ACS Applied Bio Materials最新文献

Wearable biosensors are an emerging field in the area of health monitoring, and when they combine with various biopolymers, they provide affordable, sustainable, noninvasive, and real-time monitoring of health. Natural biopolymers such as silk, cellulose, and chitosan offer great potential in the fabrication of these biosensors because of their various properties, such as biocompatibility, flexibility, biodegradability, hydrophilicity, and renewability. These biopolymer-based wearable biosensors provide continuity and comfort with high precision in monitoring health in less time. This Account explores how the remarkable structural and physicochemical properties of these biopolymers support their fabrication and integration into wearable biosensors that can withstand the dynamic environment of the human body. Leveraging these biopolymers enables the development of eco-friendly and skin-conformable biosensors for glucose, lactate, and other biofluids including saliva, sweat, tears, and other interstitial fluids. These biopolymers are of significant importance in the domains of personalized medicine, enhancing athletic performance tracking, and chronic disease management for next-generation wearable devices.

The programmed polarization of macrophages, which exhibit remarkable plasticity from pro-inflammatory (M1) to anti-inflammatory (M2) phenotypes, serves as a key driver of skin wound healing. However, dysregulated macrophage polarization toward a dominant M1 phenotype can induce excessive inflammation and hinder wound healing. Current therapeutic strategies to promote M2 polarization, such as cytokines, anti-inflammatory drugs, and stem cell therapies, have limited effectiveness, complex manufacturing processes, and potential toxicity. Here, we report the development of mannose- and sulfonic acid-modified silk fibroin (SF) that are bioactive and promote M2 polarization by activating the MR-ERK/STAT6 signaling axis. In vitro studies showed increased expression of CD206 and anti-inflammatory gene markers, confirming their ability to regulate macrophage polarization without additional therapeutic agents. Moreover, the mannose- and sulfonic acid-modified SF films, used as wound dressings, enhanced wound healing by promoting M2 macrophage polarization, angiogenesis, collagen deposition, and wound closure. These findings highlight the potential of chemically modified SF as bioactive materials for immune modulation and tissue regeneration.

Multifunctional silk fibroin (SF) nanofibrous membranes incorporating cuttlefish ink (CI) and vitamin B2 (VitB2) were developed via water-based electrospinning as bioactive scaffolds for soft tissue regeneration and laser-assisted tissue welding. CI provided antioxidant and photothermal properties, while VitB2 promoted cellular proliferation. Membranes exhibited controlled VitB2 release and CI retention within the matrix. NIH-3T3 fibroblast assays confirmed high viability (>80% at 48 h), with CI promoting adhesion and cytoskeletal organization, and VitB2 enabling formation of a confluent, organized cell layer. Laser-assisted welding produced satisfactory adhesion and shear-stress resistance on the order of ten kPa in ex vivo tendons, corneas, and sclerae, while keeping tissue temperatures below the 60 °C threshold for thermal damage. These findings highlight CI- and VitB2-loaded SF membranes as sustainable, cytocompatible scaffolds with antioxidant and adhesive functionalities, offering a versatile platform for soft tissue repair via an adhesive-free approach.

Malignant melanoma has a high recurrence rate after surgical resection, conventional neoadjuvant chemotherapy (NAC) suffers from off-target toxicity and limited efficacy. Leveraging elevated tumor-specific reactive oxygen species (ROS), we designed a sequential therapeutic strategy combining ROS-responsive micelles and a multifunctional hydrogel to combat local recurrence. By conjugating 3-indoleacetic acid to chondroitin sulfate via a ROS-responsive thioketal linker, an amphiphile (CS-TK-IAA, CTI) was synthesized, significantly enhancing tumor-specific uptake and ROS-scavenging capacity. CTI self-assembled into micelles (CLT@CTI) encapsulating celastrol (CLT), achieving high encapsulation efficiency (92.3%) and drug loading capacity (25.2%). Postoperatively, an injectable chitosan-based hybrid hydrogel (CPG) with self-healing, tissue adhesion, and hemostatic properties was applied to the resection site, triggering a photothermal effect via near-infrared light. In a mouse melanoma recurrence model, neoadjuvant CLT@CTI therapy effectively suppressed primary tumor growth, while postoperative CPG gel-mediated photothermal ablation of residual tumors dramatically delayed recurrence and improved 60-day survival rates. This sequential therapeutic regimen, neoadjuvant chemotherapy with postoperative photothermal therapy, provides a promising and viable solution for preventing melanoma recurrence.

