Macromolecular bioscience最新文献

Antimicrobial resistance is a major global health challenge, and the current gold standards for antibiotic susceptibility testing typically require 16–48 h. This study reports bacterial cellulose-based devices for rapid colorimetric antimicrobial susceptibility profiling using two laboratory strains, E. coli DH5-α and Staphylococcus aureus. The freeze-dried bacterial cellulose substrate, with its nanofibrous structure and high porosity, is evaluated for its ability to accommodate bacterial inoculum, antibiotic, and a halochromic dye. Structural analyses show improved moisture retention compared to filter paper, which tends to dry rapidly. Using this platform, susceptibility to ampicillin and resistance to nalidixic acid become visually distinguishable within a single doubling time. An unsupervised K-means clustering algorithm is employed to segment colorimetric outputs and quantify viability-driven changes in the assay. This study presents freeze-dried bacterial cellulose devices that provide a clear visual distinction between susceptibility and resistance within a single bacterial doubling time.

Acute lung injury (ALI) is a common respiratory disease accompanied by alveolar capillary membrane dysfunction, inflammation and alveolar fluid deposition. Currently, the primary treatment for ALI involves intravenous or oral administration of glucocorticoid drugs. However, this approach suffers from low effective drug concentrations reaching the lungs and may cause systemic toxic side effects. Therefore, there is an urgent need to develop novel therapeutic agents and optimized delivery strategies specifically tailored for ALI treatment. On one hand, pravastatin (Prv) exhibits potent anti-inflammatory and antioxidant properties and has demonstrated therapeutic efficacy in ALI treatment, positioning it as a promising drug candidate. However, its underlying mechanisms remain poorly understood. On the other hand, inhalation represents a highly promising delivery approach for ALI therapy by enhancing drug retention in the lungs. Nevertheless, this localized administration strategy still faces the challenge of mucus barrier impeding drug penetration. Herein, a ferritin-based pravastatin nanoassembly (Prv@FTn) was developed to improve the mucus-penetrating ability of Prv. In vitro and in vivo investigations revealed that Prv@FTn alleviates LPS-induced ALI symptoms through inhibition of the Rho-ROCK I/II signaling pathway. These findings suggest that mucus-penetrating Prv@FTn is a promising Rho/ROCK signaling pathway inhibitor for ALI therapy.

Vascular Endothelial Growth Factor (VEGF) is a critical factor in pathological neovascularization, making it the primary target for ocular anti-angiogenic therapies. Anti-VEGF treatments suffer from requiring frequent intraocular injections for effective treatment due to limited half-life. This study aimed to utilize a composite nanoparticle-hydrogel drug delivery system consisting of poly(glycerol sebacate) (PGS) nanoparticles and cross-linked hyaluronic acid hydrogel to achieve an extended release of anti-VEGF agent, HRH peptide, with the objective of reducing the frequency of intravitreal injections required for treatment of neovascular diseases. Our findings reveal a promising 42.54% ± 5.99% drug release from HA-PGS NP@HRH within the first 3 months, indicating potential for sustained drug release applications. Cell viability studies demonstrate biocompatibility with human retinal pigment epithelium (ARPE-19) cells and reveal anti-angiogenic effects by binding to VEGF receptors on human umbilical vein endothelial (HUVEC) cells, inhibiting VEGF activity, cell growth (with 55.19% cell viability), and tube formation of HUVECs. In vivo experiments with an oxygen-induced retinopathy (OIR) model demonstrated a suppression of neovascularization in mice treated with PGS NPs@HRH. Our research strives to contribute to the development of these new-generation materials, promising improved treatment efficacy and ultimately enhancing the quality of life for patients affected by these challenging conditions.

Thrombotic disorders rank among the principal global mortality factors. Despite significant advancements in interventional therapy technologies, conventional medical robots remain constrained by rigid architectures and elevated invasiveness, leading to vascular wall stress and frictional injury. Furthermore, these systems face challenges in reconciling the flexibility necessary for untethered navigation with reliable vascular traversal. To overcome these limitations, we present a magnetically actuated Micro-transformers (MAMT) with in situ structural reconfigurability. The microrobot, constructed from shape memory polymer (SMP), leverages the magnetothermal effect of Fe₃O₄ magnetic nanoparticles induced by an alternating magnetic field (AMF). When the temperature surpasses the glass transition temperature (50°C) of the SMP, the robot's structure transitions from its initial rod-like form to a final helical shape. Thus, dual-mode operation is achieved: rod-shaped structures for navigation and spiral-shaped structures for thrombus fragmentation. In the MAMT fabricated in this paper, in a simulated blood environment at room temperature, structural switching could be completed within 148 ± 8 s with AMF, and its shape recovery ratio could reach 92.11%. In the simulated thrombus clearance experiments, the thrombus clearance ratio could reach 52.7%. It can reduce the risk of vascular wall injury and enhance the safety of thrombus removal, offering an innovative solution for thrombus treatment.

