Biomaterials Science最新文献

Granular hydrogels are an emerging biomaterial platform increasingly used in biomedical applications, including therapeutic delivery and tissue regeneration. Assembled from micron-scale hydrogel particles through physical assembly or chemical cross-linking, granular hydrogels possess micro- and macroscopic pores that facilitate molecular transport and cell migration. However, current granular hydrogels are typically fabricated with defined stiffness, porosity, and compositions that do not recapitulate the dynamic nature of native tissues, including the tumor microenvironment. To address this challenge, we have developed dynamic granular hydrogels formed by gelatin-norbornene-carbohydrazide (GelNB-CH) microgels. GelNB-CH microgels were first prepared from a microfluidic droplet generator coupled with the rapid thiol-norbornene photo-click gelation. The collected microgels were annealed via inverse electron-demand Diels-Alder (iEDDA) click reaction to form granular hydrogels, which were dynamically stiffened via hydrazone bonding. Notably, adjusting the concentration of the stiffening reagent (i.e., oxidized dextran, oDex) enabled dynamic stiffening of the granular hydrogels without affecting the void fraction. Pancreatic cancer-associated fibroblasts (CAFs) seeded in the granular hydrogels spread rapidly throughout the scaffold and induced cancer cell migration. This work enhances the design of granular hydrogels, offering a highly adaptable biomaterial platform for in vitro cancer modeling.

Expression of Concern for 'A multifunctional substance P-conjugated chitosan hydrochloride hydrogel accelerates full-thickness wound healing by enhancing synchronized vascularization, extracellular matrix deposition, and nerve regeneration', Hao Li et al., Biomater. Sci., 2021, 9, 4199-4210, https://doi.org/10.1039/D1BM00357G.

Head and neck squamous cell carcinoma (HNSCC) presents significant therapeutic challenges owing to its elevated recurrence rate and resistance to chemotherapeutic interventions. Tumor organoid models serve as essential platforms for investigating tumor physiology and pathological functions in vivo for its similarities in recapitulating the spatial structure of HNSCC. We employed HPSCC organoids from typical cell line and patient tissues, which faithfully recapitulated the tumor architecture, combined with CRISPR/Cas9 screening and TCGA-HNSCC database analysis. We identified SREBP1, a master regulator of lipid metabolism, as a key molecule whose expression escalates during HNSCC progression and correlates with improved patient survival and chemotherapy response. Functional studies demonstrated that SREBP1 downregulation conferred resistance to cisplatin and reduced cell death in both organoid and xenograft models in human hypopharyngeal carcinoma (HPSCC). We also found that the downregulation of SREBP1 was associated with enhanced resistance to cisplatin and a reduction in cell death in HPSCC-organoid models ex vivo and xenograft mouse models in vivo. Our findings establish SREBP1-mediated lipid rewiring as a critical determinant of HNSCC pathogenesis and treatment outcomes. Consequently, our model offers a promising solution for the swift and accurate evaluation of chemotherapy efficacy and identifies SREBP1 as a potential therapeutic target in HPSCC.

Expression of Concern for: '3D-printed dimethyloxallyl glycine delivery scaffolds to improve angiogenesis and osteogenesis', Zhu Min et al., Biomater. Sci., 2015, 3, 1236-1244, https://doi.org/10.1039/C5BM00132C.

Correction for 'Facilely printed silk fibroin hydrogel microparticles as injectable long-lasting fillers' by Chunyu Xie et al., Biomater. Sci., 2024, 12, 375-386, https://doi.org/10.1039/D3BM01488F.

The meniscus is one of the most injured structures in the human knee. Current clinical approaches do not adequately replace or regenerate the meniscus. Complete or partial meniscus removal leads to degenerative articular changes due to abnormal mechanical forces. Tissue engineering (TE) of the meniscus or developing non-tissue-engineered implants may offer efficient solutions. Yet, these approaches are challenging due to the requirement of a complex, non-toxic three-dimensional (3D) structure exhibiting adequate biomechanical and biological properties. In this study, we developed a porous 3D printed acrylate end-capped urethane-based poly(ethylene glycol) (AUP) hydrogel scaffold via extrusion-based 3D printing for meniscus implant application. With the aim to meet the required biomechanical properties, we studied the effects of two different scaffold variables. Indeed, in addition to the poly(ethylene glycol) (PEG) backbone molar mass (4000 versus 8000 g mol^-1), we also varied the scaffold design. The latter included variations in the scaffold pore size (200 µm, 350 µm and 500 µm) and the strut diameter (230 µm versus 370 µm). The morphology of the developed AUP hydrogel scaffolds was characterized via optical microscopy and nano-computed tomography (nano-CT), showing regular, porous, interconnected 3D hydrogel scaffolds. The physical properties of the scaffolds, including the gel fraction (75-89%), the swelling degree (230-500%) and the compressive modulus (0.5-3.2 MPa), depended on the scaffold design and the backbone molar mass. Surface analyses through X-ray photoelectron spectroscopy (XPS) showed the successful application of a photo-crosslinkable gelatin derivative (known as gel-MOD or gel-MA) on the printed AUP hydrogel scaffolds (as reflected by an N/C value of 0.06 for gel-MOD modified AUP versus no signal for non-modified AUP scaffolds). Live/dead staining and the MTT assay using human dermal fibroblasts (HDF) revealed the non-toxic behavior of the developed AUP scaffolds (90% cell viability). This study clearly demonstrates the potential of the developed AUP hydrogel scaffolds as meniscal implants, as the applied polymer and 3D printing technologies enable the development of non-toxic 3D porous scaffolds, of which both the cell-interactive character and the mechanical properties can be controlled.

