Macromolecular bioscience最新文献

Islet transplantation in type 1 diabetes confronts challenges, including isolation-induced islet damage, hypoxia, re-emergence of autoimmunity, and foreign body reactions. Pre-transplant conditioning strategies that support physiological homeostasis while protecting islets within encapsulation devices are therefore essential. We developed electrospun hydrophilic cellulose acetate (eCA) membranes and hydrophobic polytetrafluoroethylene (ePTFE) membranes with nano-topographical surfaces for islet encapsulation. They were tested for protein adsorption and macrophage activation, while eCA and ePTFE devices were evaluated by encapsulating MIN6 spheroids to assess their encapsulation efficiency and Glucose-stimulated insulin secretion (GSIS) capability. Furthermore, the devices encapsulating MIN6 spheroids were tested for 14 days in a custom 3D-printed bioreactor with continuous dynamic flow. Both eCA and ePTFE membranes restricted the entry or attachment of activated macrophages. The cells encapsulated in eCA-devices released significantly more insulin than those in ePTFE-devices, reflected by higher stimulation indices, suggesting the nutrient transfer ability of eCA. Under dynamic conditions, the encapsulated spheroids in eCA-devices were associated with high viability (80% at day 7 and 98% at day 14) and underwent initial compaction followed by tissue-like structure formation. Microscopy and immunofluorescence revealed the presence of ECM proteins, collagen-1, and E-cadherin, supporting the compaction and remodeling. These results demonstrate that the bioreactor system may be utilised as a pre-transplantation conditioning platform to rehabilitate isolated islets within encapsulated devices.

The appropriate characteristics of carrier biomaterial must prevent rapid sequestration and clearance of exosomes. This study aims to investigate the efficacy of porous phosphate-based glass microspheres (PGMS) as carriers for human dental pulp stem cell (hDPSC)-derived exosomes in dental orthobiologic applications. PGMS (40P₂O₅-24MgO-16CaO-20Na₂O) is prepared via flame spheroidization, characterized using SEM-EDS, XRD, and mercury intrusion porosimetry. hDPSC-Exosomes (Exo) are extracted, labeled with DiL, and verified by confocal and flow cytometry. Cell viability is assessed whereby hDPSCs are exposed to 1 mg/mL PGMS, or 10 µg/mL Exo, or 1 mg/mL PGMS loaded with 10 µg/mL Exo. Osteogenic potential is assessed by ALP assay, qPCR, western blotting, and alizarin staining. PGMS exhibits 75% interconnected pores, and XRD shows broad halo peak within the 2θ range of 20°–40°. Exo are CD9⁺, CD63⁺, and CD81^+, and their cellular uptake is enhanced by 24 h. PGMS supports continued hDPSC proliferation. Exo-alone boosts hDPSC proliferation (24 h) and PGMS+Exo shows a similar rise. Exo-alone and PGMS+Exo significantly upregulate bone markers, while PGMS+Exo significantly upregulates Col1, ALP, and increases nodule formation. Western blotting shows an increase in BMP7, Col1, and OC in Exo-alone and PGMS+Exo. PGMS retains Exo, protects its functionality and release for favorable osteogenesis, offering a promising strategy as an exosome carrier in orthobiologic applications.

Niclosamide (NIC) shows antitumor activity by inhibiting multiple signaling pathways, including signal transducer and activator of transcription 3, Wnt/β-catenin, and NF-κB. However, the poor aqueous solubility and bioavailability limit its potential in treating systemic diseases. To address this, we report here the synthesis of a pH-responsive block copolymer PLLA-b-PDMAEMA-Q based on poly(L-lactide) (PLLA) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) diblock copolymer. First, the PLLA block was prepared by ring-opening polymerization (ROP) followed by the diblock, by atom transfer radical polymerization (ATRP) to prepare PLLA-b-PDMAEMA. Three different block copolymer compositions were synthesized by varying the molecular weight ratio of PLLA to PDMAEMA at 1:2, 1:1, and 1:0.5. PLLA-b-PDMAEMA was then quaternized by reaction with bromoacetic acid to generate PLLA-b-PDMAEMA-Q. In aqueous solution, these copolymers were found to self-assemble into micelles with a hydrodynamic diameter of 79–107 nm. PLLA-b-PDMAEMA-Q was converted to its polyzwitterionic analogue PLLA-b-PDMAEMA-ZIP in PBS buffer (pH 7.4) and used for encapsulation of NIC. The NIC-loaded PLLA-b-PDMAEMA-ZIP (ZIP-NIC) showed a spherical morphology with a hydrodynamic diameter of 230 ± 15.81 nm and significant uptake in HCT116 cells. ZIP-NIC exhibited similar anti-cancer efficacy to free NIC in the HCT116 cell line. Our results suggest that polyzwitterionic nanoparticles constitute a promising class of materials to deliver antitumor drugs and warrant further investigation.

