Macromolecular bioscience最新文献

Third-degree burns result in extensive damage to the skin's epidermal and dermal layers, with limited treatment options available. Currently, xenogeneic collagen-based skin grafts are used as scaffolds to integrate into the wound bed and provide a template for neodermis formation. Existing commercial products like Integra dermal templates rely on a time-consuming and variable dehydrothermal (DHT) crosslinking process. This study presents a novel crosslinking process for collagen sponges, utilizing UV irradiation followed by glutaraldehyde (GA) crosslinking. This UV method allows to fine-tune the template's crosslink density and degradation profile while significantly reducing the total crosslinking time from 48 to 24 h compared to DHT/GA crosslinking. In vitro characterization and in vivo validation are conducted using a full-thickness skin wound mouse model. The collagen template supports the human dermal fibroblast cell line WS-1 proliferation more effectively than the Integra template after 2 weeks in culture. Additionally, in vivo data indicate a similar level of regeneration of full-thickness skin wounds in mouse models between the sponge and Integra templates. Furthermore, the sponge template does not elicit any abnormal angiogenic or immune responses. The crosslinking approach offers a promising alternative production process for collagen sponge scaffolds.

Irinotecan hydrochloride (CPT-11) is one of the first-line drugs used in the clinical treatment of colorectal cancer (CRC). However, the concomitant adverse effect of delayed diarrhea has hindered its clinical use. CPT-11 combined with Thalidomide (THA) therapy is considered a palliative strategy. To optimize the synergistic treatment of CPT-11 and THA, co-loaded liposomes are constructed using cholesterol, lecithin, and 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE-PEG) as the “immune and gut microbiota regulator.” The co-loaded liposomes, which possess good stability, are prepared by the solvent injection method. After the treatment with the co-loaded liposomes, tumor growth in CRC-bearing mice is significantly inhibited. In particular, the co-loaded liposomes demonstrate favorable diarrhea-relieving effects through the modulation of inflammatory cytokines and gut microbiota. These findings suggest that the co-loaded liposomes have great potential as a combined drug-delivery platform for CRC therapy.

Biologics targeting matrix-degrading proteases, cartilage repair, and inflammation are emerging as promising approaches for osteoarthritis (OA) treatment. Recent research highlights biologic-human placental tissue (HPT) as a potential OA therapy due to its biocompatibility, abundant protein biofactors, and ability to reduce cartilage degradation by suppressing protease expression. Microneedles (MNs) are receiving growing attention for enhancing transdermal delivery of biologics as an alternative to conventional subcutaneous injections. The lyophilized human placental extract (LHP) loaded polymeric MNs are fabricated using a micromolding technique for transdermal delivery. Ex vivo release studies reveal that MNs exhibit a gradual and consistent release of LHP, indicating a sustained delivery profile. LHP-MNs are nontoxic and anti-inflammatory in nature against human skin cells and interleukin (IL-1β) induced synovial cells. Furthermore, the in vivo study shows that LHP-MNs substantially improve behavioral parameters in OA rat models and lower serum concentrations of tumor necrosis factor- α (TNF-α) and cartilage oligomeric matrix protein (COMP) biomarkers, thereby alleviating knee and ankle joint injuries. Histopathological analysis indicates that LHP-MNs significantly preserve cartilage integrity. The study results suggest that employing polymeric MNs for transdermal delivery of LHP can be a promising treatment approach for OA, with the added benefit of excellent patient compliance.

Front Cover: In article 2400419, Chandan Maity and co-workers demonstrate control over the formation of a supramolecular hydrogel material at ambient conditions. Addition of H₂O₂ results in situ generation of hydrogelator that self-assembles to the hydrogel network. Local availability of H₂O₂ allows obtaining free-standing hydrogel material.

The synthesis of fluorescent hybrid nanomaterials engineered via the chain-end modification of reversible addition-fragmentation chain-transfer (RAFT) polymers on the surface of bovine serum albumin (BSA) protein-stabilized gold nanoclusters (AuNCs@BSA) is described. Based on the “grafting-to” approach the core-shell structured nanoconjugates AuNCs@BSA/polymer are generated via effective ligation of hydrophilic, and stimuli-responsive polymers. Such nanomaterials are characterized via various microscopic and spectroscopic studies and exhibit their size as ≈5 nm and emission peak at ≈650 nm. Interestingly, the conjugation of thermoresponsive polymer poly(diethylene glycol monomethyl ether methacrylate) (PDEGMA) transformed the nanoconjugates AuNCs@BSA/PDEGMA as dual thermo/pH-responsive nanomaterials.

