Expression of concern for 'Shell-crosslinked knedel-like nanoparticles induce lower immunotoxicity than their non-crosslinked analogs' by Mahmoud Elsabahy et al., J. Mater. Chem. B, 2013, 1, 5241-5255, https://doi.org/10.1039/C3TB20668H.
Without functionalization, reconstituted collagen gels demonstrate poor mineralization in vitro and in vivo. Due to their high reactivity, bioactive sol-gel-derived borate-glasses (SGBGs) rapidly convert to carbonated hydroxyapatite (CHA) in vitro....
The formation of Pseudomonas aeruginosa (P. aeruginosa) biofilm significantly enhances bacterial resistance to antimicrobial agents and escape from the host immune system, making the treatment of related infections considerably more challenging. As a potential approach for anti-biofilm strategies, the inhibition of lectins often relies on multivalent interactions to enhance binding affinity between the inhibitor and its target. In this study, targeting the P. aeruginosa lectin LecA, we constructed a polyethylene glycol-based multivalent galactoside, termed 4-Arm-PEG-Gal, by modifying the termini of 4-Arm-PEG with galactosides specific to LecA. The results indicate that 4-Arm-PEG-Gal significantly disrupts mature biofilm and is specifically recognized by the lectin LecA. Compared to the use of antibiotics alone, the combination of 4-Arm-PEG-Gal and TOB reduces antibiotic usage by 75% and additionally eradicates 73% of the bacteria within the biofilm. Furthermore, in a model of chronic lung infection, the combination of 4-Arm-PEG-Gal and TOB cleared all bacteria from the lungs, significantly reduced the secretion of TNF-α and IL-6 in the lungs, and effectively ameliorated lung damage caused by bacterial infection.
Ischemic stroke (IS) and the subsequent reperfusion induce severe oxidative stress and mitochondrial dysfunction through the excessive generation of reactive oxygen species (ROS). However, most existing therapeutic strategies target only a single pathological pathway, thereby limiting their therapeutic efficacy. Herein, we developed a multifunctional mesoporous copper-enriched Prussian blue nanozyme (Meso-Cu-PBMc) by synergistically integrating Cu2+ active sites within a Prussian blue framework, exhibiting robust multi-enzymatic mimetic activities, including superoxide dismutase (SOD)-, catalase (CAT)-, and peroxidase (POD)-, facilitating efficient ROS scavenging and the restoration of intracellular redox homeostasis. In vitro studies demonstrated that Meso-Cu-PBMc effectively protects neuronal cells against CoCl2-induced oxidative injury and significantly reduces intracellular ROS accumulation. In a middle cerebral artery occlusion/reperfusion (MCAo/R) rat model, intranasal administration of Meso-Cu-PBMc (20 mg kg-1) at the onset of reperfusion markedly reduced infarct volume from 54.32% to 13.03%, significantly improved neurological function, and enhanced locomotor recovery in a dose-dependent manner. Mechanistically, the nanozyme exerted dual therapeutic effects through both direct ROS scavenging and activation of the Nrf2/xCT/GPX4 antioxidant signaling pathway, thereby maintaining glutathione homeostasis and cellular redox balance. Furthermore, treatment restored the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95), increased the levels of SIRT1 and PGC-1α, and reduced the expression of GFAP and iNOS, indicating the preservation of neuronal plasticity and mitochondrial homeostasis, together with the attenuation of reactive gliosis. Collectively, these findings highlight Meso-Cu-PBMc as a promising therapeutic platform for the treatment of ischemia-reperfusion injury and other oxidative stress-associated neurological disorders.
Sinusitis often requires functional endoscopic sinus surgery (FESS), but postoperative bleeding and persistent inflammation remain critical challenges. This study developed a multifunctional composite sponge (GSPB) using γ-polyglutamic acid (γ-PGA) and sodium alginate (SA) as the matrix, with Generation 3 polyamidoamine (PAMAM) dendrimer (G3) serving as both cross-linkers and budesonide (Bud) solubilizers. Fabricated via EDC/NHS-mediated cross-linking and freeze-drying, GSPB exhibited a porous structure, a balanced compressive modulus of 41.95 ± 3.50 kPa, and excellent cyclic compression fatigue resistance (stress attenuation rate of only 8.98% after 50 compression cycles). It also showed rapid absorption toward water and blood, alongside full biodegradability within 21 days. Meanwhile, G3 elevates the aqueous solubility of Bud by 12.5 times, thereby achieving long-term sustained drug delivery. In vitro studies confirmed excellent biocompatibility, potent hemostatic efficacy, and anti-inflammatory activity. In vivo experiments using nasal bleeding and acute sinusitis models demonstrated that GSPB achieved faster hemostasis with less blood loss than commercial gelatin sponges and Nasopore. It also effectively suppressed mucosal inflammation, reduced collagen deposition, and inhibited goblet cell hyperplasia without systemic toxicity, verified by serum biochemistry, routine blood tests, and major organ H&E histological staining in mice. As a biodegradable scaffold integrating hemostasis and anti-inflammatory activity, GSPB provides a novel and promising solution for post-sinusitis surgery care, with significant clinical translational potential.
