ACS Biomaterials Science & Engineering最新文献

Effective treatment of ocular inflammation is hindered by limited drug uptake and rapid clearance, resulting in poor bioavailability and frequent dosing of conventional eye drops. To improve drug retention and bioavailability, we designed and manufactured electrospun mucoadhesive nanofibers based on modified mussel foot protein (mMefp-3). Their composition and small diameter (≈250 nm) provide a high surface area, enabling rapid water uptake and in situ gelation on the ocular surface. SEM, light, and fluorescence microscopy confirmed homogeneous, smooth, and bead-free fibers. Ocular residence studies demonstrated prolonged retention and a shift from first-order to zero-order clearance kinetics. In vitro cell culture assays with fibroblasts, and corneal epithelial cells confirmed the biocompatibility of mMefp-3 loaded nanofiber constructs. These findings demonstrate that mMefp-3 incorporation enhances ocular drug residence while maintaining biocompatibility, making these nanofibers a promising ocular drug delivery system.

Surface-associated and device-related bacterial infections require materials that can both eliminate pathogens and prevent microbial colonization. However, antibacterial activity in solution and antifouling performance at interfaces are governed by distinct physicochemical principles, making their integration within a single material challenging. Here, we report a modular bottlebrush polymer (BBP) platform that decouples these functions through architectural design. A library of seven BBPs with monoblock and ABA triblock architectures was synthesized to independently control side-chain charge distribution and interfacial hydration. Multivalent cationic side chains promoted efficient bacterial killing in solution, whereas hydrated PEG or zwitterionic bottlebrush layers anchored by cationic termini formed stable antifouling coatings. In diabetic mice, the BBPs showed no evidence of local irritation, systemic toxicity, or impaired wound healing. In an infected wound model, bactericidal BBPs reduced bacterial burden, while antifouling BBPs suppressed local inflammation. Their combined application improved therapeutic outcomes, demonstrating the benefit of a functionally decoupled strategy. Collectively, these findings establish a generalizable architectural framework for designing multifunctional anti-infective materials.

Herbs possess a long history of medicinal use and abundant pharmacological activities. However, the inherent limitations of their poor bioavailability often restrict their therapeutic efficacy. In recent years, carbon dots (CDs) have shown great potential in biomedical applications owing to their excellent optical properties, good biocompatibility, low toxicity, and small size. Using herbs as precursors to prepare CDs can preserve the "multicomponent, multitarget" characteristics of the crude herbs, enhance and transform their functions through nanoscale effects, offering unique advantages in biomedicine. Quantitative analysis of 121 entries reveals that herb-derived CDs typically exhibit particle sizes of 1-6 nm (mean ≈ 3.4 nm), quantum yields up to 0.67 (mean ≈ 0.11), and broad emission tunability (400-730 nm), with 51 reports including in vivo biosafety testing, all of which showed no obvious toxicity. Based on the latest advances in herb-derived CDs, this review focuses on precursor selection, pretreatment, and synthesis methods. Furthermore, it discusses their applications in biomedicine, bioimaging, and sensing in detail. Finally, a summary and outlook for this significant and promising field are provided. We hope that this review will offer valuable insights for researchers developing herb-derived CDs and contribute to the ongoing modernization and sustainable development of traditional Chinese medicine.

Scaffold-based bone tissue engineering (BTE) represents a pivotal strategy in regenerative medicine, offering substantial promise for repairing damaged bone. These scaffolds provide essential structural support and promote new bone formation by mimicking the native extracellular matrix (ECM). The rational design of an ideal scaffold requires careful balancing of biomaterial properties with biomechanical performance. Natural polymers have gained considerable attention in this context due to their inherent bioactivity, biocompatibility, and tunable mechanical properties. Their key advantage lies in their ability to replicate the complex architecture and function of bone ECM, thereby facilitating cellular interactions and tissue ingrowth. Recent progress in the processing and assembly of natural polymers has enabled innovative scaffold designs, including hydrogels as well as fibrous and porous architectures. These advances allow for the fabrication of scaffolds with precisely tailored features, such as optimal stiffness, controlled pore sizes, and surface topographies conducive to cell adhesion and differentiation. Furthermore, degradation kinetics can be adjusted to match the rate of new tissue formation. This review provides a comprehensive examination of the role of natural polymers in BTE. It critically discusses state-of-the-art fabrication techniques and highlights the critical physicochemical and biological properties that determine scaffold performance. By consolidating these key aspects, the review aims to identify current challenges and outline future directions for the development of natural polymer-based scaffolds. Ultimately, this work seeks to offer practical guidance for the rational design and translational advancement of these materials in bone regeneration.

