Macromolecular bioscience最新文献

Osteoporotic bone regeneration is challenging due to impaired bone formation. Tetrahedral DNA nanostructures (TDN), promising nucleic acid nanomaterials, have garnered attention for their potential in osteoporotic mandibular regeneration owing to their ability to enhance cellular activity and promote osteogenic differentiation. Osteoblasts play a critical role in bone regeneration; however, intracellular delivery of TDN into osteoblasts remains difficult. In this study, a novel osteoblast-targeted CH6 aptamer-functionalized TDN (TDN-CH6) is aimed to develop for osteoporotic mandibular regeneration. This results demonstrated that TDN-CH6 exhibits superior osteoblast specificity and efficient recruitment to bone fracture sites. Furthermore, TDN-CH6 significantly enhances cellular activity and osteogenic differentiation compared to TDN alone. Notably, Gelatin Methacryloyl (GelMA) hydrogels incorporating TDN and TDN-CH6 shows improved biological performance and are favorable for osteoporotic mandibular regeneration, suggesting that this platform represents a promising strategy for addressing complex bone defects.

The challenge of nerve regeneration stems from the diminished vitality of mature neurons post-injury. The construction of a suitable microenvironment at the injury site to facilitate axonal regeneration is a crucial aspect of nerve injury repair. In this work, a conductive and biocompatible composite material, CP/HA/HGF, is designed by grafting polypyrrole onto chitosan and compounding it with hyaluronic acid and functional short peptides for neural regeneration. Comprehensive material characterizations shows that CP/HA/HGF holds the potential as a scaffold material based on its good overall performance. In vitro experiments revealed that the combination of conductive composite scaffolds and electrical stimulation facilitated axonal growth and myelin formation in the dorsal root ganglion, while also promoting the migration of Schwann cells. Therefore, the conductive composite scaffold studied in this paper presents a promising strategy for enhancing neural regeneration.

Multicomponent self-assembly represents a cutting-edge strategy in peptide nanotechnology, enabling the creation of nanomaterials with enhanced physical and biological characteristics. This approach draws inspiration from the highly complex nature of the native extracellular matrix (ECM) constituting multicomponent biomolecular entities. In recent years, the combination of bioactive peptide with polymer has gained significant attention for the fabrication of novel biomaterials due to their inherent specificity, tunable physiochemical properties, biocompatibility, and biodegradability. This advanced strategy can address the limitation of the lower mechanical strength of the individual peptide hydrogel by incorporating the biopolymer, resulting in the formation of a composite scaffold. In this direction, this advanced strategy is explored using noncovalent interactions between cellulose nano-fiber (CNF) and cationic Cardin-motif peptide to develop advanced composite scaffolds. The bioactive cationic peptide otherwise failed to form hydrogel at physiological conditions. Interestingly, the differential mixing ratio of CNF and peptide modulated the surface charge, functionality, and mechanical properties of the composite scaffolds, resulting in diverse cellular responses. 10:1 (w/w) ratio of CNF and peptide-based composite scaffold demonstrates improved cellular survival and proliferation in 2D culture conditions. Notably, in 3D cultures, cell proliferation on the 10:1 matrix is comparable to Matrigel, highlighting its potential for advanced tissue engineering applications.

Blood-contacting medical devices, especially extracorporeal membrane oxygenators (ECMOs), are highly susceptible to surface-induced coagulation because of their extensive surface area. This can compromise device functionality and lead to life-threatening complications. High doses of anticoagulants, combined with anti-thrombogenic surface coatings, are typically employed to mitigate this risk, but such treatment can lead to hemorrhagic complications. Therefore, bioactive surface coatings that mimic endothelial blood regulation are needed. However, evaluating these coatings under realistic ECMO conditions is both expensive and challenging. This study utilizes microchannel devices to simulate ECMO fluid dynamics and assess the clot-lysis efficacy of a self-activating fibrinolytic coating system. The system uses antifouling polymer brushes combined with tissue plasminogen activator (tPA) to induce fibrinolysis at the surface. Here, tPA catalyzes the conversion of blood plasminogen into plasmin, which dissolves clots. This positive feedback loop enhances clot digestion under ECMO-like conditions. This findings demonstrate that this coating system can significantly improve the hemocompatibility of medical device surfaces.