In advancing cardiac tissue engineering (CTE), the development of injectable hydrogels mirroring myocardial properties is pivotal. The designed hydrogels must not only support cardiac cell growth but also have to be conductive to properly promote the functionalities of cardiac cells. Here, a facile approach is developed to incorporate gold nanoparticles (AuNPs) into an injectable hydrogel composed of Alginate (Alg) and Gelatin (Gel). The resultant nanocomposite hydrogel boasts a porous interconnected network and superior conductivity (2.04 × 10–4 S cm⁻¹) compared to the base Alg/Gel hydrogel. Hydrogel hydration and in vitro degradation profiles affirm their suitability as carriers for cardiac cells. Importantly, Alg/Gel+AuNPs hydrogels exhibit no toxicity to mouse Embryonic Cardiac Cells (mECCs) over 7 days, elevating connexin 43 (Cx43) and cardiac troponin T (CTnT) gene expression compared to controls. Then, the Alg/Gel+AuNPs hydrogel is used as a carrier for intramyocardial delivery of mECCs in rats with myocardial infarction. The significant increase in α-Smooth Muscle Actin (α-SMA) and cardiac troponin T (CTnT) expression along with the increase in ejection fraction (EF), smaller infarction size, less fibrosis area confirmed that the hydrogel efficiently promoted the transmission of mechanical and electrical signals between transplanted cells and surrounding tissue.

Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100–300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.

Electrospun nanofibrous membranes made of chiral selectors (CSs) have shown their potential for efficient chiral resolutions via filtrations. It is thus of great importance to expand the number of electrospun membranes made of various CSs for the resolution of a wide range of chiral compounds. Here, the electrospinning of two benzyl carbamate derivatives of cellulose, namely cellulose benzyl carbamate (CBzC) and cellulose 4-chlorobenzyl carbamate (CCBzC), to form a new type of enantioselective membranes for chiral resolutions of racemic compounds, is reported. The morphology of the electrospun membranes is studied by optical microscopy and scanning electron microscopy in relation to the electrospinning process parameters. Liquid-liquid permeation experiments of the racemic compounds, (R,S)-1-(1-naphthyl)ethanol ((R,S)-NET), (R,S)-1,1′-bi-2-naphtol ((R,S)-BNP), (R,S)-naproxen ((R,S)-NAP), and (R,S)-benzoin ((R,S)-BNZ) through the membranes demonstrate preferable permeations of (R)- or (S)-enantiomers depending on the combinations between the CSs and the racemates. Molecular docking simulations indicate the differences in the binding type, number, and free energies between the CSs and the enantiomers.

A strategy for multifunctional biosurfaces exploiting multiblock copolymers and the antipolyelectrolyte effect is reported. Combining a polyzwitterionic/antifouling and a polycationic/antibacterial block with a central anchoring block for attachment to titanium oxide surfaces affords surface coatings that exhibit antifouling properties against proteins and allow for surface regeneration by clearing adhering proteins by employing a salt washing step. The surfaces also kill bacteria by contact killing, which is aided by a nonfouling block. The synthesis of block copolymers of 4-vinyl pyridine (VP), dimethyl 4-vinylbenzyl phosphonate (DMVBP), and 4-vinylbenzyltrimethyl ammonium chloride (TMA) is achieved on the multigram scale via RAFT polymerization with good end group retention and narrow dispersities. By polymer analogous reactions, poly(4-vinyl pyridinium propane sulfonate-block-4-vinylbenzyl phosphonic acid-block-4-vinylbenzyl trimethylammonium chloride) (P(VSP₆₄-b-PA₁₄-b-TMA₆₄)) is obtained. The antifouling properties against the model protein pepsin and the salt-induced surface regeneration are shown in surface plasmon resonance (SPR) experiments, while independently the antibacterial and antifouling properties of coated titanium substrates are successfully tested in preliminary microbiological assays against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This strategy may contribute to the development of long-term effective antibacterial implant surface coatings to suppress biomedical device-associated infections.