Nanoparticles encapsulating therapeutic RNA have emerged as a transformative strategy in precision medicine, enabling a wide range of applications such as gene therapy for rare diseases, the silencing of toxic gene products, and the mobilization of the immune system to induce specific responses ranging from immune tolerance to fighting tumors. However, most current preclinical and clinical efforts rely on non-targeted delivery systems, limiting their safety, therapeutic efficacy, and selectivity. To enhance the therapeutic index of RNA-based therapeutic systems, we report on the design of a novel Clec9A-targeted polymeric nanoparticle aimed at exploring strategies to enhance delivery toward CLEC9A-expressing immune cells as a proof of concept in the field of mRNA vaccination. We began by evaluating in silico the binding potential of the previously reported 12-amino-acid WH peptide, known for its high affinity to mouse Clec9A, the human ortholog. Using computational tools, we designed and screened truncated variants of the peptide and identified promising candidates with retained, or even enhanced, binding capacity to human Clec9A. These optimized short peptides were synthesized and covalently conjugated to our proprietary poly(beta-amino ester) (pBAE) polymers. We evaluated the impact of the conjugation site on receptor targeting by comparing terminal versus lateral chain attachment. We show that peptide orientation significantly influences transfection efficiency in human THP-1 cells, used as a monocytic robust in vitro model. Additionally, we computationally generated and validated shorter mutant peptide variants with improved Clec9A affinity over the original sequences. Our findings demonstrate that rationally engineered short peptides improve transfection in a human monocytic cell model, which is consistent with the proposed Clec9A-targeting strategy suggested by computational modeling. This strategy lays the groundwork for the next generation of targeted RNA-based (immune)therapeutics, offering improved selectivity and consequent therapeutic potential.

The increase in bacterial infections and the rise in AMR pose a threat to global health. Conventional antimicrobial therapy is limited by inaccurate pathogen identification, off-target effect, and increasing resistance, for which bioorthogonal chemistry offers a promising solution. Bioorthogonal chemistry comprises rapid and selective chemical reactions performed in biological environments with minimal interference with endogenous processes. This technique has been widely used in biomarkers, drug delivery, etc., due to its biocompatibility and targeting ability. In antibacterial applications, metabolic or affinity-based installation of abiotic chemical handles can decouple bacterial recognition from subsequent imaging or therapeutic recruitment. This review summarizes bioorthogonal strategies for bacterial detection, targeted drug delivery, light-responsive therapy, and localized prodrug activation and provides an application-driven framework for selecting reaction pairs. These approaches offer high chemical selectivity, covalent target retention, and modular integration with diverse diagnostic and therapeutic cargos, but their performance remains constrained by bacterial metabolic heterogeneity, reagent stability, tissue and biofilm transport, multicomponent pharmacokinetics, and long-term biosafety. Future progress will depend on faster and more biocompatible reaction design, standardized in vivo evaluation, scalable manufacturing, and clinically practical delivery or activation methods. By linking bacterial chemical labeling with therapeutic recruitment or activation, bioorthogonal chemistry provides a versatile framework for precision antibacterial therapy.

