Biomaterials Science最新文献

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.

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.

Endosomal escape is a limiting factor for the in vivo application of nucleic acid therapeutics and remains a major challenge in the development of drug delivery systems. In this study, we developed a pH-ultrasensitive membranolytic polymer (P(C6-Bn_X))-assisted delivery system (NP_BnX) to facilitate siRNA endosomal escape and enhance the gene silencing efficiency. The incorporation of P(C6-Bn_X) imparts the siRNA delivery system with enhanced cellular uptake, effective membranolytic activity under endosomal pH conditions, and improved endosomal escape efficiency of siRNA. The significantly enhanced siRNA-mediated gene silencing efficacy was also confirmed in multiple tumor cell lines. Further investigations demonstrated that the delivery of siRNA targeting CD47 via this system effectively suppressed the expression of CD47 at both the cellular level and in vivo, thereby enhancing macrophage-mediated phagocytosis of tumor cells and promoting anti-tumor immune responses. This study provides a promising and viable strategy for the design and development of siRNA delivery systems.

Chemotherapy remains a primary cancer treatment. However, the poor selectivity of conventional small-molecule chemotherapeutic agents often leads to severe side effects against normal cells and tissues, limiting their clinical application. To address this challenge, tumor-microenvironment-activated prodrugs represent a promising strategy for enhancing selectivity and efficacy. Herein, we developed a charge-reversal prodrug, PIX-DMMA, synthesized through the reaction between primary amino groups of pixantrone (PIX) and 2,3-dimethylmaleic anhydride (DMMA). PIX-DMMA is activated under tumor extracellular pH (∼6.5), releasing the o-PIX while simultaneously undergoing charge reversal from negative to positive, thereby enhancing cellular uptake. Drug release kinetics at pH 6.5 were verified via NMR spectroscopy. In vitro studies demonstrated that prodrug activation at pH 6.5 confers significant tumor selectivity and potent cytotoxicity toward cancer cells. Furthermore, in vivo studies in LoVo tumor-bearing mice showed significant tumor growth inhibition without significant systemic toxicity. This acid-triggered charge-reversal prodrug represents a promising strategy for selective cancer therapy.

To overcome therapy resistance driven by breast cancer stem cells (BCSCs) and the systemic toxicity of conventional chemotherapy, we engineered a multi-stimuli-responsive nanoprodrug (DT/PAC@AI NPs) implementing a "chemo-differentiation-cancer stem cell inhibition" strategy. This system co-delivers irinotecan (IRI), all-trans retinoic acid (ATRA), and CPUL119 via (1) a hypoxia-responsive prodrug (PAC: PEG_2k-Azo-CPUL119) and (2) a pH/esterase-responsive conjugate (AI: ATRA-IRI). The targeted NPs (90-130 nm), modified with DSPE-PEG_2k-Try for LAT1-mediated uptake, demonstrated tumor microenvironment-triggered drug release: rapid PAC release under hypoxia and enhanced AI release at pH 5.0/esterase. In vitro, DT/PAC@AI NPs showed 20% higher cellular uptake and potent cytotoxicity against MDA-MB-231 cells (IC₅₀ = 4.77 ± 0.32 µM vs. free drugs: IRI, 23.17 µM; CPUL119, 9.27 µM; ATRA > 50 µM), inducing 3.7-fold more apoptosis (32.6% vs. 8.7%). Critically, they reduced CD44⁺/CD24^- BCSCs by 13.7% and inhibited tumor sphere formation by 87.6%. In vivo, they achieved optimal tumor suppression and BCSC elimination in xenografts with negligible systemic toxicity. This nanoprodrug platform offers straightforward synthesis, high drug-loading capacity, and potent dual-action efficacy against bulk tumor cells and BCSCs, presenting a promising advanced breast cancer therapy.

Nitric oxide (NO) is a versatile gaseous signaling molecule with broad therapeutic potential in cardiovascular regulation, immune modulation, oncology, antibiotics, and tissue regeneration. However, its clinical application is severely constrained by physicochemical limitations, including poor aqueous solubility, rapid degradation, and the lack of spatiotemporal control over its release. To address these challenges, a diverse array of NO donors, ranging from spontaneous-release compounds to stimuli-responsive prodrugs, has been developed, each with distinct advantages and limitations. In this review, we classify representative NO donors into two major categories: unstable donors (e.g., N-diazeniumdiolates, S-nitrosothiols, SIN-1) and stable donors (e.g., O²-protected diazeniumdiolates, protected SIN-1, nitrobenzene derivatives, BNN6). Here, we highlight recent advances in the engineering of delivery platforms, including polymeric nanoparticles, hydrogels, xerogels, liposomes, and various inorganic materials, which enable precise, stimuli-triggered NO release, improved stability, and tissue-specific targeting. By integrating NO donor chemistry with materials design, these platforms offer strong potential for controlled NO-based therapies across a wide range of biomedical applications. We conclude by outlining future directions and key challenges in translating NO delivery systems into clinically viable therapeutics.