Despite advancements in cancer treatments, lung cancer is one of the most predominant cancer types responsible for a major contribution to cancer-related mortality on a global scale. Folate receptor alpha (FRα) is overexpressed in many epithelial cancers, forming the basis of the “Trojan Horse” strategy in folate-targeting micro/nanoparticles. Using the phytoblend of luteolin and rutin, this study involves the synthesis and optimization of folic acid-functionalized bioactives-loaded chitosan microparticles (FA_CM_loaded) as inhalables. Scanning electron microscopy (SEM) portrays distinctly separated microspheres, while the mass median aerodynamic diameter (MMAD) and hydrodynamic diameter reported ∼3.67 and ∼9.2 µm, respectively. The encapsulation efficiency, drug loading (%), drug release profile, and the Fourier transform infrared spectroscopy (FTIR) confirm the drug-excipient compatibility in the microformulation. The immunomodulatory effect of the treatment protocol is established by the in vitro analysis of the activation of immune cell proliferation, cytokine quantification, and changes in biochemical parameters in cell lines L132 (derived from human embryonic lung tissue) and A549 (adenocarcinomic human alveolar basal epithelial cells). FA_CM_loaded is reported to influence cellular functions without compromising cell viability on L132 and peripheral blood mononuclear cells (PBMCs) till 72 h, but selectively exhibits time-dependent and dose-dependent cytotoxic effect on A549 cells. This study encourages further in vivo validation to establish targeted delivery of flavonoids via the pulmonary route with increased bioavailability and minimal systemic toxicity.

Oral delivery of insulin faces significant challenges due to various barriers present in the gastrointestinal tract, leading to minimal therapeutic outcomes. To overcome these obstacles, chitosan-based nanoparticles modified by L-valine were designed and subsequently coated with fucoidan (FU) to improve the permeation efficiency through the mucus layer and intestinal epithelium. The insulin-loaded nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), encapsulation efficiency (EE), and loading capacity (LC). The prepared nanoparticles VCS-INS-FU NPs, formed by L-valine-grafted chitosan (VCS) and fucoidan, can effectively resist the degradation of insulin by digestive enzymes and exhibit a sustained release profile of encapsulated insulin. Mucoadhesion tests revealed that the nanoparticles VCS-INS-FU NPs (INS/FU 1: 2) had significant mucus permeability. Furthermore, VCS-INS-FU NPs exhibited an enhanced capability for cellular internalization by cellular uptake studies using confocal laser scanning microscopy (CLSM). In vivo studies demonstrated that the oral insulin delivery system produced a pronounced and long-lasting hypoglycemia effect in diabetic mice. In conclusion, the muco-inert nanocomplex based on L-valine-modified chitosan and fucoidan presents a promising platform for effective oral insulin delivery.

It is a matter of debate whether chondrocytse hypertrophy is an active driver of age-related Osteoarthritis (OA) or a passive consequence of OA. Understanding the progression of hypertrophy can be crucial in developing effective disease-modifying therapeutics. To clarify this, we investigated biochemical signatures associated with human healthy cartilage and hypertrophic reactivation in human OA cartilage using a multimodal spectroscopic approach. Healthy adult cartilage and OA samples spanning different disease stages were analyzed using ATR-FTIR, XPS, Raman spectroscopy, DMMB and hydroxyproline assays, along with histology. Across all modalities, OA cartilage exhibited distinct molecular features consistent with a hypertrophic-like shift: pronounced GAG depletion, collagen network disruption, loss of collagen-specific spectral peaks, and elevated oxidative modifications in the ECM. Quantitative assays confirmed reduced GAG and total collagen content, aligning with biochemical patterns observed during endochondral maturation. Raman profiles further captured molecular rearrangements linked to matrix mineralization pathways typically associated with hypertrophic differentiation. Histological evaluation validated the progressive ECM disorganization and GAG loss, reinforcing the spectroscopic findings. Overall, these integrated results suggest that in OA, chondrocyte hypertrophy is not merely a passive consequence, but OA reflects a modified reactivation of endochondral ossification.

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.