The emergence of antibiotic-resistant bacteria has rendered conventional antibiotic treatments ineffective, necessitating the development of antibacterial agents with unique mechanisms of action. To address this challenge, researchers have increasingly resorted to synthetic and bioengineered nanomaterials to augment the antibacterial activity of nonantibiotic antibacterials (nonantibiotic antibacterial agents), including antimicrobial peptides (AMPs), metallic nanoparticles (MNPs), bacteriophages (phages), and phage derivatives such as endolysins, which are under extensive investigation. In this review, we discuss how modifications and syntheses of these agents, leveraging advancements in nanoscience and nanotechnology, have and can significantly enhance their antibacterial properties and overcome limitations such as cytotoxicity, instability, and poor bioavailability for in vivo or clinical use. Furthermore, we highlight supramolecular strategies for improved delivery, including phage-based, AMP-based, and endolysin-based systems and their demonstrated efficacy against persistent bacterial infections. Additionally, we highlight how the integration of artificial intelligence and machine learning ultimately promises to revolutionize the design, optimization, and clinical translation of these precision antimicrobials, paving the way for targeted and highly effective treatments.

Quercetin (Que) and naringenin (Nar) are natural compounds with potent antioxidant and anti-inflammatory activities, showing promise for alleviating ultraviolet B (UVB)-induced skin photoaging. The presence or absence of a C═C bond in the C-ring defines whether the compound is a flavonol or a flavanone. To overcome poor water solubility and low bioavailability of the two flavonoids, we prepared inclusion complexes using β-cyclodextrin (β-CD), hydroxyethyl-β-cyclodextrin (HE-β-CD), and hydroxypropyl-β-CD (HP-β-CD). These complexes leverage the cyclodextrins’ hydrophilic exterior and hydrophobic interior to encapsulate Que and Nar, respectively. Through integrated analyses─including molecular docking, phase solubility studies, characterization (UV, Fourier-transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and NMR), solubility tests, and antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH)) assays─we systematically elucidated the structure–activity relationships of these flavonoid–cyclodextrin interactions. The therapeutic potential was further evaluated in a UVB-induced mouse model of skin photoaging. Results confirmed the spontaneous formation of stable 1:1 molar ratio inclusion complexes between the flavonoids and cyclodextrins. The enhancement of complex stability, water solubility, and antioxidant activity consistently followed the order: HP-β-CD > HE-β-CD > β-CD. Owing to Que’s conjugated planar structure, it exhibited weaker binding to β-CD than did Nar. However, Que formed more stable complexes with HE-β-CD and HP-β-CD than Nar did. In vivo, the Que/HP-β-CD complex demonstrated superior efficacy, most effectively reducing malondialdehyde (MDA) levels, alleviating epidermal hyperplasia, and increasing collagen fiber content. Furthermore, the inclusion complexes amplified the regulatory effects of Que and Nar on mitogen-activated protein kinase (MAPK) and TGF-β/Smad pathways: they enhanced the downregulation of p-p38 and MMP-1 to inhibit collagen degradation and promoted the upregulation of Smad2/3 and COL1A1 to stimulate collagen synthesis. In conclusion, the β-cyclodextrin inclusion complexes of flavonoids, designed based on structure–activity relationship studies, significantly improve the compounds’ solubility, stability, and bioactivity. This leads to enhanced protective efficacy against UVB-induced photodamage through the concurrent modulation of multiple signaling pathways.

Infectious wound healing remains a significant medical challenge due to Staphylococcus aureus (S. aureus) colonization. The development of nano-Chinese herbal medicines has provided new approaches for the application of nanomedicines. Extracellular vesicles (EVs) play an important role as mediators of bacterial communication. However, the roles of Chinese herbal medicine-derived EV in S. aureus physiology and ecology have not been characterized. Furthermore, developing effective CHM-EV-based therapies for managing bacteria-infected wounds remains challenging. In this study, we found that S. aureus was specifically killed by EV derived from the traditional Chinese medicine pomegranate peel (PTP-EV). Furthermore, PTP-EV was taken up into S. aureus and could alter the expression of approximately 46.53% of all genes in the S. aureus genome, influencing diverse functions such as replication, division, and metabolism. Notably, PTP-EV downregulated the genes of key virulence factors, including saeS, saeR, and psmB. Incorporating PTP-EV into the GelMA (PEV-GM) hydrogel effectively promoted sustained slow release of EV. Furthermore, the PEV-GM hydrogel demonstrated strong antibacterial activity against S. aureus, thereby accelerating the wound healing process. Our findings offer information about the physiological and ecological significance of PEV-GM-bacterial interactions and the therapeutic potential of PEV-GM hydrogel as a promising and biocompatible dressing for managing biofilm-associated chronic wounds.

