ACS Biomaterials Science & Engineering最新文献

Glioma is a highly malignant tumor of the central nervous system characterized by high morbidity, substantial drug resistance, and poor prognosis. Therapeutic challenges stem from the invasive growth of tumor cells, limited drug penetration through the blood–brain barrier (BBB), and widespread drug resistance induced by the tumor microenvironment. In recent years, biotherapeutic strategies based on the biological characteristics of circular RNAs (circRNAs) have emerged as promising avenues for glioma management. circNEFM functions as a competitive endogenous RNA (ceRNA) by sponging miR-1248 and miR-1236, thereby upregulating the expression of BCL6B and C1orf115. This molecular mechanism of circNEFM effectively inhibits tumor proliferation while sensitizing glioma cells to chemotherapy. However, conventional delivery systems have inherent limitations, including short systemic circulation time and inadequate local drug concentration. To overcome these challenges, in this study, we engineered a multifunctional GelMA hydrogel scaffold system that integrates three key advantages: the innate ability of exosomes to traverse the BBB while protecting their cargo from enzymatic degradation, aptamer-mediated precise tumor targeting, and the sustained release profile of GelMA hydrogels. This composite scaffold exhibited excellent biomechanical properties and enabled the controlled release of engineered exosomes loaded with circNEFM (exo-circNEFM). Notably, aptamer-functionalized exosomes exhibited enhanced specificity to glioma cells, leading to significant inhibition of cell proliferation through circNEFM-mediated pathways and effective reversal of chemoresistance. This innovative therapeutic platform represents a novel technological solution with considerable translational potential for glioma treatment.

Water-responsive materials represent a class of stimuli-responsive “smart” materials that have become a focal point of recent research in recent years. Their unique ability to undergo reversible shape changes in response to water or humidity makes them highly versatile for various applications. Inspired by natural phenomena such as the hygroscopic movements of plant fibers and the supercontraction of spider silk, these materials exhibit excellent shape adaptability, phase transition, and wet tissue adhesion capabilities. Their ability to thrive in the aqueous environment, where saliva and gingival crevicular fluid provide a dynamic medium, makes them particularly promising for applications in oral medicine. This review, drawing on literature primarily from the past decade, comprehensively discusses the mechanisms, building blocks, and current advancements in water-responsive materials, with a focus on their potential in oral drug delivery, tissue engineering, and wound management. Key applications include alveolar bone regeneration, chronic wound healing, periodontitis treatment, and hemostatic dressings, where their shape adaptability, biocompatibility, and biodegradability address critical clinical challenges. Despite their potential, the application of water-responsive materials in oral medicine remains underexplored, highlighting the need for further research to optimize their design and functionality. By integrating insights from recent studies, this review aims to provide a foundation for the development of next-generation water-responsive materials tailored to meet the unique demands of oral healthcare.

Calcific aortic valve disease is an active process characterized by compromised endothelial integrity and obstructive calcific lesions, whose emergence is poorly understood. Valves experience an equiaxial stretch in regions susceptible to calcific lesion formation, but mechanobiological mechanisms are not tested. Here, we analyze how cyclic strain regulates interstitial (PAVIC) and endothelial (PAVEC) interactions in 3D environments. Equiaxial cyclic strain was applied to 3D cultures of PAVEC, PAVIC, or PAVEC–PAVIC cocultures over 7 days in control or osteogenic media (OGM) conditions. Cell phenotype and tissue remodeling were quantitatively compared to mechanically strained (anchored) but nonstretched controls. Cyclic stretch shifted PAVIC from myofibroblastic to osteogenic phenotype with OGM, while in PAVEC, the cyclic stretch increased apoptosis. Intriguingly, we determined that PAVEC–PAVIC in coculture with OGM develop raised 3D calcified lesions (∼25–50% of gel thickness) similar to lesions seen in vivo. Lesions contained radially reoriented collagen fibers with similarly aligned PAVIC, increased local PAVEC density, and decreased PAVEC cell area. The cyclic stretch synergistically increased the lesion number and height but not the projected area. The cyclic stretch enhanced osteogenic differentiation (Runx2 and OPN) but not myofibroblastic differentiation (aSMA) in cocultures. It significantly increased VE-cadherin and eNOS and reduced VCAM1, but with OGM, the eNOS expression reduced. Finally, we determined that ROCK inhibition abolished 3D lesion formation and myofibroblastic and osteoblastic differentiation, supporting the idea that these integrated behaviors were mechanobiologically mediated by cell migration and/or contractility. Our results identify that the 3D cyclic stretch induces emergent PAVEC–PAVIC interactions not capturable in less complex environments that together control 3D calcific lesion morphology.