The healing of diabetic wounds is impeded by a pathological triad of recalcitrant bacterial infections, oxidative stress, and chronic inflammation. While photothermal therapy (PTT) is a promising non-antibiotic alternative, its...
The therapeutic efficacy of cisplatin-based chemotherapy for lung cancer is often limited by low tumor specificity and off-target toxicity. To address these challenges, we have developed a biomimetic “Trojan horse”...
Medical nylon catheters (PA12) are essential instruments in interventional procedures, yet their inherent surface hydrophobicity and limited lubricity significantly restrict clinical performance. Although various hydrophilic coatings have been developed to address these issues, traditional physical coating methods often suffer from poor adhesion and delamination during use. To overcome these drawbacks, we developed a two-step chemical modification strategy involving epichlorohydrin (ECH) activation followed by covalent grafting of polyethyleneimine (PEI), aiming to construct a stable hydrophilic lubricating layer on PA12 catheter surfaces. XPS analysis revealed a marked change in the surface chemical composition, indicating the successful covalent grafting of PEI. The modified catheter exhibited a surface amino group density of 2.7229 µmol mm-2, approximately four times higher than that of the pristine PA12 catheter, indicating the successful grafting of PEI molecules onto the catheter surface. This modification markedly enhanced surface hydrophilicity, reducing the water contact angle from 103.54° to 62.01°, decreasing the friction coefficient by 36.9%, and nearly doubling water absorption. Moreover, the modified catheter displayed promising in vitro biocompatibility, as evidenced by non-cytotoxic extracts, a hemolysis rate of only 0.65%, and no detectable adverse effects on blood cell counts. Overall, this study presents a covalent grafting-based surface functionalization strategy for PA12 interventional catheters that improves both lubricity and surface hydrophilicity while retaining in vitro biosafety. These findings provide a basis for future investigations into the long-term stability and in vivo performance of the modified catheters.
Carboxylesterase 2 (CES2) is a clinically significant serine hydrolase that governs the metabolic activation and detoxification of numerous ester-containing drugs and prodrugs. Despite its pivotal role in liver and colorectal cancer progression, direct in situ imaging of CES2 activity remains challenging due to the scarcity of probes with high isoform selectivity. To address this, we herein present XM-CE, a rationally engineered near-infrared (NIR) fluorescent probe specifically optimized for the highly sensitive and selective monitoring of CES2 activity. By integrating a CES2-responsive ester trigger with the XM-OH fluorophore, XM-CE yields a pronounced fluorescence turn-on response at 635 nm upon enzymatic hydrolysis. The probe demonstrates exceptional sensitivity with a limit of detection (LOD) of 0.023 U mL-1, alongside superior biocompatibility. These attributes enable high-resolution, real-time visualization of endogenous CES2 dynamics in living cells, zebrafish larvae, and tumor-bearing murine models. Collectively, our findings establish XM-CE as a robust analytical tool for mapping tissue-specific expression and monitoring enzyme regulation in vivo, offering significant potential for advancing biomedical research and clinical diagnostics.
Cell-biomaterial interactions involve the adsorption of proteins on material surfaces, followed by biophysical interactions among adsorbed proteins and cell surface integrins. In a series of recent publications, it has been demonstrated that the cell fate processes can be guided by the electric field stimulations on a range of biomaterial substrates, in vitro. In efforts to understand the underlying biophysical process, molecular dynamics (MD) simulation studies indicated the role of electrical stimuli in fibronectin protein adsorption on biomaterial substrates. While molecular dynamics (MD) studies on protein adsorption on biomaterial surfaces have gained significant traction, such studies on integrin-protein interactions within the extracellular space remain relatively unexplored. Against this perspective, this work provides the mechanistic insights into the role of electric fields in fibronectin-integrin interactions and integrin clustering in the extracellular space. The present study involves the analysis of global descriptors, including interaction energy, root mean square deviation, radius of gyration, and center-of-mass distance, together with residue-level metrics such as residue-residue contact maps, hydrogen-bond and salt-bridge persistence, RGD-loop orientation, interfacial solvent-accessible surface area, and secondary-structure evolution among the interacting proteins, in a system comprising of 636 210 atoms. In summary, the outcomes of the present work enable a better understanding of the molecular mechanisms underlying exogenous electric-field-mediated cell-biomaterial interactions.
