedicine for this purpose. Saporin, a toxin protein, was co-assembled with a boronated polymer for intracellular protein delivery, and the formed nanoparticles were further coated with an anionic polymer poly (aspartic acid) to shield the positive charges on nanoparticles and provide the bone targeting function. The prepared ternary complex nanoparticles showed high bone accumulation both in vitro and in vivo, and could reverse the surface charge property from negative to positive after locating at tumor site triggered by tumor extracellular acidity. The boronated polymer in the de-shielded nanoparticles further promote intracellular delivery of saporin into tumor cells, exerting the anticancer activity of saporin by inactivation of ribosomes. As a result, the bone-targeted and saporin-loaded nanomedicine could kill cancer cells at a low saporin dose, and efficiently prevented the progression of osteosarcoma xenograft tumors and bone metastatic breast cancer in vivo. This study provides a facile and promising strategy to develop protein-based nanomedicines for the treatment of malignant bone tumors.Formation of graded biomaterials to render shape-morphing scaffolds for 4D biofabrication holds great promise in fabrication of complex structures and the recapitulation of critical dynamics for tissue/organ regeneration. Here we describe a facile generation of an adjustable and robust gradient using a single- or multi-material one-step fabrication strategy for 4D biofabrication. By simply photocrosslinking a mixed solution of a photocrosslinkable polymer macromer, photoinitiator (PI), UV absorber and live cells, a cell-laden gradient hydrogel with pre-programmable deformation can be generated. Gradient formation was demonstrated in various polymers including poly(ethylene glycol) (PEG), alginate, and gelatin derivatives using various UV absorbers that present overlap in UV spectrum with that of the PI UV absorbance spectrum. Moreover, this simple and effective method was used as a universal platform to integrate with other hydrogel-engineering techniques such as photomask-aided microfabrication, photo-patterning, ion-transfer printing, and 3D bioprinting to fabricate more advanced cell-laden scaffold structures. Lastly, proof-of-concept 4D tissue engineering was demonstrated in a study of 4D bone-like tissue formation. The strategy's simplicity along with its versatility paves a new way in solving the hurdle of achieving temporal shape changes in cell-laden single-component hydrogel scaffolds and may expedite the development of 4D biofabricated constructs for biological applications.Therapeutic oligonucleotides (TOs) represent one of the most promising drug candidates in the targeted cancer treatment due to their high specificity and capability of modulating cellular pathways that are not readily druggable. However, efficiently delivering of TOs to cancer cellular targets is still the biggest challenge in promoting their clinical translations. Emerging as a significant drug delivery vector, nanoparticles (NPs) can not only protect TOs from nuclease degradation and enhance their tumor accumulation, but also can improve the cell uptake efficiency of TOs as well as the following endosomal escape to increase the therapeutic index. Furthermore, targeted and on-demand drug release of TOs can also be approached to minimize the risk of toxicity towards normal tissues using stimuli-responsive NPs. In the past decades, remarkable progresses have been made on the TOs delivery based on various NPs with specific purposes. In this review, we will first give a brief introduction on the basis of TOs as well as the action mechanisms of several typical TOs, and then describe the obstacles that prevent the clinical translation of TOs, followed by a comprehensive overview of the recent progresses on TOs delivery based on several various types of nanocarriers containing lipid-based nanoparticles, polymeric nanoparticles, gold nanoparticles, porous nanoparticles, DNA/RNA nanoassembly, extracellular vesicles, and imaging-guided drug delivery nanoparticles.The pathophysiology of dilated cardiomyopathy (DCM), one major cause of heart failure, is characterized by the dilation of the heart but remains poorly understood because of the lack of adequate in vitro models. Current 2D models do not allow for the 3D organotypic organization of cardiomyocytes and do not reproduce the ECM perturbations. In this review, the different strategies to mimic the chemical, physical and topographical properties of the cardiac tissue affected by DCM are presented. The advantages and drawbacks of techniques generating anisotropy required for the cardiomyocytes alignment are discussed. In addition, the different methods creating macroporosity and favoring organotypic organization are compared. Besides, the advances in the induced pluripotent stem cells technology to generate cardiac cells from healthy or DCM patients will be described. Thanks to the biomaterial design, some features of the DCM extracellular matrix such as stiffness, porosity, topography or chemical changes can impact the cardiomyocytes function in vitro and increase their maturation. By mimicking the affected heart, both at the cellular and at the tissue level, 3D models will enable a better understanding of the pathology and favor the discovery of novel therapies.The real physiological environment of human body is complicated with different degrees and forms of dynamic loads applied to implanted medical devices due to the daily activities of the patients, which would have impacts on the degradation behaviors of magnesium alloy implants. In this work, the bio-corrosion behaviors of AZ31B magnesium alloy under alternating cyclic dynamic loads with different low frequencies (0.1-2.5 Hz) were specially investigated. It was found that the bio-degradation performances under external dynamic stressed conditions were much severer than those under unstressed conditions and static loads. The corrosion rates were generally accelerated as the rise of cyclic frequency. Hereby a numerical model for the degradation process of Mg alloy was established. The corrosion current density i corr of Mg alloy and the applied loading frequency f matches a linear relationship of ln i corr ∝ f, which is the result of interactions between the cyclic alternating load and corrosive environment. This work could provide a theoretical reference and an experimental basis for further researches on the biodegradation behaviors of biomedical materials under dynamic conditions.