The quantitative monitoring of neurofilament light chain (Nf-L) is critical for the early diagnosis and prognosis of neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), yet achieving femtomolar sensitivity in a portable, label-free format remains a formidable challenge. Here, we report a high-performance organic electrochemical transistor (OECT) immunosensor engineered via the precise template-free electropolymerization of a dual-functional poly(EDOT-COOH-co-EDOT-EG3) copolymer. By systematically modulating the polymerization kinetics, we elucidated a decisive structure-function relationship governing biosensing efficacy: while microstructured channels formed at longer deposition times exhibited superior intrinsic transconductance due to maximized volumetric capacitance, the optimized nanotubular architecture provided the ideal balance of open porosity and accessible surface area. This specific nanotopography facilitated a significantly higher density of covalent antibody immobilization compared to its microstructured counterpart, thereby dominating the signal transduction mechanism through enhanced dielectric barrier formation upon antigen binding. Capitalizing on this morphology-governed sensitivity, the platform achieved a theoretical limit of detection (LOD) of 0.062 fg/mL (3σ criterion) and a rigorous LOD of 32.77 fg/mL (Hubaux-Vos method) across a broad dynamic range, along with exceptional selectivity and operational stability over 500 cycles. These findings underscore the critical role of precision channel engineering in bioelectronics, establishing a robust, lithography-free pathway for next-generation point-of-care diagnostics targeting diseases.

Impaired macrophage polarization is one of the primary factors that hinders the healing of chronic wounds. A bioinspired hydrogel comprising amidated pectin (AmPT) and dialdehyde carboxymethylcellulose (DCMC) reinforced with honey was reported for wound healing. Pectin was obtained from orange peels via microwave-assisted extraction and further subjected to amidation. The hydrogels were constructed by the Schiff base reaction between the amino groups of AmPT and the aldehyde groups of DCMC. The hydrogels incorporated with the highest honey content, i.e., HH3 hydrogel, exhibited higher thermal stability, tensile strength, and anti-inflammatory and antioxidant properties. A controlled release drug profile for curcumin was evidenced in the colorectum from the HH3@Cur hydrogel, and the release kinetics indicated the anomalous nature of release. An enhanced migration and proliferation of 3T3 fibroblasts was marked for HH3@Cur. The wound closure was noted at almost 92% for the HH3@Cur hydrogel after 24 h. The q-PCR analysis revealed that the expressions of IL-4, IL-13, and PPAR-γ were upregulated in the HH3@Cur-treated group, indicating that it efficiently promoted macrophage transition from pro-inflammatory M1 to anti-inflammatory M2 phenotypes associated with improved wound repair. Furthermore, the HH3@Cur hydrogel was explored for microtissue formation and wound healing application using a zebrafish model, which aligned with in vitro data. Herein, by 16 dpw, the wound closure rate marked to 92.8% for HH3@Cur hydrogel in comparison to the control group (71.5%), and the mean mRNA expressions of IL-4, IL-13, and PPAR-γ were upregulated accordingly. Overall, the results indicated that HH3@Cur hydrogel ameliorates wound healing by influencing the expression of biomarkers related to inflammation, macrophage polarization, and angiogenesis.

Synthetic biomaterials with osteoconductive or osteoinductive capabilities continue to evolve in functionality and expand their potential as viable substitutes for bone autografts. Recent developments with nanomaterial lattices have seen scaffold systems, especially brittle calcium phosphates, optimized for biological and mechanical performance. The addition of 2D atomic layers of carbon (graphene) to ceramic scaffolds is a well-studied avenue that potentially improves strength, functionality, and osteogenic potency; however, concerns of poor bioresorption and concentration-dependent toxicity have limited their translational value. The recent discovery of hematene, an ultrathin 2D nanosheet of iron oxide (Fe₂O₃) with its unique physiochemical properties and potential to be bioresorbable, could present a promising opportunity. In this work, exfoliated ultrathin hematene nanosheets were incorporated into porous monetite implants. In vitro testing with MC3T3-E1 preosteoblasts showed that hematene-loaded scaffolds supported cell infiltration and adhesion with a 24% increase in proliferative activity. The activity of the bioscaffold on cell proliferation and differentiation was evaluated. Findings showed that hematene-loading significantly improved the mechanical compression performance of monetite cements by 20%, without impacting degradation profiles. Furthermore, hematene loading significantly enhanced the osteogenic potency of monetite scaffolds with heightened bone biomarker expression levels of ALP, RUNX2, and SPARC. This preliminary report uncovers the therapeutic potential of hematene derivatives for the first time, particularly as a promising scaffold for bone repair.