Natural products remain an important source of bioactive molecules, but their translation is often limited by inefficient identification of target-relevant constituents and poor in vivo delivery. Cell membrane-based technologies offer a promising way to address these two challenges through membrane-affinity screening and biomimetic membrane nanocarriers. However, these approaches have usually been developed as separate strategies rather than as connected stages of natural-product translation. In this review, we propose a membrane-centered discovery-to-delivery framework in which cell membranes function as programmable biointerfaces linking upstream compound discovery with downstream nanomedicine design. Cell membrane chromatography and related affinity platforms can preserve disease-relevant receptor contexts and enrich membrane-interacting constituents from complex natural-product mixtures. In parallel, cell membrane-biomimetic nanocarriers can inherit functional membrane components, including proteins, glycans and self-recognition signals, thereby improving circulation, lesion targeting, immune modulation and therapeutic efficacy. We further introduce a "two-membrane, one-target" strategy, in which the screening membrane and delivery membrane do not need to be identical but should be connected by a validated receptor- or interface-level recognition mechanism. By integrating evidence-ranked screening studies with biomimetic delivery systems, this review highlights the importance of distinguishing binding identification, functional validation, in vivo efficacy and translational feasibility. This membrane-centered perspective provides a structured framework for improving the mechanistic rigor and translational potential of natural-product-based nanomedicine.
Nisha Iyer, Sarah Stabenfeldt and Elizabeth Cosgriff-Hernandez introduce the J. Mater. Chem. B themed issue in honor of Shelly Sakiyama-Elbert's 50th birthday: celebrating 25 years of shaping biomaterials in neuroengineering.
Correction for 'The long-term behaviors and differences in bone reconstruction of three polymer-based scaffolds with different degradability' by Jinhui Huang et al., J. Mater. Chem. B, 2019, 7, 7690-7703, https://doi.org/10.1039/c9tb02072a.
Liquid-liquid phase separation (LLPS) is a ubiquitous physicochemical phenomenon that has garnered significant attention in the fields of biomaterials and soft matter science in recent years. Synthetic polymer systems, owing...
Diabetic wounds are persistently exposed to oxidative stress and impaired angiogenesis, resulting in delayed wound closure and compromised repair quality. Proanthocyanidins (PAC) exhibit favorable antioxidant activity; however, their insufficient aqueous dispersion stability and limited local bioavailability restrict their application in chronic wound repair. In this study, PEG-stabilized proanthocyanidin nanoparticles (PPN) were fabricated through a mPEG-SH mediated weakly alkaline oxidative assembly strategy and subsequently incorporated into commercial collagen sponges to prepare a composite dressing (CBS-PPN). Compared with PAC, PPN exhibited a more stable particle size distribution, improved cytocompatibility, and a more homogeneous distribution within the sponge. Further investigations demonstrated that CBS-PPN attenuated oxidative stress-induced damage and enhanced HUVEC tube formation in vitro. Transcriptomic analysis indicated that CBS-PPN regulated fibroblast repair-related processes, including cell adhesion, matrix remodeling, and stress injury responses, and may provide indirect support for a pro-angiogenic repair microenvironment. In a diabetic rat full-thickness skin defect model, CBS-PPN accelerated wound closure and promoted re-epithelialization, collagen deposition, and neovascularization. In summary, PEG-stabilized nanoparticle assembly improved the dispersion stability of PAC and its distribution within the collagen sponge, thereby enhancing their antioxidant and pro-repair effects. This study provides a new strategy for the development of natural polyphenol-based diabetic wound repair materials.
Immunotherapy has rapidly emerged as the new pillar of cancer treatment alongside surgery, radiotherapy and chemotherapy. However, existing immunotherapeutic approaches face significant limitations such as inefficient tumor-targeted drug delivery, poor cellular internalization and off-target effects, all of which lead to suboptimal therapeutic outcomes. Recent advances in nanotechnology have introduced nanomedicines as a promising solution to these challenges, which can precisely deliver immunomodulators, enhance antigen presentation, and increase T-cell infiltration as well as improve their targeting and safety, and thus powerfully enhance the therapeutic effect of tumor immunotherapy. Among numerous types of nanomedicines, biodegradable nanomaterials have recently received extensive attention for tumor immunotherapy due to their unique advantages including biodegradability, simple and cost-effective synthesis, and use of renewable resources, aligning with environmental and sustainable development goals. More importantly, many biodegradable nanomedicine platforms, such as liposomes, polymeric micelles and polymeric nanoparticles, have already entered clinical trials or received approval. Thus, the biodegradable nanomaterials exhibit promising potential for tumor immunotherapy. However, comprehensive reviews systematically summarizing the application of biodegradable nanomaterials for tumor immunotherapy are still rare. Herein, this review provides a detailed introduction to this field. Firstly, the general types of biodegradable nanomaterials for tumor immunotherapy are introduced. Secondly, the common mechanisms of tumor immunotherapy are elucidated. Thirdly, the basic research applications of biodegradable nanomedicine-mediated tumor immunotherapy are emphasized. Next, the clinical transformation prospects of biodegradable nanomaterials for tumor immunotherapy are highlighted. Furthermore, the potential impacts of degradation behaviors on the immune microenvironment are pointed out. Finally, the challenges and future outlooks are discussed.
