Smart medicine最新文献

Liver tissue engineering offers potential in liver transplantation, while the development of hydrogels for scalable scaffolds incorporating natural components and effective functionalities is ongoing. Here, we propose a novel microfluidic 3D printing hydrogel derived from decellularized fish liver extracellular matrix for liver regeneration. By decellularizing fish liver and combining it with gelatin methacryloyl, the hydrogel scaffold retains essential endogenous growth factors such as collagen and glycosaminoglycans. Additionally, microfluidic-assisted 3D printing technology enables precise modulation of the composition and architecture of hydrogels to fulfill clinical requirements. Benefiting from the natural source of materials, the hydrogels exhibit excellent biocompatibility and cellular proliferation capacity for incorporating induced pluripotent stem cell-derived hepatocytes (iPSC-heps). Furthermore, the macroscopic architecture and biomechanical environment of hydrogels foster optimal functional expression of iPSC-heps. Importantly, post-transplantation, the hydrogels significantly enhance survival rates and liver function in mice with acute liver failure, promoting liver regeneration and repair. These findings suggest that microfluidic 3D printed hydrogels represent promising candidates for liver transplantation and functional recovery.

Phospholipid-based liposomes are among the most successful nanodrug delivery systems in clinical use. However, these conventional liposomes present significant challenges including low drug-loading capacity and issues with drug leakage. Drug-phospholipid conjugates (DPCs) and their assemblies offer a promising strategy for addressing these limitations. In this review, we summarize recent advances in the design, synthesis, and application of DPCs for drug delivery. We begin by discussing the chemical backbone structures and various design strategies such as phosphate head embedding and mono-/bis-embedding in the sn-1/sn-2 positions. Furthermore, we highlight stimulus-responsive designs of DPCs and their applications in treating diseases such as cancer, inflammation, and malaria. Lastly, we explore future directions for DPCs development and their potential applications in drug delivery.

Atherosclerosis (AS) is a major cause of cardiovascular disease. In particular, the unpredictable rupture of vulnerable atherosclerotic plaques (VASPs) can cause serious cardiovascular events such as myocardial infarction, stroke, and even sudden death. Therefore, early evaluation of the vulnerability of atherosclerotic plaques is of great importance. However, clinical imaging techniques are only marginally useful in the presence of severe anatomical structural changes, making it difficult to evaluate plaque vulnerability at an early stage. With the development of molecular imaging and nanotechnology, specific nanoprobes constructed for the pathological features of VASPs have attracted much attention for their ability to visualize VASPs early and noninvasively at the cellular and molecular levels. Here, we outline the pathological features of VASPs, analyze the superiority and limitations of current clinical imaging techniques, introduce the rational design principles of nanoprobes, and systematically summarize the application of nanoprobes to visualize the features of VASPs at the cellular and molecular levels. In addition, we discussed the prospects and urgent challenges in this field, and we believe it will provide new ideas for the early and accurate diagnosis of cardiovascular diseases.

Chondrocytes are commonly applied in regenerative medicine and tissue engineering. Thus, the discovery of optimal culture conditions to obtain cells with good properties and behavior for transplantation is important. In addition to biochemical cues, physical and biomechanical changes can affect the proliferation and protein expression of chondrocytes. Here we investigated the effect of extracellular matrix stiffness on mouse articular chondrocyte phenotype, growth, and subcellular p53 localization. Chondrocytes were seeded on collagen-coated substrates varying in elasticity: 0.5 and 100 kPa. Immunocytochemical staining and immunoblotting showed that a softer substrate significantly increased p53 nuclear localization in chondrocytes. Furthermore, we identified microRNA-532 (miR-532) as a potential p53 target gene to influence cell function, indicating a new target for tissue engineering. These findings provide insight into the influence of physical cues on cell phenotype maintenance and could help improve understanding of cartilage-related pathologies such as osteoarthritis.

