Biomaterials research最新文献

Bacterial-infected wounds impose a substantial burden worldwide, with polymicrobial infections exacerbating the complexity of healing through dysregulated pH environments and gelatinase-mediated matrix degradation. Herein, we developed a microenvironment-responsive microneedle (MN) patch utilizing a "dynamic warning-graded intervention" strategy. The patch incorporates (a) a bromothymol blue-based pH visual warning system that detects acid-base changes during both acute and chronic infections, (b) a gelatin methacryloyl and exosome matrix material that enables enzyme-triggered release of human bone marrow mesenchymal stem cell-derived exosomes, responding to pathological gelatinase for spatiotemporal drug delivery, and (c) triple therapeutic payloads [hemostasis (halloysite nanotubes)/antibacterial and anti-inflammatory (antimicrobial peptides)/scar reduction (salvianolic acid B)]. In vitro validation demonstrated a bacterial clearance rate exceeding 95% against methicillin-resistant Staphylococcus aureus/imipenem-resistant Pseudomonas aeruginosa, with biofilm inhibition and disruption rates both surpassing 90%. In vivo experiments demonstrated that MNs showed observable changes in wound color within 8 h in both infectious acute and chronic wounds. In acute wounds, nearly complete healing was achieved within 10 d. By coordinating hemostasis (platelet activation within 60 s), controlling inflammation (62.07% down-regulation of tumor necrosis factor-α), and promoting angiogenesis (2.51-fold up-regulation of CD31), the healing rate of diabetic ulcers was accelerated by 9.20% compared to clinical dressings. This platform provides a foundation for integrating real-time diagnosis and treatment in complex wound management.

Colorectal cancer (CRC) remains a major clinical challenge owing to its immunosuppressive tumor microenvironment and limited targeting therapeutic efficiency. Developing innovative strategies that integrate immune activation with enhanced tumor-targeting ability is urgently needed. Herein, we reported a bioengineered exosome drug delivery nanoplatform (Apatinib-Exo^aPD-L1), in which HEK293T-derived exosomes were surface functionalized with anti-PD-L1 antibody (aPD-L1) and encapsulated the tyrosine kinase inhibitor Apatinib, aiming to enhance the tumor-targeted immunotherapy against CRC. Apatinib-Exo^aPD-L1 exhibited efficient tumor-targeting capability and prolonged systemic circulation, attributed to aPD-L1 modification, resulting in markedly enhanced antitumor efficacy without evident body toxicity. Mechanistically, Apatinib was efficiently delivered and internalized by tumor cells, where it triggered immunogenic cell death (ICD) and promoted dendritic cell maturation. This immune activation cascade facilitated the infiltration and activation of cytotoxic T cells within the tumor microenvironment. Furthermore, Apatinib-Exo^aPD-L1 reduced the population and suppressive function of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), thereby effectively reversing immune suppression and amplifying the antitumor immune response. Collectively, our findings demonstrated that Apatinib-Exo^aPD-L1 is a safe and effective exosome-based therapeutic platform, offering a promising strategy to convert immunologically "cold" tumors into "hot" ones and improve clinical outcomes in CRC.

Wound healing is a complex, highly orchestrated process involving hemostasis, inflammation, proliferation, and remodeling. While acute wounds typically progress through these phases efficiently, chronic wounds-such as diabetic foot ulcers, pressure ulcers, and venous leg ulcers-often stagnate due to persistent bacterial colonization, excessive inflammation, impaired angiogenesis, and reduced extracellular matrix deposition. These pathological features lead to prolonged healing, high recurrence rates, and substantial socioeconomic burdens, which are further exacerbated by global aging, rising diabetes prevalence, and lifestyle-related comorbidities. Conventional wound dressings, including gauze, films, hydrocolloids, and hydrogels, exhibit limitations in infection control, sustained moisture balance, controlled therapeutic release, and adaptability to irregular wound surfaces. Aerogels, a class of ultralightweight, highly porous materials with porosity exceeding 90% and an exceptional surface area, have emerged as promising candidates for advanced wound care. Their unique structure enables superior exudate management, tunable mechanical compliance, and efficient loading of bioactive agents. Composed of inorganic, biopolymeric, or composite matrices, aerogels can be functionalized with antimicrobial nanoparticles, growth factors, or photothermal agents to integrate rapid hemostasis, infection control, immune modulation, and regenerative stimulation within a single platform. However, translational challenges remain, including variability in biodegradation, long-term biocompatibility concerns for certain inorganic systems, high production costs, and scale-up difficulties. This review summarizes recent advances in aerogel-based wound dressings, functionalization strategies, and preclinical evidence while critically analyzing barriers to clinical translation. By bridging multidisciplinary insights, we aim to guide the development of multifunctional aerogel dressings toward precision, intelligent wound care solutions.

