Journal of materials chemistry. B最新文献

Chronic nonhealing wounds represent significant complications of diabetes, bearing a substantial burden and posing risks of disability or mortality. In diabetic wounds, continuous tissue fluid exudation, inflammatory cell migration, fibrosis, and bacterial biofilm formation create a "barrier", which decreases the treating efficacy of therapeutics. To address these limitations, a recombinant human collagen type III microneedle patch (rhCol III-PRP^M) loaded with platelet-rich plasma (PRP) was developed, in which methacrylated rhCol III (rhCol III-MA) loaded with PRP was utilized to form needle tips, while rhCol III-MA formed the base part of the patch. RhCol III-PRP^M featured adequate mechanical qualities, swelling capacity, and sustained in vitro release of growth factors from the activation of PRP for over 7 days. Leveraging the synergistic effects of rhCol III and PRP, rhCol III-PRP^M patches facilitated cell proliferation, migration, and angiogenesis, and reduced oxidative stress. In animal experiments, this microneedle patch effectively promoted the healing of diabetic wounds during a 20-day treatment, partially due to upregulating integrins and phosphorylated ERK protein levels. Diverging from other microneedle strategies, the rhCol III exhibited "dual functionality," serving as both the microneedle patch matrix and therapeutic agent, promoting wound healing upon patch dissolution while delivering PRP. The combination of rhCol III and PRP in the form of a microneedle patch offered a straightforward and efficacious way for effective diabetic wound management, and showed promise in bringing new possibilities in clinical practice.

Cartilage injury represents a significant clinical challenge, necessitating innovative repair strategies. Self-healing injectable hydrogels are emerging as promising solutions for cartilage regeneration. However, the hydrogel with robust mechanical strength mimicking the natural cartilage and appropriate extracellular matrix production has not yet been achieved. To address this challenge, we have fabricated self-healing injectable hydrogels by combining oxidized alginate (OA) and gelatin (G) with recombinant hyaluronic acid (HA) of varying molecular weights (0.5 MDa, 1.0 MDa, and 2.0 MDa) derived from metabolically engineered Lactococcus lactis. Incorporating HA resulted in improved physicochemical, mechanical, and biological properties. The 1.0 MDa HA-incorporated hydrogel (OAGH_1.0) exhibited superior injectability and self-healing efficiency due to the balance between dynamic covalent and non-covalent interactions within the hydrogel network. The OAGH_1.0 hydrogel's enhanced shear-thinning properties aided in printing the hydrogel into a mesh-like structure using a 3D printer. The OAGH_1.0 hydrogel showed an ultimate strength of 1.2 MPa, comparable to the natural cartilage. In vitro studies confirmed that these hydrogels also fostered cell adhesion, proliferation, and collagen deposition. These results indicate that the balance between dynamic covalent and non-covalent interactions achieved in the OAGH_1.0 hydrogel will open promising avenues for advancing cartilage regeneration.

The development of theranostic systems is of fundamental importance for the treatment of diseases. These systems should combine the features of fluorescent molecules that can act as diagnostic systems and species with therapeutic potential. Herein, we report the synthesis of a multifunctional halloysite nanotube (HNT)-based nanomaterial via the covalent modification of the external surface of the clay with a halochromic probe and the immobilization of Fe₃O₄ nanoparticles (HNTs-1@Fe₃O₄) with chemodynamic activity. The covalent modification of HNTs was performed using two different synthetic approaches, and the best strategy was evaluated by estimating the degree of functionalization of the clay via thermogravimetric analysis. The synthesized nanomaterial was thoroughly characterized, and its photoluminescence properties under different conditions, i.e. different solvents, pH conditions and temperatures, were studied. The HNTs-1@Fe₃O₄ nanomaterial was found to exhibit good peroxidase-like activity, as shown by testing its performance in the catalytic oxidation of the colorless enzyme substrate 3,3',5,5'-tetramethylbenzidine (TMB) to blue TMB oxide (ox-TMB) in the presence of H₂O₂. This study highlights the usefulness of the covalent approach for modifying halloysite surfaces to generate nanomaterials for potential tissue imaging under different stimuli. In addition, the combination with Fe₃O₄NPs led to the synthesis of multifunctional materials with potential use as theranostic systems for the treatment of diseases.