Bioorthogonal chemistry, recognized as a highly efficient tool in chemical biology, has shown significant value in cancer treatment. The primary objective is to develop efficient delivery strategies to achieve enhanced bioorthogonal drug treatment for tumors. Here, Janus microparticles (JMs) loaded with cyclooctene-modified doxorubicin prodrug (TCO-DOX) and tetrazine-modified indocyanine green (Tz-ICG) triggers are reported. Besides activating TCO-DOX, Tz-ICG is also a photothermal agent used in photothermal therapy (PTT), enabling the simultaneous use of biorthogonal chemotherapy and PTT. Additionally, the DOX could be significantly reduced in systemic toxicity with the modification of cyclooctene. Thus, the developed drug-carrying JMs system exhibits effective tumor cell killing in vitro and effectively inhibits tumor local progress and distant lung metastasis after postoperative treatment with good safety. These results demonstrate that the prepared JMs provide a paradigm for bioorthogonal prodrug activation and localized delivery, and hold great promise for cancer therapy as well as other related applications.

Vertigo is a common symptom of various diseases that affects a large number of people worldwide. Current leading treatments for intractable peripheral vertigo are to intratympanically inject ototoxic drugs such as gentamicin to attenuate the semicircular canal function but inevitably cause hearing injury. Photodynamic therapy (PDT) is a noninvasive therapeutic approach by precisely targeting the diseased tissue. Here, we developed a PDT-based method for treating intractable peripheral vertigo in a mouse model using a polymer-coated photosensitizer chlorin e6 excited by red light. We found that a high dose of PDT attenuated the function of both semicircular canals and otolith organs and damaged their hair cells. Conversely, the PDT exerted no effect on hearing function or cochlear hair-cell viability. These results suggest the therapeutic potential of PDT for treating intractable peripheral vertigo without hurting hearing. Besides, the attenuation level and affected area can be precisely controlled by adjusting the light exposure time. Furthermore, we demonstrated the potential of this therapeutic approach to be minimally invasive with light irradiation through bone results. Thus, our PDT-based approach for attenuating the function of the semicircular canals offers a basis for developing a less-invasive and targeted therapeutic option for treating vertigo.

Silk fibroin (SF)-based hydrogels are promising multifunctional adhesive candidates for real-world applications in tissue engineering, implantable bioelectronics, artificial muscles, and artificial skin. However, developing conductive SF-based hydrogels that are suitable for the micro-physiological environment and maintain their physical and chemical properties over long periods of use remains challenging. Herein, we developed an ion-conductive SF hydrogel composed of glycidyl methacrylate silk fibroin (SilMA) and bioionic liquid choline acylate (ChoA) polymer chains, together with the modification of acrylated thymine (ThyA) and adenine (AdeA) functional groups. The resulting polymeric ion-conductive SF composite hydrogel demonstrated high bioactivity, strong adhesion strength, good mechanical compliance, and stretchability. The formed hydrogel network of ChoA chains can coordinate with the ionic strength in the micro-physiological environment while maintaining the adaptive coefficient of expansion and stable mechanical properties. These features help to form a stable ion-conducting channel for the hydrogel. Additionally, the hydrogel network modified with AdeA and ThyA, can provide a strong adhesion to the surface of a variety of substrates, including wet tissue through abundant hydrogen bonding. The biocompatible and ionic conductive SF composite hydrogels can be easily prepared and incorporated into flexible skin or epidermal sensing devices. Therefore, our polymeric SF-based hydrogel has great potential and wide application to be an important component of many flexible electronic devices for personalized healthcare.

Peptide spectrum matching is the process of linking mass spectrometry data with peptide sequences. An experimental spectrum can match thousands of candidate peptides with variable modifications leading to an exponential increase in candidates. Completing the search within a limited time is a key challenge. Traditional searches expedite the process by restricting peptide mass errors and variable modifications, but this limits interpretive capability. To address this challenge, we propose Dear-PSM, a peptide search engine that supports full database searching. Dear-PSM does not restrict peptide mass errors, matching each spectrum to all peptides in the database and increasing the number of variable modifications per peptide from the conventional 3-20. Leveraging inverted index technology, Dear-PSM creates a high-performance index table of experimental spectra and utilizes deep learning algorithms for peptide validation. Through these techniques, Dear-PSM achieves a speed breakthrough 7 times faster than mainstream search engines on a regular desktop computer, with a remarkable 240-fold reduction in memory consumption. Benchmark test results demonstrate that Dear-PSM, in full database search mode, can reproduce over 90% of the results obtained by mainstream search engines when handling complex mass spectrometry data collected from different species using various instruments. Furthermore, it uncovers a substantial number of new peptides and proteins. Dear-PSM has been publicly released on the GitHub repository https://github.com/jianweishuai/Dear-PSM.