Implant-integrated drug delivery systems that enable the release of biologically active factors can be part of an in situ tissue engineering approach to restore biological function. Implants can be functionalized with drug-loaded nanoparticles through a layer-by-layer assembly. Such coatings can release biologically active levels of growth factors. Sustained release is desired for many in vivo applications. The layer-by-layer technique also allows for the addition of extra layers, which can serve as "barriers" to delay the release. Electrospun Polycaprolactone (PCL) fiber mats are modified with a Chitosan (CS) grafted with PCL sidechains (CS-g-PCL₂₄) and coated with transforming growth factor beta 3 (TGF-β₃) loaded Chitosan/tripolyphosphate nanoparticles as a drug delivery system. Additional layers including polystyrene sulfonate, alginate, carboxymethyl cellulose, and liposomes (phosphatidylcholine) are applied. Streaming potential and X-ray photoelectron spectroscopy (XPS) measurements indicated a strong interpenetration of the chitosan and polyanion layers, while liposomes formed separate layers, which are more promising for sustained release. All samples release TGF-β₃ at different cumulative levels without altering release kinetics. Variations in layer structure, interpenetration, and stability depending on the chitosan used are observed, which ultimately has minimal impact on the release kinetics. Polyelectrolyte layers strongly interpenetrated the active layers and therefore do not act as effective diffusion barriers, while the liposome layer, though separated, lacked sufficient stability.

Hygrophila ringens var. ringens is a medicinal plant of the Acanthaceae family. A soluble polysaccharide is extracted from H. ringens seeds using warm water, followed by deproteinization and purification using column chromatography. DL1 is characterized comprehensively using spectroscopic and chromatographic techniques and identified as a polymer containing xylose (Xyl; 78.5%) and 4-O-methyl-d-glucuronic acid (4-O-MeGlcA; 21.5 %). The most prominent glycosidic linkages detected are terminal-xylose (T-Xyl); 1,2,3,4-Xylp; 1,2,4-Xylp; and T-4-O-MeGlcA. DL1 belongs to the xylan group and is a 4-O-methylglucuronoxylan. DL1 exhibits inhibition of bovine serum albumin denaturation with IC₅₀ values of 0.35 mg mL^-1 and a similar activity to diclofenac (non-steroidal anti-inflammatory drug). In a model of lipopolysaccharide-stimulated macrophages, DL1 (20-40 µg mL^-1) strongly inhibits inflammatory cytokines and reactive oxygen species release without having significant macrophage cytotoxicity. The inhibitory effect of DL1 on inflammatory cytokines is mediated by the activation of mitogen-activated protein kinases by inhibiting the phosphorylation of p38 and extracellular signal-regulated kinase. These results highlight the potential of DL1 for treating inflammation through its cytokine-suppressive activity.

To address the rising prevalence of bacterial infections and the need for innovative therapeutic solutions, this study has developed a novel antibacterial hydrogel composite composed of Aloe vera, gelatin, sodium alginate, and Sterculia monosperma-silver nanoparticles (SM-AgNPs) loaded curcumin-nanoliposomes (NLPs). The aloe vera/gelatin/sodium alginate hydrogels (AGS) are prepared using different weight ratios of Aloe vera, gelatin, and sodium alginate, aiming to optimize mechanical properties and biocompatibility for biomedical applications. The incorporation of SM-AgNPs and curcumin-loaded NLPs enhanced the hydrogels' antibacterial properties. Characterizations of the hydrogels are performed by using Fourier-transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Additional examinations, such as water absorption analysis, rheology measurements, thermal stability, and injectability, along with pH and temperature responsiveness, are also conducted. The AGS-3 hydrogel formulation, with a 1:5:3 ratio of Aloe vera to gelatin to sodium alginate, exhibited significant performance in all tests, making it suitable for further experiments. Furthermore, antimicrobial activity assays showed that AGS hydrogels containing SM-AgNPs/NLP composites effectively inhibited the growth of both gram-positive Staphylococcus aureus (S.aureus) and gram-negative Escherichia coli (E.coli) bacteria. These results indicate that the SM-AgNPs/NLP-AGS hydrogel is a promising material for biomedical applications including wound healing, infection prevention, and targeted drug delivery.

Photocrosslinkable formulations based on the radical thiol-ene reaction are considered better alternatives than methacrylated counterparts for light-based fabrication processes. This study quantifies differences between thiol-ene and methacrylated crosslinked hydrogels in terms of precursors stability, the control of the crosslinking process, and the resolution of printed features particularized for hyaluronic acid (HA) inks at concentrations relevant for bioprinting. First, the synthesis of HA functionalized with norbornene, allyl ether, or methacrylate groups with the same molecular weight and comparable degrees of functionalization is presented. The thiol-ene hydrogel precursors show storage stability over 15 months, 3.8 times higher than the methacrylated derivative. Photorheology experiments demonstrate up to 4.7-times faster photocrosslinking. Network formation in photoinitiated thiol-ene HA crosslinking allows higher temporal control than in methacrylated HA, which shows long post-illumination hardening. Using digital light processing, 4% w/v HA hydrogels crosslinked with a dithiol allowed printing of 13.5 × 4 × 1 mm³ layers with holes of 100 µm resolution within 2 s. This is the smallest feature size demonstrated in DLP printing with HA-based thiol-ene hydrogels. The results are important to estimate the extent to which the synthetic effort of introducing -ene functions can pay off in the printing step.