ACS Biomaterials Science & Engineering最新文献

The mechanical properties of the extracellular matrix play a key role in regulating cellular functions, yet many in vitro models lack the mechanical complexity of native tissues. Traditional hydrogel-based substrates offer tunable stiffness but are often limited by instability, porosity, and coupled changes in both mechanical and structural properties, making it difficult to isolate the effects of stiffness alone. Here, we introduce a spatially patterned dual-cure polydimethylsiloxane (DC-PDMS) system, a nonporous, mechanically tunable polymer that allows for precise spatial control of stiffness over a range of patho-physiological values. This platform enables the design and creation of in vitro models for studying the influence of spatial mechanical cues on cellular behavior. To demonstrate its utility, we examined primary cardiac fibroblast responses across different substrate stiffness conditions. Fibroblasts on soft regions exhibited rounded morphologies with disorganized actin networks, while those on stiffer regions became more elongated with highly aligned stress fibers, indicating stiffness-dependent cytoskeletal remodeling. Stiff substrates also led to nuclear compression and increased nucleus curvature, correlating with increased nuclear localization of YAP, a key mechanotransduction regulator. By allowing cells to interact with mechanically distinct regions within a single substrate, this system provides a powerful approach for investigating mechanotransduction processes relevant to fibrosis and other mechanically regulated diseases. The ability to create stiffness patterns with subcellular resolution makes DC-PDMS a valuable tool for studying cell-material interactions, enabling new insights into mechanobiology-driven cellular responses and therapeutic targets.

Effective bone regeneration requires not only robust osteoinduction but also precise immunomodulation to orchestrate the complex healing process. In this study, we present a strategy for engineering multifunctional three-dimensional (3D) stem cell spheroids (Sphe-BP-IL4-BMP2) by integrating black phosphorus (BP) nanosheets coloaded with interleukin-4 (IL-4) together with recombinant human bone morphogenetic protein-2 (rhBMP-2). BP nanosheets served as a biodegradable scaffold and a delivery vehicle, enabling sustained release of rhBMP-2 and IL-4 to enhance osteogenic differentiation and to promote anti-inflammatory M2 macrophage polarization, respectively. The resulting spheroids exhibited a well-defined morphology, enhanced cell viability, and uniform BP nanosheet distribution. The in vitro studies demonstrated Sphe-BP-IL4-BMP2 has significantly upregulated osteogenic markers and ALP activity alongside potent immunomodulatory effects on macrophages. Further in vivo implantation into a rat calvarial defect model led to increased angiogenesis and accelerated bone regeneration without adverse effects. The results highlight the therapeutic synergy between osteoinductive and immunomodulatory cues within a 3D spheroid platform, offering a promising avenue for treating critical-sized bone defects.

Choroidal neovascularization (CNV) represents a major cause of vision loss in various retinal diseases such as age-related macular degeneration (AMD). Current treatment involves frequent, often monthly, eye injections. The development of minimally invasive, long-term, painless, and effective ocular drug delivery systems is crucial for advancing the treatment of AMD. This study explores a novel method that integrates controllably bioresorbable silicon nanoneedles loaded with bevacizumab (Si NNs-Bev) on a tear-soluble subconjunctival patch for sustained, 1 year ocular drug delivery. The Si NNs-Bev embed into the sclera in a minimally invasive manner, undergoing controlled degradation over one year. This approach facilitates the sustained release of therapeutic agents, enhancing treatment efficacy and reducing treatment burden. Si NNs-Bev for the treatment of CNV are validated in a rabbit model of AMD. The SiNN-Bev patch achieved a sustained therapeutic effect on CNV regression, with a mean reduction of 82% by 4 months that is persistent for at least 1 year with minimal recurrence, which is consistent with the localized drug delivery mechanism facilitated by the transscleral microneedles. These preliminary findings underscore the potential of SiNNs as a platform technology for long-term, sustained ocular therapeutics.

Bone regeneration is generally not effective in cases of extensive defects or inflammatory conditions such as osteoporosis and periodontitis. The traditional approach, such as bone grafting, comes with limitations, thereby making tissue engineering strategies a potential alternative. However, successful regeneration needs both osteogenesis and proper immunomodulation. Among all the immune cells, macrophages play a pivotal role in osteoimmunomodulation because of their plasticity in switching between pro-inflammatory (M1) and anti-inflammatory (M2) states. Nanostructured biomaterials can change the polarization of macrophages by altering important immune pathways such as NF-κB, MAPK, PI3K-Akt, JAK-STAT, NLRP3, Notch, and HIF-1 due to their large surface area and adjustable surface chemistry. These nanomaterials have also demonstrated excellent efficacy as carriers for targeted delivery of osteoimmunomodulatory bioactive agents, such as growth factors, cytokines, metal ions, and phytochemicals. In this review, we have discussed the crosstalk between the skeletal system, nanomaterials, and the immune system. We have also discussed the various types of nanomaterials and the design strategy of nanomaterials to modulate immune responses for enhanced bone regeneration. A brief discussion about the molecular pathways involved in osteoimmunomodulation and the modulation of these pathways by nanostructured materials for bone repair is also provided. Finally, we examined how nanomaterials can be engineered as delivery platforms for the controlled release of bioactive molecules involved in immune modulation and bone regeneration.

