ACS Biomaterials Science & Engineering最新文献

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.

Mechanoresponsive biomaterials are a revolutionary class of materials designed to respond dynamically to mechanical stimuli, providing tissue engineering and regenerative medicine with precise control over biological processes. Through processes including supramolecular interactions, strain stiffening, and force-induced conformational changes, these materials, which include hydrogels, elastomers, and piezoelectric composites, imitate the mechanics exclusive to biological tissues. Additionally, mechanoresponsive systems improve drug delivery by releasing drugs in response to pH changes or mechanical strain using various materials, including magnetic scaffolds and ultrasound-triggered micelles. Despite advancements in numerous arenas of biological sciences, problems with clinical translation, scalability, and long-term biocompatibility still exist. New developments combine technologies like 4D bioprinting to create dynamic, patient-specific scaffolds and artificial intelligence (AI)-assisted design to maximize material qualities. To achieve material innovation with the desired level of biological complexity, future initiatives should focus on multifunctional platforms that combine mechanical, electrical, and biochemical inputs at an advanced level. This review dives into several aspects of mechanoresponsive biomaterials by navigating through the fabrication methods, underlying principles, inception of these in biomedical applications, and progression through the current research settings.

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.

Microvascular networks (MVNs) formed via endothelial cell self-assembly in 3D hydrogels have emerged as a widely used platform for modeling vascularized tissues and studying vascular pathophysiology. Conventional MVN systems incorporate supporting fibroblasts and may include biochemical cues such as VEGF, FGF, or S1P, as well as mechanical stimuli like luminal flow, yet the impact of these variables on MVN morphology and function remains incompletely understood. Here, we systematically investigated the effects of fibroblast concentration, fibroblast-conditioned media, angiogenic factors, and luminal flow on the morphology, perfusability, and vessel wall integrity of MVNs cultured in microfluidic vasculature-on-a-chip. In addition to standard branch-based metrics, such as vessel coverage area and vessel diameter, we developed and applied novel void-based morphological parameters that quantify the size, shape, and spatial distribution of vessel-free spaces. These metrics enabled us to capture subtle morphological differences across MVN culture conditions and to quantify the dynamic morphogenesis events that shaped the resulting MVNs including branch formation, vessel fusion, and pruning. Our results demonstrate that high fibroblast-to-endothelial cell ratios accelerate MVN formation but promote excessive vessel fusion, while MVNs cultured without fibroblasts─using only conditioned media or soluble factors─exhibited patch-like, nonphysiological morphology with reduced branch formation. Direct inclusion of fibroblasts proved to be essential for promoting the thin, interconnected vascular structures characteristic of in vivo microvasculature and could not be substituted by soluble cues alone. Overall, our void-based analysis method enabled more sensitive discrimination of MVN morphological features than traditional branch-based metrics and offers a reduced-data, high-content approach suitable for potential integration with machine learning and AI-assisted image analysis pipelines. This platform provides a new framework for optimizing MVN culture protocols and advancing vascular tissue engineering studies, particularly for the advancement of organ-on-a-chip (OOC) and microphysiological systems.

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.

We describe the osteogenic potential and hemocompatibility of rare-earth-doped hydroxyapatite in a murine preosteoblastic (MC3T3-E1) cell line, aiming to assess the osteoblast differentiation effect of ytterbium-, terbium-, cerium-, and europium-doped hydroxyapatite through alkaline phosphatase activity and the expression levels of osteogenic marker genes, including Runx2, ALP, OPN, and BMP2. Our findings reveal various levels of enhancement in early osteogenic activity across the four dopants. Among the dopants tested, europium- and ytterbium-doped hydroxyapatites produce the most pronounced effects, significantly enhancing ALP activity and upregulating multiple osteogenic genes. Cathodoluminescence spectroscopy confirms successful incorporation of all rare-earth ions in the HAp lattice, while hemocompatibility and cell viability assays demonstrate that all compositions are biocompatible and safe for contact with blood, providing a comparative framework for understanding how rare-earth dopants influence early osteogenic response. These findings demonstrate the potential of Eu- and Yb-doped hydroxyapatites as bioactive materials for bone regeneration.

Background: Polyetheretherketone (PEEK) is a promising alternative to titanium alloy for dental implants due to its bone-mimicking elastic modulus, which mitigates stress shielding. However, its bioinert nature limits osseointegration. Methods: We developed a novel PEEK variant, PEEK-chondroitin sulfate zinc (PEEK-CSZn), by chemically grafting zinc and chondroitin sulfate onto the PEEK surface. Material properties were characterized using SEM, FTIR, EDS, and ICP-MS. Anti-inflammatory, osteogenic, and angiogenic effects were evaluated in vitro using MC3T3-E1, HUVEC, and RAW264.7 cells and in vivo using a rabbit femur bone defect model. Results: Characterization confirmed successful CSZn integration. In vitro, PEEK-CSZn at 500 μg/mL enhanced the MC3T3-E1 cell proliferation. Osteogenic markers (OCN and Osterix) were upregulated by around 2.3- and 1.8-fold, respectively, in MC3T3-E1 cells (p < 0.05). Inflammatory markers (IL-6 and IL-12a) in RAW264.7 cells decreased by 23% and 49%, respectively (p < 0.05), while angiogenic markers (VEGF and CD31) in HUVECs increased by 2.2- and 2.8-fold (p < 0.05). In vivo, Micro-CT analysis revealed PEEK-CSZn increased bone volume fraction (BV/TV) and BMD compared to unmodified PEEK at 8 weeks postimplantation (p < 0.05). Conclusions: PEEK-CSZn exhibits trifunctional bioactivities, including anti-inflammatory, osteogenic, and angiogenic, and thus significantly enhances osseointegration, making it a promising material for advanced dental implant applications.