ACS Biomaterials Science & Engineering最新文献

Traditional Chinese medicine (TCM) compound formulas are widely employed in the clinical management of osteoporosis; however, their principal bioactive constituents and primary molecular targets remain poorly characterized. Consequently, there is an urgent need for systematic functional exploration of TCM-derived chemicals. In this study, we applied a network pharmacology-based approach to screen four canonical TCM compound prescriptions for antiosteoporotic compounds, identifying a total of 20 candidate molecules. Among these, quercetin was selected as a lead compound for the synthesis of biologically active carbon dots (CDs), which were then integrated with mesoporous silica nanoparticles (MSNs) to construct a reactive oxygen species (ROS)-responsive nanocarrier system. In vitro cellular assays demonstrated that both the quercetin-derived CDs and the drug-loaded nanocarriers exhibited excellent cytocompatibility, robust osteogenic-promoting activity, and potent osteoclast-inhibitory effects. Collectively, our findings underscore the utility of network pharmacology in identifying quercetin as a promising TCM-derived lead compound for osteoporosis intervention, and the rational functionalization strategy developed herein provides a valuable paradigm for advancing the therapeutic application of TCM-derived chemicals in bone metabolic disorders.

Bovine milk-derived exosomes (mExos) are scalable, biocompatible nanocarriers well-suited for the cross-barrier transport and protection of labile nucleic acid therapeutics. However, achieving precise active targeting for cargo delivery remains challenging, as conventional surface functionalization methods often lack site-specificity, unintentionally altering native physicochemical properties or obscuring essential membrane interactions. Herein, we report a modular glycoengineering strategy that leverages the dense sialic acid coating on mExos to introduce versatile anchoring sites for targeting ligand modification via sequential chemoenzymatic remodeling. Specifically, the native terminal sialic acids on the mExo surface were enzymatically removed and replaced with azide-modified sialic acid analogs, which was achieved efficiently through an integrated multienzyme reaction. In principle, the resulting platform, mExo-N3, enables the glycan-selective conjugation of any dibenzocyclooctyne (DBCO)-modified targeting ligands for targeted delivery, avoiding the limitations of random modifications. To validate this platform, we conjugated mExo-N3 with an anti-EGFR nanobody (7D12) and encapsulated a microRNA-21 inhibitor (miR-21i). The resulting mExo-7D12@miR-21i construct maintained colloidal stability and exhibited specific internalization by EGFR-positive cancer cells. Intracellular delivery of miR-21i restored the expression of tumor suppressors PTEN and PDCD4, inducing apoptosis and suppressing proliferation. Furthermore, in an A431 xenograft model, the targeted system achieved 58.3% tumor growth inhibition in vivo without evident systemic toxicity. By converting native glycans into functional anchoring sites, this approach provides a translatable framework for customizing exosomal delivery vectors into targeted therapeutics.

Photodynamic therapy (PDT) is a promising approach for cancer treatment. However, PDT has been limited by oxygen (O2) availability in tumor tissues, particularly within hypoxic regions. A PEGylated nitrogen-doped carbon nanohorn (NCNH) has unique structural properties that encapsulate O2 and deliver it efficiently to tumor sites, overcoming the limitation of O2 availability. The O2 uptake on O2-loaded PEGylated NCNH nanocarriers was approximately 1.24 times higher than O2-loaded pristine NCNH and 0.80 times that of O2-loaded nanocarriers with additional O2 adsorbers of dendrimers (DEN) and fluorocarbons (F) named NCNH/DEN-F/F-PEG. Then, singlet oxygen was generated nearly proportionately to the O2 loading. However, on cellular uptake, PEGylated NCNH and NCNH/DEN-F/F-PEG had higher uptake (81.7% and 90.4%, respectively) than pristine NCNH (51.2%), implying the superior uptake ability of PEGylated carriers. From high singlet oxygen generation and the preferable cellular uptake, the decrease in cell viability of MCF-7 breast cancer cells, which were incubated with O2-loaded nanocarriers under light irradiation, occurred at the lowest concentration (IC50 = 9.6 µg/mL) for NCNH/DEN-F/F-PEG. This innovative strategy not only advances much production of singlet oxygen by accumulating O2 adsorber units but also facilitates the uptake of carriers into biological membranes by PEGylating, enhancing the therapeutic outcome and contributing to personalized and effective cancer therapies.

Oral submucous fibrosis (OSF) is a chronic, progressive, and potentially malignant disorder characterized by severe oral cavity remodeling. The condition is driven by a painful burning sensation and a pathognomonic restriction of mouth opening (trismus), severely diminishing patients' quality of life. Current clinical management represents a critical bottleneck in patient care, as conventional strategies rely heavily on painful intralesional injections or systemic regimens plagued by localized toxicity and poor compliance. Consequently, there is an urgent demand for localized, noninvasive, and patient-compliant delivery systems capable of sustaining therapeutic drug levels directly at the fibrotic site. To address this challenge, we developed, optimized, and characterized a multilayered buccal film ("sandwich" architecture) combining bupivacaine (Bupi) and pirfenidone (PFD) to achieve an immediate anesthetic effect followed by sustained antifibrotic action. A Design of Experiments (DoE) approach optimized both formulation composition and the critical process parameter (drying rate), yielding a fast-dissolving (FD) layer engineered for rapid Bupi release alongside a slow-dissolving (SD) layer tailored for prolonged PFD dissolution. The resulting monolithic system successfully immobilizes both therapeutics in a stable amorphous state, leveraging macromolecular free volume and modulated surface microtopography to regulate biphasic release kinetics. This work demonstrates the feasibility of engineering kinetically distinct, multilayered buccal films through rational design, providing a translationally viable therapeutic platform for localized management of oral fibrosis.