Bioprinting technologies face challenges in designing bioinks that possess optimal pre- and post-bioprinting properties. In most cases, enhancing flowability to improve pre-bioprinting properties results in inferior mechanical properties of the post-printed constructs. To achieve adequate mechanical strength, physical or chemical cross-linking is used, which compromises the biocompatibility and degradability of the constructs. A xanthan gum (XG) and tamarind seed polysaccharide (TSP) blend bioink was developed to overcome these limitations. Amongst several ratios, 4XG:1TSP (4X1T) demonstrated the highest printability with accuracy >95%. Rheological investigations revealed shear thinning viscosity while the LVER and creep recovery for 4X1T (698 MPa, 97%) and 4X (624 MPa, 85%) showed suitable properties for bioprinting applications. FTIR indicated hydrogen-bonding interactions between XG and TSP, conferring structural stability to the post-printed constructs without any crosslinking agent. The constructs showed loss of microstructure after 21 days of incubation in phosphate buffer (pH 7.5) at 37°C. In vitro cytocompatibility studies with human-derived SH-SY5Y cells disclosed no significant difference between the viability of cells seeded on XG and 4X1T, or cells bioprinted with 4X1T bioinks. It is concluded that the XG-TSP blend provides a bioink with promising printability, mechanical integrity, degradability, and cytocompatibility for the fabrication of tissue engineering constructs.

Transdermal peptides, Engineered from bioactive peptides through rational sequence modification and structural optimization, transdermal peptides have emerged as a transformative strategy for enhancing the transdermal delivery of macromolecular drugs, proteins, and nucleic acids. This review outlines the structural classifications of bioactive peptides, including short, linear, cyclic, cationic, anionic, and neutral peptides, as well as their diverse biological sources. It focuses on the design principles and penetration mechanisms of transdermal peptides. These peptides interact dynamically with skin constituents, such as lipids and keratins, by fine-tuning the hydrophilic-hydrophobic balance, molecular weight, and conformational stability. This transiently disrupts the stratum corneum barrier and facilitates drug permeation via endocytosis and receptor-mediated pathways. They find applications in various pharmaceutical domains, including localized anticancer and antimicrobial therapies, as well as in cosmetics for whitening, anti-aging, and moisturizing. They are also being explored in innovative areas such as hair regeneration and wound healing. When combined with advanced delivery platforms, such as nanocarriers, microneedles, and microfluidic systems, transdermal peptides can significantly improve targeting efficacy and enable controlled release. Despite challenges related to peptide immunogenicity and scalable synthesis, the future integration of smart, stimuli-responsive technologies and artificial intelligence promises to Bioactive peptides, Skin permeation mechanisms, Skin transmission, Transdermal peptidesadvance personalized transdermal therapeutics.

Current treatments for critical-sized bone defects are often ineffective, necessitating advanced biomaterial scaffolds that can address this limitation. A key challenge in developing these scaffolds is achieving sustained, localized delivery of osteoinductive drugs, which is crucial for enhancing bone tissue regeneration within the defect site. This research engineered a novel κ-carrageenan-based composite scaffold incorporating hydroxyapatite-coated chitosan nanoparticles for regulated rosuvastatin release. Chitosan nanoparticles containing rosuvastatin were synthesized using a water-in-oil emulsion method and subsequently coated with hydroxyapatite. κ-carrageenan-based scaffolds were then fabricated with varying concentrations of nanoparticles (0%, 10%, 20%, and 30%) and evaluated for their physical and mechanical properties. They were also assessed for biocompatibility, osteogenic differentiation potential, and hemocompatibility. Notably, the hydroxyapatite coating increased the size of nanoparticles and enabled a stable, long-term release of rosuvastatin. Moreover, incorporating these nanoparticles into scaffolds further enhanced the sustained release profile appropriate for long-term bone healing. Scaffolds containing 20% nanoparticles demonstrated the highest mechanical strength and were selected for cell adhesion, proliferation, and differentiation studies. Alkaline phosphatase activity and alizarin red staining confirmed the scaffolds’ ability to promote osteogenic differentiation. Hemocompatibility assessment revealed a low hemolysis percentage (< 5%) for the carrageenan-based scaffolds, indicating good blood compatibility. Overall, the developed composite scaffold exhibits promising biocompatibility and efficacy for the controlled delivery of rosuvastatin and the repair of bone defects.

Polydeoxyribonucleotide (PDRN), a bioactive DNA fragment, has been known to promote anti-inflammatory responses and wound healing primarily via adenosine A₂A receptor activation. However, low molecular weight PDRN can undergo rapid degradation, limiting its sustained therapeutic efficacy. In this study, we developed a scalable method to produce high-purity, and low molecular weight PDRN (c.a. 325 bp) from calf thymus DNA via physical fragmentation. To enhance its stability and delivery, PDRN was encapsulated in poly(lactic-co-glycolic acid) (PLGA) to form PDRN/PLGA nanoparticles, yielding uniform and spherical particles (336 ± 43 nm). These nanoparticles exhibited excellent colloidal stability and biodegradability (38.3% over 14 days), with sustained PDRN release (88.39% over 14 days). Moreover, the nanoformulation effectively protected PDRN from thermal, acidic, enzymatic, and UV degradation. The PDRN/PLGA nanoparticles, which exhibited no cytotoxicity or hemolysis, demonstrated superior anti-inflammatory and wound-healing efficacy compared to free PDRN. In an in vitro lipopolysaccharide (LPS)-induced inflammatory wound model, they significantly accelerated wound closure compared to both LPS-treated and untreated controls. These results suggest that nanoformulation effectively protects low molecular weight PDRN, thereby significantly enhancing its therapeutic activity and underscore the potential of PDRN/PLGA nanoparticles as a stable and effective platform for the regeneration of skin inflammation.