Nowadays, with the growing need for alternative antibacterial materials for the treatment of bacterial infections, TiO₂ with antibacterial properties has attracted attention as a potential antibacterial agent. Ni-TiO₂ and Co-TiO₂ nanofibers (NFs) were synthesized via an electrospinning process. The antibacterial activities of these NFs against S. aureus and E. coli were evaluated under UV-light illumination using optical density measurements. Co-TiO₂ exhibited superior antibacterial activity against both S. aureus and E. coli under UV-light irradiation. The antibacterial mechanism was further investigated through a glutathione (GSH) oxidation assay and morphological analysis using scanning electron microscopy (SEM). Hydrophilicity was evaluated by contact angle measurement. The antibiofilm activities of TiO₂, Ni-TiO₂, and Co-TiO₂ NFs were investigated with respect to E. coli and S. aureus biofilms. Ni-TiO₂ and Co-TiO₂ demonstrated more effective antibiofilm activities than bare TiO₂. Under UV-light irradiation, the biofilm inhibition efficacy was increased for both Ni-TiO₂ and Co-TiO₂ NFs while Co-TiO₂ NFs were found to have the greater antibiofilm performance. Additionally, in silico analysis was conducted to explore the molecular interactions of the NFs with S. aureus Immunoglobulin-Binding B Domain (PDB ID: 1BDD) and FimH lectin protein of E. coli (PDB ID: 4XO8). Co-TiO₂ exhibited stronger binding to S. aureus, while TiO₂ showed stronger binding to E. coli.

Hyaluronic acid (HA) binds the transmembrane glycoprotein cluster of differentiation-44 (CD44), a highly expressed surface receptor that plays a critical role in tumor growth, invasion, and metastasis. Approaches to target CD44 utilize biologically sourced HA which inherently suffers from molecular weight (MW) heterogeneity and biological contaminants. Fully synthetic approaches to HA are attractive and circumvent these biological contaminants; however, readily accessing oligomers of six monosaccharides or more, as is required for CD44 binding, is challenging. To this end, we report the synthesis of glycopolymers functionalized with HA disaccharide pendant chains. These well-defined and regioselective polymers consist of glucose monomers linked via α-1,2 amide bonds, termed polyamidosaccharides, functionalized with branched HA disaccharide moieties interspersed throughout via a strain-promoted azide-alkyne cycloaddition. Among these homopolymers and copolymers, two of the polymers bearing the highest HA disaccharide conjugation bind CD44 with nanomolar affinity. Assays using a rhodamine-labelled polymer reveal a positive relationship between cellular internalization and CD44 expression levels in breast cancer cells. Conjugation of paclitaxel to the polymer enhances paclitaxel potency in CD44-expressing cancer cells compared to free paclitaxel.

The development of efficient and multifunctional nanosystems is crucial for enhancing anticancer therapy. The incorporation of therapeutic agents in nanocarriers often results in premature drug release, leading to unsatisfactory therapeutic effects. To overcome these challenges, a nanosystem, MOF@Cu/Ru/Pt (MOF = metal-organic framework UiO-67(bpy), bpy = bipyridine, Cu = copper peroxide, Ru = [Ru(bpy)₃]²⁺, and Pt = Pt(IV) prodrug), is synthesized. The chemotherapeutic Pt(IV) prodrug can coordinate with the MOF and act as a gating agent for the confinement and the glutathione-responsive controlled release of Cu and Ru species, respectively, for chemodynamic/photothermal and photodynamic therapies. Upon exposure to near-infrared irradiation, this material facilitates the enhanced generation of reactive oxygen species and a temperature rise. The in vitro studies of MOF@Cu/Ru/Pt demonstrate excellent biocompatibility in normal cells and remarkable therapeutic efficacy in 4T1 cancer cells, attributed to the synergistic anticancer effects.

Synthetic biodegradable microspheres hold great promise for complex wound repair. However, their clinical application is hindered by inflammatory responses triggered by acidic degradation byproducts. In this paper, we developed new composite microspheres as dressings to accelerate infected wound healing. Polyethylene glycol/poly(L-lactide)/poly(ε-caprolactone) multiblock copolymers were synthesized and engineered with Cu-doped bioactive glass to form composite microspheres. The Cu-doped bioactive glass not only improved the hydrophilicity of the composite microspheres but also neutralized the acidic degradation products of the copolymers. This helped preserve a physiologically neutral pH in wounds, thereby attenuating inflammatory stimulation and fostering a stabilized microenvironment supportive of efficient wound healing. Simultaneously, the Cu²⁺ ions within the bioactive glass network were released gradually over 24 h to maintain sustained antibacterial activity and promote wound regeneration. Animal experiments demonstrated that the composite microspheres significantly accelerated the healing of wounds infected with Staphylococcus aureus. These composite microspheres represent a feasible solution for infected wound healing.