Micro/nanofibrous materials play an increasingly important role in tissue regeneration due to their ECM-mimicking properties and mechanical regulation capabilities. This study developed a microfiber fabrication method based on molten stringing of fused deposition modeling (FDM), successfully creating an ordered microfiber network with spatial structures. It surpasses the size limits of FDM filaments, enabling the precise fabrication of microfibers with diameters of 15-150 μm. The customizable PLA microfiberous-net was then encapsulated in GelMA hydrogel and mineralized in situ, effectively producing biomimetic bone repair materials with customization of surface microstructures and control of micromechanics, which in turn influences and regulates cell behavior. By adjusting the structure and density of the microfiber network, it is possible to control the compressive modulus, viscoelasticity, and tensile strength to match the micromechanical environment for cell spreading and proliferation. Additionally, the network structure can guide cell alignment and aggregation, influencing cell morphology and enabling controlled guidance of cellular behavior. Our simple and convenient microfibrous printing method holds great potential for the preparation of various fibrous materials for tissue regeneration.

Thanks to their considerable toughness, self-recoverability, high swelling degree and stimuli-responsiveness, hydrophobic association (HA) hydrogels are promising in wearable electronics, biomedical applications and the water treatment industry. Multiple (physical and/or chemical) cross-links can also promote the above-mentioned properties, broadening the applications of the gels. Previous reviews on the HA hydrogels focused only on their mechanical and self-healing properties for biomedical applications. Herein, we aim to introduce HA hydrogels having multiple crosslinks (multi-cross-linked HA (MCHA) gels), discuss their various properties, and then present their (potential) practical applications. To explain, this review first describes the synthesis of MCHA gels. Then, the mechanical, rheological, self-healing, injectability, swelling, and stimuli-responsive properties of MCHA hydrogels are discussed. In the meantime, we suggest useful approaches to address the current challenges for the sake of improving these properties. Finally, based on the properties of MCHA gels, we introduce their (potential) applications in the fields of soft electronics, biomedicine, the environment, and superabsorbents, followed by evaluation of the performance of the developed devices in some cases. Taken together, this review can provide helpful perspectives for developing high-performance MCHA hydrogels.

Photodynamic therapy (PDT) is a promising cancer treatment that relies on reactive oxygen species (ROS) to disrupt cellular redox homeostasis, ultimately leading to cell death. The thioredoxin (Trx) system is a pivotal regulatory system for antioxidant defence, which plays a key role in immune response and cell death. Thus, perturbating the Trx system could enhance the efficacy of PDT. Naphthalimide skeletons are research hotspots in photosensitizers due to their tunable photophysical properties and high ROS yield. A series of novel photosensitizers based on naphthalimide skeletons were designed and synthesized here. Photocytotoxicity assays demonstrated that most compounds possessed considerable photosensitive effects, and DPA-NI-Bu exhibited the highest photocytotoxicity (phototoxicity index > 66.23) with IC₅₀ values of 1.51 ± 0.32 μM upon light activation. Mechanistic studies revealed that DPA-NI-Bu significantly disrupts intracellular redox homeostasis by disrupting the Trx system and glutathione (GSH) system, thereby promoting apoptosis. Furthermore, clone formation assays showed that DPA-NI-Bu exerted a potent photodynamic effect, inhibiting tumor cell proliferation by 94.9 ± 2.8%. These findings highlight the significant improvement in photosensitizing properties through structural modification and offer valuable insights for designing more effective photosensitizers for PDT applications.

Abundant adenosine triphosphate (ATP), an important mediator of metabolic reprogramming in cancer progression, is regarded as a significant target in cancer treatment. Nonetheless, due to low selectivity, attempts to exhaust ATP may induce undesirable side effects because ATP also plays key roles in maintaining normal cell function. Inspired by the feedback inhibition mechanism found in nature, we propose feedback inhibition of the mitochondrial ATP synthetic pathway for tumor inhibition with minimal side effects. As a proof-of-concept, an ATP-responsive ZIF-90 broad framework for the mitochondria-targeted delivery of 2,2'-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH) and an FDA-approved drug, bedaquiline (BE), is presented in this work. The ZIF-90/AIPH/BE nanocomplex exhibits unique properties, including high pulmonary accumulation and mitochondria-targeting capability. When ATP is present, the ZIF-90/AIPH/BE nanoparticles disintegrate and release the encapsulated molecules because of the competitive binding between ATP and Zn²⁺ present in ZIF-90. The released AIPH and BE significantly reduce ATP production, causing mitochondrial ATP depletion. The reduction in ATP acts as a negative feedback and restricts the subsequent release of the ZIF-90/AIPH/BE nanocomplex. The feedback inhibition mechanism expands the possibility of targeted disease treatment and opens up new avenues for ATP-based nanomedicine.