[This corrects the article DOI: 10.34133/bmr.0077.].

Adoptive cell-based therapy has emerged as an innovative method for cancer treatment, capitalizing on the innate cytotoxicity of immune cells to eliminate tumors. Although chimeric-antigen-receptor-modified T and natural killer (NK) cells have demonstrated significant therapeutic potential, their clinical translation is hindered by the complex nature of genetic engineering, high production costs, and risks of severe immune-related adverse effects. Addressing these barriers, we present a biomaterial-based approach to engineering NK cells, entirely bypassing the need for genetic modification. Initially, we systematically evaluated the surface modification of NK cells by employing a range of dibenzocyclooctyne (DBCO)-lipid biomaterials based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) lipid: (a) 2 linear structures with different polyethylene glycol (PEG) chain lengths (DSPE-PEG2k-DBCO and DSPE-PEG5k-DBCO), (b) a tadpole structure (DSPE-PEG2k-Di-PEG2k-DBCO), and (c) a branched structure (DSPE-PEG2k-HA-DBCO). The tadpole-shaped DSPE-PEG2k-Di-PEG2k-DBCO exhibited remarkable membrane anchoring, biocompatibility, and preservation of membrane integrity and facilitated the subsequent conjugation of gemcitabine-loaded liposomes (GLipo) through DBCO-azide click chemistry, as validated using fluorescence microscopy. The fabricated GLipo-NK cell-drug conjugates maintained native NK cell viability (>80%) and enabled targeted drug release at tumor sites. Our GLipo-modified NK cells showed superior in vitro cytotoxicity against MIA PaCa-2 pancreatic cancer cells, attributed to a synergistic interaction between immune synapse formation and innate NK-cell-mediated cytotoxicity. This strategy establishes a robust framework for the development of safe, scalable, and effective cell-based immunotherapies aimed at treating solid tumors.

Periodontitis, a highly prevalent chronic inflammatory disease globally, faces substantial challenges in achieving periodontal tissue regeneration, necessitating the development of novel therapeutic strategies. Chinese herbal medicine-derived extracellular vesicles (CHMEVs), natural nanoscale carriers enriched with bioactive components from medicinal plants, exhibit unique therapeutic advantages in tissue repair. Here, we isolated extracellular vesicle-like particles from Paris polyphylla var. yunnanensis leaves (PP-L-EVLPs), a traditional Chinese medicinal herb native to Yunnan, and systematically evaluated their therapeutic potential for periodontal regeneration. PP-L-EVLPs were efficiently internalized by periodontal ligament stem cells (PDLSCs), enhancing their proliferation, migration, and osteogenic differentiation through up-regulation of ALP, RUNX2, and OPN. PP-L-EVLPs significantly suppressed the protein expression levels of lipopolysaccharide-induced interleukin-6 (IL-6) and IL-8 in PDLSCs. In a rat alveolar bone defect model, PP-L-EVLPs significantly promoted bone regeneration, as evidenced by micro-computed tomography, histology, and immunohistochemistry. Biosafety evaluations revealed no histopathological abnormalities or genotoxicity in major organs of Sprague-Dawley rats treated with PP-L-EVLPs. This study is the first to confirm that PP-L-EVLPs exhibit cell migration-promoting, anti-inflammatory, and osteogenic activities with excellent biosafety, offering a novel natural nano-based therapeutic strategy for periodontitis treatment.

Cancer immunotherapy has emerged as a transformative strategy for treating malignancies by harnessing the body's immune system. However, its clinical efficacy is often limited by the complex and immunosuppressive nature of the tumor microenvironment (TME), which poses substantial barriers to therapeutic success. The TME comprises a variety of components, including immune cells, cancer-associated fibroblasts, abnormal vasculature, extracellular matrix, and soluble mediators that collectively support tumor progression, suppress immune surveillance, and contribute to treatment resistance and poor prognosis. Recent advances in nanotechnology have introduced engineered nanomaterials as promising tools to modulate the TME and enhance the outcomes of cancer immunotherapy. These nanomaterials can be precisely engineered to interact with specific elements of the TME, enabling localized delivery, reduced systemic toxicity, and improved therapeutic efficacy. This review provides a comprehensive overview of the role of engineered nanoparticles in targeting both cellular and noncellular components of the TME. It highlights the capacity of nanocarriers to reprogram tumor-associated immune cells, including T cells, dendritic cells, natural killer cells, and tumor-associated macrophages, as well as their ability to target cancer-associated fibroblasts, remodel tumor vasculature, degrade the extracellular matrix, and modulate immunosuppressive mediators. By exploring these multifaceted interactions, we illuminate how rationally designed nanomaterials can reshape the tumor landscape to restore immune function and enhance immunotherapeutic efficacy. Finally, the review addresses current challenges, safety considerations, and future directions necessary to translate these innovations into clinically viable therapies.