Radiation-induced skin injury (RISI) poses a significant clinical challenge, with its core pathology involving epidermal barrier disruption caused by excessive reactive oxygen species (ROS) accumulation, oxidative stress, and cell apoptosis. However, effective local treatment options for RISI remain highly limited. Therefore, we developed a phase-transition hydrogel microneedle system loaded with keratin nanoparticles (KNPs@M/G MNs) for the multi-target combinatorial therapy of RISI based on a physical phase-transition mechanism. Specifically, these microneedles penetrate the stratum corneum to precisely deliver therapeutic agents to the epidermis. They rapidly undergo gelation in the skin and release the drugs in a programmed manner: mangiferin is initially released to scavenge radiation-induced ROS, thereby preventing oxidative DNA damage. Subsequently, KNPs are released in a sustained manner to inhibit the inflammatory response via modulation of the nuclear factor kappa B (NF-κB) pathway, maintain cell viability through anti-apoptotic effects, and upregulate cytokeratins (K) 14 and 17, thereby promoting barrier reconstruction and hair follicle regeneration. Collectively, the KNPs@M/G microneedle system exerts therapeutic effects through early-stage antioxidative protection followed by later-stage anti-inflammatory, anti-apoptotic, and pro-regenerative activities, presenting an innovative strategy for the treatment of RISI.
The major challenge in infected bone defect repair is the difficulty in achieving infection control and bone regeneration simultaneously. In this study, a 3D-printed polylactic acid/magnesium (PLA/Mg) composite scaffold loaded with chitosan-chlorhexidine gluconate (CTS-CHG) microspheres was developed, and its antibacterial, osteogenic, and biosafety properties were systematically evaluated. CTS-CHG microspheres were prepared by ionic crosslinking and immobilized onto porous PLA/Mg scaffolds. The morphology, physicochemical properties, drug release behavior, antibacterial activity, cytocompatibility, osteogenic performance, and preliminary in vivo biosafety of the scaffold were then assessed. The results showed that the PLA/Mg/CTS-CHG scaffold possessed a stable porous structure, suitable mechanical strength, and sustained release profiles of Mg2+ and CHG. Compared with the PLA and PLA/Mg groups, the composite scaffold exhibited markedly enhanced antibacterial activity, with a stronger inhibitory effect against Staphylococcus aureus than against Escherichia coli. Meanwhile, the scaffold maintained good cytocompatibility and did not show evidence of compromising the osteogenic advantage observed in the PLA/Mg scaffold. In vivo, the PLA/Mg/CTS-CHG scaffold showed improved bone repair under infected conditions, which may have been associated with its antibacterial performance. Zebrafish and rat evaluations further showed no obvious short-term abnormalities in oxidative stress-related signals, inflammatory cell-associated signals, developmental morphology, or major organ histology. In conclusion, the PLA/Mg/CTS-CHG scaffold integrated enhanced antibacterial capability with preserved osteogenic performance and represents a promising multifunctional scaffold for infected bone defect repair.
Fungal keratitis (FK) is a severe ocular infection that often leads to vision impairment, yet its clinical management remains challenging due to poor drug bioavailability from conventional eye drops and tissue damage risks associated with intraocular injections. Microneedles (MNs) offer a minimally invasive alternative for corneal drug delivery, but conventional designs cause pain, structural damage, and reduced corneal transparency. Herein, we report a finite element simulation-assisted strategy to fabricate personalized curved-backing microneedles with a curvature-matched backing that ensures conformal surface contact, controlled penetration depth, and uniform drug distribution, effectively overcoming the limitations of conventional MNs. To enhance drug delivery, amphotericin B, a hydrophobic antifungal agent, was encapsulated in poly(lactic acid) nanoparticles, achieving improved solubility and sustained release. In vitro and in vivo short-term evaluations demonstrated that this integrated system effectively inhibited C. albicans growth and promoted corneal repair in a rabbit model of FK, without inducing significant ocular irritation or structural damage over the 14-day observation period. Our design strategy offers a viable approach to addressing barriers associated with corneal drug delivery.
The growing threat of antimicrobial resistance makes rapid and sensitive detection of bacterial pathogens in human samples an urgent need. In the case of blood infection, or bacteremia, standard pathogen...