This study presents the development of titanium-based implants coated with zeolite layers for controlled delivery of epigallocatechin gallate (EGCG), a polyphenolic compound with osteogenic, antiresorptive, and antibacterial properties. Zeolite coatings were modified with divalent ions (Zn²⁺, Mg²⁺, Ca²⁺) to investigate their influence on EGCG adsorption and release under neutral (pH 7.4, SBF) and acidic (pH 5.0, acetate buffer) conditions. Comprehensive characterization using SEM, EDS, FT-IR, UV-vis spectroscopy, and surface profilometry confirmed uniform zeolite formation, effective EGCG loading, and tunable release profiles. Zinc-containing zeolite exhibited the highest EGCG adsorption but demonstrated cytotoxicity toward hFOB 1.19 osteoblasts. Magnesium-zeolite-coated implants provided controlled EGCG release, were nontoxic, and did not support cell adhesion, making them suitable for temporary internal fixation in the management of orthopedic trauma. Release studies revealed pH-dependent kinetics, with accelerated EGCG release under acidic conditions simulating osteoclast activity. These findings demonstrate the potential of Mg-zeolite-coated titanium implants as functional devices that provide mechanical support, enable localized drug delivery, and promote bone regeneration while minimizing tissue damage during removal.

A novel core-shell hybrid material composed of bioactive glass (BG) nanoparticles and the metal-organic framework (MOF) MIL-100(Fe) (Fe₃O(H₂O)₂OH(BTC)₂·nH₂O, BTC: 1,3,5-benzenetricarboxylate) was synthesized using a layer-by-layer strategy. The formation of the MIL-100(Fe) shell on the BG core was directly confirmed by high-resolution transmission electron microscopy, which revealed a continuous MOF layer with an average thickness of 6.1 ± 0.9 nm. Complementary characterization by infrared spectroscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, N₂ sorption, and synchrotron-based X-ray absorption spectroscopy (XAS) confirmed the coexistence of MIL-100(Fe) and BG components and their structural integrity within the hybrid material. Notably, for the first time, a synchrotron-based technique (XAS) was used to characterize the MOF@BG system, providing unique insight into its local coordination environment and structural evolution. The hybrid material demonstrated favorable cytocompatibility in a long-term (21-day) assay on mouse osteoblast precursor cells (MC3T3) and human dermal fibroblasts (HDF). At the same time, it did not induce ex vivo hemolysis at concentrations up to 1000 μg/mL. The induction of osteogenic differentiation in MC3T3 cells in the presence of MIL-100(Fe)@BG was confirmed by early osteogenic markers, including alkaline phosphatase (ALP) activity and alizarin red staining (ARS). Bioactivity studies in Dulbecco's phosphate-buffered saline (DPBS) and simulated body fluid (SBF) revealed rapid formation of nanohydroxyapatite, beginning within the first hours of incubation. Importantly, under physiological conditions, the MIL-100(Fe) shell undergoes a controlled structural transformation, yielding highly dispersed nanoscale Fe₂O₃ particles. These nanoparticles induce the production of reactive oxygen species (ROS) and contribute to antibacterial activity, thereby inhibiting E. coli and S. aureus without the need for external antimicrobial agents. The combination of bioactivity, osteogenic potential, hemocompatibility, and intrinsic antibacterial functionality positions MIL-100(Fe)@BG as a promising multifunctional platform for bone regeneration and infection control.

The repair of diabetic wounds is constrained by persistent inflammatory responses, excessive reactive oxygen species, and compromised angiogenesis, necessitating novel therapeutic strategies to modulate the immune microenvironment and promote tissue repair. Exosomes isolated from human embryonic kidney 293 cells (293-Exo) possess a high content of bioactive cargo and have been shown to markedly enhance the repair of diabetic wounds. In addition, extracellular vesicles originating from plants are increasingly recognized as a promising new class of therapeutic agents. Tomato fruit juice-derived exosomes (TM-Exo) can significantly reduce oxidative stress, regulate macrophage polarization, and protect islet function, holding significant promise for treating diabetic wounds. Nevertheless, topical administration of exosomes at wound sites is hampered by intrinsic instability and rapid clearance, which markedly constrains their translational and clinical potential. This study developed a multifunctional bioactive dressing (TE/293E-Gel) based on a photo-cross-linked methacrylamide hyaluronic acid/tannic acid (HAMA/TA) hydrogel, coencapsulating 293-Exo and TM-Exo to synergistically promote diabetic wound healing. This hydrogel possesses excellent mechanical properties, tissue adhesion, controllable degradability, and good biocompatibility. This bioactive agent vigorously enhances cell motility and angiogenic processes, repolarizes macrophages from an inflammatory M1 profile toward a reparative M2 program, and concurrently affords antioxidative and anti-inflammatory benefits. In conclusion, the designed photo-cross-linked hydrogel encapsulating exosomes from two distinct sources significantly accelerates diabetic wound repair through multiple mechanisms, demonstrating significant translational potential.