Prolonged indwelling of ureteral stents often leads to encrustation, which can cause functional failure and poses a significant clinical challenge. Zwitterionic polymers exhibit excellent anti-fouling performance due to their strong surface hydration. Inspired by this, a multifunctional hydrogel coating based on a trimethylamine N-oxide zwitterionic polymer was developed for polyurethane stents to mitigate encrustation. The coating was fabricated using an innovative approach that combines a superwetting-assisted interfacial polymerization strategy with dip coating technology, significantly improving the adhesion strength between the coating and the stent surface to ensure long-term stability. Notably, the coating strongly interacts with water molecules to form a robust hydration layer, effectively inhibiting bacterial adhesion. In a 90-day simulated urinary flow test, the coating demonstrated outstanding anti-encrustation performance, reducing encrustation by 92%, while maintaining excellent biocompatibility. This coating technology provides an effective and durable solution for preventing complications associated with ureteral stents and shows broad application potential in the field of urological medical devices.

The emergence of multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) infections, particularly those involving biofilm formation, poses a critical challenge to global healthcare. While polymyxin B (PMB) remains a last-line antibiotic against such infections, its efficacy is severely limited by poor biofilm penetration and adaptive resistance mechanisms. In this study, we developed a biomimetic nanoplatform (PMφ-PLGA-NOR) comprising a poly(lactic-co-glycolic acid) (PLGA) core loaded with norharmane (NOR), coated with PMB-modified P. aeruginosa cytoplasmic membrane (PMφ). This design utilizes the homologous targeting of bacterial membrane components and PMB's affinity for Gram-negative pathogens to achieve efficient biofilm penetration. NOR, a β-carboline compound, has been shown to disrupt quorum sensing (QS) by inhibiting PqsA, resulting in significant reduction in biofilm formation. In vitro investigations have demonstrated that PMφ-PLGA-NOR disrupts the integrity of biofilms, thereby enhancing the bactericidal efficacy of PMB by facilitating its deep penetration into the biofilm matrix. In vivo, intraperitoneal administration of Mφ-PLGA-NOR combined with PMB achieved a 2-log reduction in bacterial lung burden. This study underscores the promise of bacterial plasma membrane-based pathogen-mimetic nanoplatforms in potentiating the efficacy of antibiotic adjuvants in conjunction with biofilm-penetrating strategies.

DNA, the fundamental carrier of genetic information, has evolved beyond its biological function to serve as a versatile and programmable material for constructing nanoscale architecture. This review presents a comprehensive overview of the chemical and enzymatic strategies that enable the synthesis, ligation, and assembly of DNA nanostructures, highlighting their interdisciplinary impact. We first examine key chemical approaches, including oligo synthesis and DNA origami, which offer precise control over base sequence and structural complexity. We then explore enzymatic methods—such as ligation and amplification techniques—that facilitate high-fidelity and scalable construction of intricate nanostructures. Subsequently, we investigate how these strategies are applied to create DNA-based materials such as chips, hydrogels, and reconfigurable architectures for in vitro biosensing and other biomedical applications. The review further delves into enzymatic assembly in vivo, including drug delivery, bioimaging, molecular machines, and therapeutic interventions. Finally, we highlight emerging frontiers of DNA nanotechnology, particularly its integration into nanoelectronics and its transformative potential as a medium for digital data storage. By addressing recent advances, current challenges, and future perspectives, this review underscores the pivotal role of chemical and enzymatic techniques in advancing DNA nanotechnology as a foundational platform for next-generation biomedical, materials, and information technologies.

Molecularly imprinted polymers (MIPs) have emerged as robust synthetic alternatives to natural biorecognition elements, offering high selectivity and stability for sensor applications. Advancements in nanotechnology and polymer chemistry in the last few decades positioned MIPs as emergent and promising materials for sensor devices. This review covers various components of a functional MIP structure, including monomers, cross-linkers, and initiators that form the MIP backbone, aided by template molecules and porogens. Chemical interactions involved in polymer imprinting, to critically understand how the various components interact with each other to make functional MIP structures, have been discussed in detail using suitable examples. The different methods of polymerization used to formulate its functional version have also been elaborated in the current article, which includes bulk polymerization, surface polymerization, electro-polymerization, sol–gel, phase inversion, and epitope imprinted polymerization, discussed in detail using suitable examples. This paper also includes precise yet insightful discussions on MIP-based sensing of various molecular categories, viz. small molecules, macromolecules, and environmental pollutants. The tables cover details of sensor fabrication strategies, their limits of detection (LOD) and linear dynamic range (LDR), and the technique used along with the real sample considerations in those studies. The paper brings fundamental insights from synthesis to real-time applications of these materials in order to understand their overall research scope along with translational bottlenecks in a future perspective.