Skin wound healing involves four overlapping phases, with angiogenesis and mitochondrial functional recovery being critical for effective repair. In this study, a platelet-derived growth factor (PDGF)-mimetic peptide hydrogel was constructed and combined with bioactive glass to form a PDGF-mimetic peptide@BG composite system, aiming to synergistically promote wound healing. The structural stability and morphology of the PDGF-mimetic peptide@BG were characterized using electron microscopy and spectroscopic techniques. Biocompatibility was assessed through in vitro cell experiments. A full-thickness skin defect model in mice was established, and wound healing, angiogenesis, and mitochondrial functional recovery were evaluated using histological staining, Western blotting, and immunofluorescence. The involvement of the RhoA/Rock1/Drp1 signaling pathway in mitochondrial function improvement was investigated. The PDGF-mimetic peptide@BG was successfully prepared with stable structure. In vitro experiments demonstrated good biocompatibility and promotion of endothelial cell proliferation and migration. In vivo results confirmed that PDGF-mimetic peptide@BG accelerated wound healing in mice, enhanced granulation tissue formation and collagen deposition, and increased local blood flow and angiogenesis. Furthermore, the composite restored mitochondrial function, as evidenced by reduced ROS levels, elevated ATP and SOD activity, improved mitochondrial morphology, and downregulation of mitochondrial fission-related proteins. Mechanistic studies suggested that PDGF-mimetic peptide@BG may exert its reparative effects at least in part through inhibition of the RhoA/Rock1/Drp1 signaling pathway. This study suggests that the PDGF-mimetic peptide@BG significantly promotes tissue regeneration in a normal murine wound model by increasing wound blood flow, enhancing vascularization, accelerating mitochondrial repair, and improving its structure and function. These findings provide a preliminary foundation for further evaluation in clinically relevant impaired-healing models.

Extracellular vesicles (EVs) are emerging as critical players in oncology and also exert vital regulatory effects on exercise-induced muscle injury repair, offering novel insights into tumor biology. Tumor-derived EVs facilitate intercellular communication by carrying bioactive molecules such as proteins and nucleic acids, which reshape the tumor microenvironment and enhance tumor invasion, metastasis, and drug resistance. Conversely, specific subsets of EVs, particularly those derived from dendritic cells or engineered to present tumor antigens, can elicit antitumor immune responses by activating cytotoxic T lymphocytes and facilitating antigen cross-presentation. Clinically, the high stability of EVs in body fluids, coupled with their intrinsic capacity to encapsulate and protect tumor-derived molecular cargo, positions them as robust noninvasive biomarkers for early cancer diagnosis and prognostic stratification, as well as indicators for evaluating muscle recovery status after exercise. Additionally, EVs function as drug delivery carriers, offering advantages like biocompatibility, low immunogenicity, and targeting capabilities. However, challenges remain in EVs isolation, characterization, and scalable production, with inconsistent techniques affecting purity, structure, and biological activity. Moreover, limited understanding of EVs mechanisms, such as their role in immune modulation and drug delivery efficiency, hinders broader clinical translation across oncology and musculoskeletal rehabilitation. Addressing these issues requires advances in standardization, scalable manufacturing, and extensive clinical trials to ensure its safety and efficacy. Despite these challenges, EVs hold immense promise as transformative tools in precision oncology and sports rehabilitation, paving the way for innovative diagnostics, therapies, and improving patient and athletic outcomes in the fight against cancer and exercise-related muscle damage.

Cell-free DNA (cfDNA) has emerged as an important mediator of autoimmune inflammation and a promising therapeutic target for restoring immune homeostasis. Excessive cfDNA activates nucleic acid-sensing pathways such as Toll-like receptor 9 (TLR9) and stimulator of interferon genes (STING), which drive proinflammatory responses and worsen tissue injury. Researchers have developed various biomaterial-based cfDNA scavengers to neutralize or eliminate pathogenic cfDNA. This review summarizes recent advances in the design, functional mechanisms, and therapeutic potential of cfDNA-clearing materials for autoimmune diseases. Representative systems-including cationic polymers, enzyme-based platforms, and metal-organic framework-are discussed in terms of their structural features, cfDNA-binding, and immunomodulatory effects. Particular attention is given to how these materials suppress cfDNA-triggered inflammatory signaling and alleviate disease manifestations in rheumatoid arthritis and other autoimmune disease models. Finally, we discuss challenges for clinical translation, including biosafety, target specificity, in vivo stability, and the lack of evaluation standards. Overall, cfDNA-scavenging biomaterials offer a promising platform for modulating aberrant inflammation in autoimmune diseases.

Smooth muscle cells (SMCs) are a critical cellular component of the tunica media of blood vessels in arteries and arterioles. Despite their importance, the development of in vitro arteriole models with diameters <200 µm remains challenging, largely due to difficulties in culturing SMCs at these length scales. In particular, uncontrolled SMC overproliferation can lead to microvessel vessel narrowing and occlusion. Here, we report a 3D microfluidic-based tissue-engineered model with human brain SMCs forming a microvessel approximately 150 μm in diameter within a collagen I hydrogel. Using this platform, we demonstrate that serum-free culture conditions are essential to prevent SMC overproliferation and maintain vessel patency. In addition, SMCs cultured in serum-free and serum-supplemented conditions exhibit distinct functional phenotypes, consistent with previous studies in 2D culture. These results provide a strategy for fabrication of tissue-engineered arteriole models.