ACS Biomaterials Science & Engineering最新文献

To investigate the ability of novel Gyroid-shaped titanium alloy (TC4) porous bioscaffolds to induce angiogenesis and osteogenesis in bone defect areas. This study employed selective laser melting (SLM) technology to fabricate Gyroid shaped and Cube-shaped TC4 porous bioscaffolds, using the commonly used cube shape as a control. The unit cell size was 4 mm, with a wall thickness or rod diameter of 300 μm and a porosity of approximately 80%. These scaffolds were implanted into rabbit mandibular defect sites (10 mm × 7 mm × 5 mm) to evaluate the angiogenic and osteogenic potential of the Gyroid-shaped scaffold. Material characterization revealed that sandblasted and acid-etched (SLA) TC4 scaffolds met design specifications, exhibiting uniformly distributed micrometer-scale pores and enhanced surface hydrophilicity. Histological staining revealed that compared to the Cube-shaped scaffold, the Gyroid-shaped scaffold induced greater angiogenesis and new bone formation within the bone defect area. Both scaffolds demonstrated good biocompatibility. Western Blot and RT-qPCR results indicated that the Gyroid-shaped scaffold possessed superior angiogenesis potential (compared to the Cube-shaped scaffold). During the early implantation phase (1–2 weeks), Gyroid-shaped scaffolds exhibited higher expression of platelet-endothelial cell surface adhesion molecule 1 (CD31) and endothelial mucin (EMCN). Concurrently, vessel distribution within the scaffold showed spatial variation. Additionally, gene expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) was elevated in the early bone defect area. Imaging analysis confirmed successful implantation of both scaffolds, with the Gyroid-shaped scaffold exhibiting a higher proportion of new bone formation. Consequently, the novel Gyroid-shaped TC4 porous bioscaffold demonstrates excellent potential for angiogenesis and osteogenesis, providing a reference for Gyroid-shaped scaffold-based bone defect repair.

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.

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.

Bacterial infection remains a major challenge in biomedical applications, particularly with the rise of antibiotic-resistant pathogens. Developing antibacterial biomaterials that both prevent infection and support tissue regeneration has become an essential goal in biomedical research. Silk fibroin (SF) is a natural protein derived from Bombyx mori which has been identified as a broad-spectrum, biocompatible, and programmable material in biomedical applications. This review emphasizes SF for antibacterial infection, summarizing its structural features and modulations to immune responses and synergistic combination with multiple antibacterial agents. The unique β-sheet structure of silk fibroin provides resilience and tunable functionality, allowing it to serve as a stable matrix for diverse antibacterial agents. Antibacterial agents enhance antibacterial performance by generating reactive oxygen species, disrupting bacterial membranes, and suppressing biofilm formation. Silk fibroin supports immune modulation by promoting macrophage polarization and reducing inflammation, thereby facilitating tissue repair and wound healing. Overall, SF represents a next-generation antibacterial biomaterial that integrates antimicrobial efficacy with immune modulation, structural tunability, and biocompatibility, having strong potential for infection control and tissue regeneration in clinical applications. Despite advancements in biofunctionality, optimization of controlled release and long-term compatibility challenges still exist for SF’s clinical applications, particularly against antibiotic-resistant pathogens.

Spinal cord injury (SCI) leads to irreversible sensory and motor deficits due to its limited capacity for regeneration of the central nervous system (CNS). While the current clinical strategies focus on neuroprotection and stabilization of the symptoms, they offer very little in terms of restoring long-term functional recovery. Three-dimensional (3D) bioprinting has opened new possibilities for constructing patient specific scaffolds that mimic the structural and biochemical complexities of native spinal tissue. The incorporation of cells, biomaterials, and growth factors, in 3D bioprinting provides incomparable control over the architecture of the scaffold, which in turn enables recreation of biomimetic environment that supports axonal outgrowth and neural recovery following SCI. This review focuses on the recent advances in 3D bioprinting techniques for SCI repair and discusses the potential of the techniques to be implemented in SCI models. Focus is placed on the bioink formulation, scaffold design strategies, and emerging functional features. The amalgamation of current findings underscores the potential of 3D bioprinting as a mature platform for the development of next-generation therapies for spinal cord injury.

This study aimed to reconstruct the hypothalamic–pituitary axis using an organ-on-a-chip (OOC) model and to evaluate the modulatory role of phoenixin-20 (PNX) in the regulation of the gonadotrophic axis in sheep. Sixteen female Polish Merino lambs were used as tissue donors to create microfluidic chips containing paired hypothalamic and pituitary slices connected via perfused channels. This system enabled continuous medium flow and maintenance of functional neuroendocrine interactions under ex vivo conditions. The OOC platform was used to analyze changes in the expression of gonadotropin-releasing hormone (GnRH), kisspeptin (Kiss), neurokinin B (NKB), and prodynorphin (pDYN) in the hypothalamus, as well as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) expression and secretion in the pituitary. PNX treatment significantly increased hypothalamic GnRH expression, while the blockade of neuropeptide Y receptors (NPY1R and NPY5R) diminished this response, suggesting that PNX effects are at least partially mediated through NPY-dependent pathways. Moreover, PNX altered the transcription of Kiss, NKB, and pDYN, key components of the GnRH pulse generator, and modulated LHβ mRNA expression in the pituitary. Changes in the LH and FSH concentrations further supported a receptor-specific mechanism of PNX action. The developed hypothalamo–pituitary OOC model proved valuable for studying neuroendocrine control of reproduction. This system offers a physiologically relevant and ethically sustainable alternative to in vivo experiments, enabling precise investigations of molecular and hormonal mechanisms within the gonadotrophic axis.

Targeted delivery of therapeutics to bladder cancer is crucial for optimizing therapeutic efficacy and minimizing side effects. In this study, a novel targeted nanocarrier system was developed to enhance bladder cancer targeted therapy by modifying liposomes with 4-carboxyphenylboronic acid (CPBA), enabling selective binding with sialic acid residues overexpressed on bladder cancer cells. To further improve therapeutic outcomes, we employed a combination therapy based on chemotherapy and immunotherapy to both eliminate tumor cells and activate antitumor immune responses. We fabricated tumor-targeting liposome-chitosan-CPBA (LPCB) nanoparticles coloaded with doxorubicin (Dox), a chemotherapeutic agent, and resiquimod (R848), a toll-like receptor (TLR) 7/8 agonist that stimulates antitumor immunity. LPCB nanoparticles encapsulating Dox and R848 (LPCBDR) demonstrated enhanced binding to bladder tumor cells (T24, MB49) and cytotoxicity compared to nontargeted (non-CPBA incorporated) nanoparticles. LPCBDR nanoparticles also showed enhanced activation of murine dendritic cell (DC) populations characterized by the upregulation of costimulatory molecules. In vivo biodistribution studies with Cy7-labeled nanoparticles confirmed preferential tumor accumulation of LPCB NPs compared to nontargeted nanoparticles. Therapeutic efficacy using MB49 subcutaneous tumor model revealed that LPCBDR treatment group significantly reduces tumor volume compared to nontargeted nanoparticles and free drugs. Flow cytometric analysis of tumor and spleen samples further showed robust activation of Natural Killer (NK) cells, CD4⁺ T cells, and CD8⁺ T cell effector functions. Combined results demonstrate that sialic acid targeting LPCBDR nanoparticles offers a promising drug delivery platform for bladder cancer therapy.

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.

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.