Background: Chemical debridement agents are commonly used during the cleaning of implants for peri-implantitis treatment; however, how these agents affect lesion healing remains unclear. In addition, the dose- and time-dependent effects of these residuals on implant biocompatibility remain poorly understood.

Materials and methods: We evaluated the effects of active compounds in commercial products-3% hydrogen peroxide (H₂O₂), 0.43% sodium hypochlorite (NaClO), and 0.12% chlorhexidine with 0.05% cetylpyridinium chloride (CHX-CPC) at graded dilutions on murine osteoblastic cells (MC3T3-E1), human gingival fibroblasts (HGFs), and human bone marrow mesenchymal stromal cells (hBMSCs). Cells were cultured for 24 h, then exposed to the agents for 2, 12, or 24 h. Cytotoxicity and viability were assessed using lactate dehydrogenase (LDH) release and CCK-8 assays, while cell morphology was examined by scanning electron microscopy (SEM). Apoptotic gene expression (BCL2, MCL1, BAX) was analyzed after 2 h using quantitative PCR.

Results: At high concentrations, H₂O₂ and NaClO significantly reduced LDH activity in supernatant, likely due to oxidant-induced enzyme inactivation. All three agents inhibited cell viability in a dose- and time-dependent manner, accompanied by cell shrinkage and deformation. Among the tested cell types, hBMSCs displayed greater resistance to H₂O₂, maintaining proliferative viability at 0.15% (1:20 dilution). Gene expression analysis revealed that concentrated H₂O₂ and CHX-CPC downregulated BCL2 and MCL1 expression in MC3T3-E1 cells, with broader suppression of these genes observed in HGFs across all agents. In hBMSCs, high concentrations of the agents did not significantly reduce BCL2 and MCL1 levels.

Conclusion: Residual chemical debridement agents, when inadequately removed, compromise the viability of cells in peri-implant tissues in a dose- and time-dependent manner. hBMSCs exhibited greater resistance to apoptosis than MC3T3-E1 cells and HGFs. Thorough removal of residual chemical cleaning agents after peri-implant debridement is therefore crucial to preserve the biocompatibility of the implant and the healing potential of peri-implant tissues.

Magneto-photoresponsive polymeric microspheres represent a promising platform for targeted, externally triggered drug delivery. However, achieving precise control while minimizing phototoxicity remains a major challenge. In this study, we developed biodegradable core-shell microspheres composed of acetalated dextran (AcD) and cellulose modified by citric acid (CMC), co-loaded with a photoacid generator (PAG), Fe₃O₄ nanoparticles, and zerovalent iron (ZVI). These components enable dual-stimuli responsiveness, in which short UV exposure (365 nm, 10 min on/off cycles) and an alternating magnetic field (AMF, 150 Oe) act synergistically to enhance photoacid generation and trigger rapid drug release. Upon dual stimulation, the system exhibited rapid release kinetics, with cumulative release reaching ∼98% for curcumin within 45 min and ∼98% for doxorubicin (DOX) within 60 min. Cytocompatibility studies showed minimal toxicity toward healthy HEK293 cells, while DOX-loaded microspheres reduced viability of HepG2 liver cancer cells to ∼14% after 24 h. In 3D MCF-7 spheroid models, DOX-loaded microspheres induced significant spheroidal disintegration and a ∼41% reduction in acid phosphatase activity over 21 days. This work demonstrates a programmable, biodegradable, magneto-photoresponsive microsphere system capable of efficient and tumor-selective drug delivery, offering great potential for next-generation localized chemotherapy applications.

Mussels, an ecologically diverse group of bivalve molluscs, have attracted attention due to phenomenal adaptability across marine and estuarine environments and an exceptional ability to adhere strongly to wet and dynamic substrata by secreting specialized adhesive structures called byssal threads. These proteinaceous structures, which are secured by sticky plaques, enable mussels to sustain harsh environments and powerful currents. The cuticular covering of byssal thread is mechanically strong but flexible, with reversible metal-ligand coordination, particularly Fe³⁺-DOPA bonds that provide load-dissipating and self-healing properties. The unique combination of different properties, including mechanical, metal-binding, and self-healing, has been attributed to unique proteins synthesized by mussels called mussel foot proteins (mfps) found within the byssus, which is rich in catechol-containing residues such as DOPA. Numerous environmental factors affect the development and functional efficacy of byssus. Motivated by the remarkable properties of mussels, scientists have developed a wide range of bioinspired materials. This review presents an overview of different mussel species as well as structural and functional characteristics of the byssal threads. Besides focusing on their mechanical strength and biocompatibility, this study examines recent advancements in mussel-inspired hydrogels and scaffolds for bone regeneration, motion detection, and wound healing. Further emphasizing unique adhesion chemistry, this review highlights the development of next-generation biomaterials and healthcare technologies, especially smart biosensors and multifunctional theranostic platforms for integrated disease diagnostics and targeted therapy.