Multidrug-resistant (MDR) pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) pose a substantial challenge to global public health, particularly because of chronic and persistent infections associated with bacterial biofilms, which call for safe and innovative therapeutic strategies. Here, we present a novel antibiofilm system inspired by the preferential uptake properties of isogenous bacterial membrane vesicles (MVs). This system employs vancomycin (VAN) for bacterial killing, while MVs act as delivery vehicles to increase VAN penetration into biofilms. VAN@^ΔagrMVs demonstrated sustained drug release and improved VAN accessibility within biofilms. Treatment with VAN@^ΔagrMVs considerably reduced the number of planktonic MRSA strain USA300 cells and effectively eradicated MRSA biofilms in vitro. RNA sequencing revealed substantial alterations in genes associated with bacterial cell wall biosynthesis, global regulators, virulence factors, and biofilm formation. Treatment with VAN@^ΔagrMVs substantially reduced the MRSA burden within biofilms in vivo. Safety evaluation demonstrated the avirulent properties of the VAN@^ΔagrMVs, highlighting its potential for clinical application. Overall, this study offers a promising alternative for MRSA biofilm eradication, providing a viable strategy to combat chronic infections caused by MDR biofilm-forming pathogens.

Soft-tissue sarcoma (STS) is a rare and heterogeneous group of cancers with more than 100 histological subtypes, which makes biological understanding and therapeutic development particularly challenging. Patient-derived tumor organoid models have transformed cancer research by providing patient-representative preclinical platforms, yet their application in STS has been limited because of low establishment efficiency. To address this problem, a gelatin-based culture protocol was developed to enhance critical cellular processes, including mitochondrial function and cell adhesion, which are essential for organoid self-organization. Using this optimized system, patient-derived tumor organoids were successfully established from representative STS subtypes, such as dedifferentiated liposarcoma and leiomyosarcoma. These organoids retained the histopathological architecture and molecular characteristics of the original tumors and reflected subtype-specific oncogenic pathways, mitochondrial dynamics, and lipid metabolic signatures. Our established gelatin-based organoid culture system enables efficient establishment of patient-derived organoids from representative STS subtypes, faithfully preserving their histopathological and molecular characteristics. These models recapitulate subtype-specific oncogenic pathways, mitochondrial dynamics, and lipid metabolic signatures, providing a robust and clinically relevant preclinical platform for investigating sarcoma biology and developing personalized therapeutic strategies.

NIR-II small-molecule-based bimodal imaging systems accurately unify diagnosis and therapeutics for precision tumor therapy, which is attributed to their easily modifiable structures, high potential biocompatibility. In particular, the highly efficient photodiagnostic agent with high light-to-heat transformation performance and fluorescence/photoacoustic imaging (FLI/PAI) with the range of near-infrared-II (NIR-II; 900 to 1,700 nm) has emerged as a popular research topic. This study reported a series of Aza-boron-dipyrromethenes (Aza-BODIPY) dyes (Aza-A/B/C) with donor-acceptor structure through the introduction of diethylaminobenzene (electron donor) and (iso)quinoline (electron acceptor) into the Aza-BODIPY backbone. Compared to Aza-A/B, the enhanced light trapping ability, the decreased NIR-II fluorescence emission performance, and poor reactive oxygen species generation capacity made Aza-C as an optimal photothermal agent. Through 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-mPEG₂₀₀₀) capping, the as-prepared Aza-C nanoparticles (Aza-C NPs) showed excellent biocompatibility, super stability, outstanding light-to-heat transformation performance (ƞ = 58.2%), as well as concentration-dependent linear FL/PA signals, which guaranteed that Aza-C NPs could be successfully utilized for NIR-II FLI/PAI-directed efficient photothermal therapy (PTT) of cervical tumor, with high tumor inhibition rates of over 90%. Introducing diethylaminobenzene and (iso)quinoline to Aza-BODIPY backbone help to construct NIR-II Aza-C dye for NIR-II FLI/PAI-directed efficient tumor PTT. This novel approach offers a promising avenue toward the ablation of tumors in deep tissues.