H₂O₂ plays a significant role in tumor development. However, tumor cells possess certain protective mechanisms that reduce the cytotoxic effects of H₂O₂. Researchers have observed a notable increase in the expression of hyaluronic acid (HA), which possesses antioxidant properties, within the tumor microenvironment. This investigation revealed that HA can mitigate oxidative damage to tumors. In response to exogenous H₂O₂, tumor cells enhance their production of HA as a mechanism to counteract external oxidative stress. The suppression of HA levels through hyaluronidase or ribavirin significantly heightened the cytotoxic effects of H₂O₂ and led to an accumulation of intracellular reactive oxygen species (ROS), ultimately inhibiting tumor cell proliferation. A formulation known as H₂O₂@Lip + Rib@Lip was developed, utilizing liposomes encapsulated with H₂O₂ and ribavirin, and was tested in murine models. The results indicated a significant reduction in tumor volume in the H₂O₂@Lip + Rib@Lip treatment group compared to the H₂O₂@Lip and Rib@Lip groups. Furthermore, these findings were accompanied by decreased levels of HA and CD44 receptors, increased levels of H₂O₂, and enhanced apoptosis within the tumor tissues. Therefore, in the context of ROS and related therapies, HA should be prioritized as it serves as the primary and rapid antioxidant barrier in cells. Blocking HA metabolism presents a potential strategy for enhancing oxidative stress therapy.

Staphylococcus aureus (S. aureus), a commensal organism found on the human skin, is commonly associated with nosocomial infections and exhibits virulence mediated by toxins and resistance to antibiotics. The global threat of antibiotic resistance has necessitated antimicrobial stewardship to improve the safe and appropriate use of antimicrobials; hence, there is an urgent demand for the advanced, cost-effective, and rapid detection of specific bacteria. In this regard, we aimed to selectively detect S. aureus using surface molecularly imprinted magnetic nanoparticles templated with a well-known biomarker protein A, specific to S. aureus. Herein, a highly selective surface molecularly imprinted polymeric thin layer was created on ∼250 nm magnetic nanoparticles (MNPs) through the immobilization of protein A to aldehyde functionalized MNPs, followed by monomer polymerization and template washing. This study employs the rational selection of monomers based on their computationally predicted binding affinity to protein A at multiple surface residues. The resulting MIPs from rationally selected monomer combinations demonstrated an imprinting factor as high as ∼5. Selectivity studies revealed MIPs with four-fold higher binding capacity (BC) to protein A than other non-target proteins, such as lysozyme and serum albumin. In addition, it showed significant binding to S. aureus, whereas negligible binding to other non-specific Gram-negative, i.e. Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), and Gram-positive, i.e. Bacillus subtilis (B. subtilis), bacteria. This MIP was employed for the capture and specific detection of fluorescently labeled S. aureus. Quantitative detection was performed using a conventional plate counting technique in a linear detection range of 10¹-10⁷ bacterial cells. Remarkably, the MIPs also exhibited approximately 100% cell recovery from milk samples spiked with S. aureus (10⁶ CFU mL^-1), underscoring its potential as a robust tool for sensitive and accurate bacterial detection in dairy products. The developed MIP exhibiting high affinity and selective binding to protein A finds its potential applications in the magnetic capture and selective detection of protein A as well as S. aureus infections and contaminations.

Lipid nanoparticles (LNPs) are commonly employed for drug delivery owing to their considerable drug-loading capacity, low toxicity, and excellent biocompatibility. Nevertheless, the formation of protein corona (PC) on their surfaces significantly influences the drug's in vivo fate (such as absorption, distribution, metabolism, and elimination) upon administration. PC denotes the phenomenon wherein one or multiple strata of proteins adhere to the external interface of nanoparticles (NPs) or microparticles within the biological milieu, encompassing ex vivo fluids (e.g., serum-containing culture media) and in vivo fluids (such as blood and tissue fluids). Hence, it is essential to claim the PC formation behaviors and mechanisms on the surface of LNPs. This overview provided a comprehensive examination of crucial aspects related to such issues, encompassing time evolution, controllability, and their subsequent impacts on LNPs. Classical studies of PC generation on the surface of LNPs were additionally integrated, and its decisive role in shaping the in vivo fate of LNPs was explored. The mechanisms underlying PC formation, including the adsorption theory and alteration theory, were introduced to delve into the formation process. Subsequently, the existing experimental outcomes were synthesized to offer insights into the research and application facets of PC, and it was concluded that the manipulation of PC held substantial promise in the realm of targeted delivery.