Single-domain antibodies (sdAbs) derived from naive phage display libraries offer a time-efficient alternative to animal immunization but often exhibit suboptimal affinity, particularly for small-molecule haptens, where restricted binding interfaces limit the efficacy of traditional saturation mutagenesis. For instance, the wild-type sdAb (B1)-targeting ethoxyquin (EQ) exhibits a moderate equilibrium dissociation constant (K_D) at the submicromolar level (within the 10⁻⁷ M range), restricting its practical sensitivity. To overcome the structural and energetic barriers inherent in hapten recognition, a “structure-guided directed modification” strategy was developed that focuses on conformational tuning rather than simple side-chain replacement. Integrating AlphaFold2 modeling and AutoDock mechanistic analysis identified key interactions (e.g., the ASP19-EQ-N8 hydrogen bond). Subsequently, a random single-amino acid insertion strategy was implemented within the CDR3 loop (residues 77−90) to fine-tune local loop geometry. Top candidates were screened via MM/GBSA binding free energy calculations and experimentally validated using biolayer interferometry. This approach yielded three high-affinity mutants—77A, 79C, and 85H—with calculated ΔΔG values of −10.56, −4.35, and −6.69 kcal/mol, respectively. The mutants achieved enhanced affinities in the tens-of-nanomolar range (down to 35.1 nM), representing up to approximately 3 times overall improvement. Importantly, orthogonal surface plasmon resonance analysis using nonconjugated, free EQ successfully verified this affinity maturation trend, showing that mutant 79C bound free EQ with a K_D of 1.30 × 10⁻⁵ M (a 2.3 times improvement over wild-type) through simultaneously accelerated association and slowed dissociation. Mechanistically, this substantial increase in affinity is attributed not only to reinforced noncovalent networks that significantly stabilize the complex but also to favorable CDR3 geometric outward flips that alleviate steric hindrance, leading to an approximate 3.8 times acceleration in the k_on. Crucially, these mutants demonstrated notable anti-interference tolerance in complex aquatic food matrices (e.g., sea bass extracts). Ultimately, this work provides a practical and efficient computational framework for assisting the rapid evolution of low-affinity hapten sdAbs into high-performing biorecognition elements with potential for next-generation biosensing architectures.

Triple-negative breast cancer (TNBC) represents the most aggressive form of breast cancer and is associated with the worst prognosis. Ferroptosis holds great promise as an emerging therapeutic strategy; however, TNBC cells demonstrate reduced sensitivity to ferroptosis as a result of elevated mitochondrial membrane potential (MMP), inadequate production of reactive oxygen species (ROS), and the presence of activated antioxidant defencses, making it difficult for lipid peroxidation to accumulate to a lethal threshold. As an emerging therapeutic strategy, sonodynamic therapy (SDT) is particularly suitable for deep-seated tumors due to the excellent tissue penetration capabilities of ultrasound (US). Nevertheless, current sonosensitizer typically experience limited sonodynamic efficacy and inadequate targeting of tumors, whereas small interfering RNA (siRNA) presents a highly promising option for gene therapy, its efficacy is heavily dependent on efficient and safe cellular delivery vectors. Therefore, we designed and synthesized a folate-modified Fe-TCPP metal-organic framework (FTFA) nanoplatform that serves both as a siATAD3A gene therapy carrier and as a sonosensitizer to generate ROS upon ultrasound (US) irradiation. ATAD3A displays high expression levels in TNBC and is linked to a negative prognosis; it's silencing reduces MMPs and increases ROS-induced apoptosis. siATAD3A was loaded onto FTFA to prepare FTFA@siATAD3A, which was delivered to TNBC cells via folate receptor-mediated targeting. Under US irradiation, the Fe³⁺ loaded within this platform synergistically triggers a ferroptosis cascade involving the Fenton reaction, lipid peroxidation, and GPX4 downregulation, effectively inducing ferroptosis. This method greatly reduces the proliferation of cells, as well as their migration and tumor growth when tested in living organisms, and it also shows excellent compatibility with biological tissues. In summary, FTFA@siATAD3A provides a novel strategy for the synergistic gene-ferroptosis therapy of TNBC using sonodynamic effects.

We propose using the electrospray cone-jet mode operated near its minimum-flow-rate stability limit for single-cell deposition. Because the jet is much thinner than the cells themselves, individual cells can be clearly visualized or detected during deposition. At such low flow rates, individual cells could potentially be placed at distinct, user-defined locations, even at relatively high cell concentrations. In this sense, our approach provides a spatial resolution at the scale of a single cell. We demonstrate the method’s capabilities by depositing cells onto a millimeter-scale droplet of a standard cell-culture medium. Cell viability assays indicate that many cells maintain membrane integrity after exposure to the electrosprayed liquid, suggesting that the process can preserve cell integrity in a substantial fraction of cells under the tested conditions.