Autologous fat transplantation (AFT) remains limited by low graft survival rates due to insufficient vascularization and extracellular matrix (ECM) support. Here, we developed an adipose tissue regeneration unit (ATRU) system combining three key cellular components (adipose-derived stem cells, ADSCs; human umbilical vein endothelial cells, HUVECs; and fibroblasts, FBs) within a porous gelatin methacryloyl (pGelMA) hydrogel microenvironment. Through controlled coculture in microwell plates, this system generated functional microtissues, demonstrating synergistic effects: ADSCs provided adipogenic potential; HUVECs enabled vascular network formation, and FBs facilitated ECM deposition. Comprehensive in vitro characterization confirmed enhanced cell viability, adipogenic differentiation, and collagen production. In vivo implantation in nude mice revealed enhanced performance of ATRU constructs compared to ADSC-only controls, with histological and immunohistochemical analysis showing: (1) a 1.14-fold increase in adipose tissue area, (2) a 1.55-fold increase in the number of CD31⁺ blood vessels per field of view, and (3) substantially elevated type III collagen deposition. The incorporation of pGelMA provided a biocompatible and porous scaffold, facilitating cell viability, nutrient diffusion, and structural integration with the host tissues. These results highlight the capacity of the ATRU strategy to simultaneously address the critical challenges of vascularization, ECM remodeling, and volume retention in fat grafting, offering a promising proof-of-concept platform to guide further preclinical optimization for breast reconstruction and aesthetic augmentation.

Osteoarthritis, affecting millions globally each year, results in progressive joint function deterioration. The key to osteoarthritis treatment is the repair of damaged cartilage, while cartilage is poor at self-regeneration. Although autologous and allogeneic cartilage implantations are currently used to treat cartilage injuries, their clinical application is constrained by poor biocompatibility and limited donor availability. Tissue-engineered scaffolds have emerged as a promising strategy for cartilage repair, but their clinical translation is often limited by inadequate chondrogenic differentiation and inflammation control. In this study, we fabricated a biomimetic gelatin/graphene oxide (GO) composite cryogel scaffold for cartilage regeneration applications. This cryogel combines the advantages of gelatin and graphene oxide, exhibiting excellent mechanical properties, biocompatibility, and cell adhesion capacity while inducing chondrogenesis. After being implanted in a rat cartilage defect model, this cryogel effectively promoted structural and functional cartilage repair within 4 weeks. Furthermore, we investigated the underlying regenerative mechanism and demonstrated that this cryogel promotes cartilage regeneration by inducing chondrogenesis and suppressing oxidative phosphorylation. Collectively, these findings demonstrate that this cryogel represents a promising therapeutic approach for osteoarthritis resulting from cartilage injury.

Biocompatible hydroxyapatite (HA) is a biomaterial widely used in the regeneration and replacement of dental and bone tissue. On these HA surfaces, complex multicellular communities known as biofilms are established by pathogenic microorganisms, contributing to 75% of all bacterial infections and presenting a significant public health concern. Among the various charged polymers, zwitterionic polymers are commonly used for antifouling applications due to their ability to form a strong hydration layer. In contrast, charged polymers like polyampholytes with both positively and negatively charged groups remain largely unexplored for this application. Polyampholytes can be modified to be neutral, cationic, or anionic, as they are composed of two monomers with opposite charges. In this study, we aim to investigate the preparation of polyampholytes with different charges through Reversible Addition–Fragmentation chain Transfer (RAFT) polymerization, coating these polymers onto HA discs and evaluating their antifouling capabilities using bacterial adhesion experiments. We synthesized charged polyampholytes using [2-(methacryloyloxy)ethyl]trimethylammonium chloride (MAETMA) and sodium-p-vinylbenzenesulfonate (VBS), which are cationic and anionic monomers, respectively, in a DI water/dioxane medium via RAFT polymerization. Next, HA discs were coated with a series of synthesized charged polymers, resulting in surfaces with systematically tuned net charges ranging from fully positive to fully negative, labeled as HAP1-HAP5. Cytotoxicity assessments using NIH-3T3 fibroblast cells confirmed the biocompatibility of the polymer-coated HA surfaces. To confirm the antifouling property, adherence studies of Streptococcus mutans (S. mutans), a bacterium that causes dental caries (tooth decay) and dental plaque, were analyzed using a scanning electron microscope (SEM). Among all samples, HAP3 exhibited the minimum bacterial adhesion and the most effective resistance to protein adsorption, significantly outperforming the uncoated HA control.

The glomerular filtration barrier (GFB), composed of glomerular endothelial cells (GEnCs), the glomerular basement membrane (GBM), and podocytes, serves as a highly selective interface regulating fluid and solute exchange between blood and urine. This review synthesizes current understanding of the anatomy, developmental biology, and molecular signaling pathways that govern the structure and function of each GFB component. Key regulators such as vascular endothelial growth factor (VEGF), nephrin, integrins, and laminins are discussed in the context of barrier formation, maintenance, and injury response. Advanced imaging methods including electron microscopy, intravital microscopy, and super-resolution techniques are reviewed for their roles in characterizing nanoscale GFB architecture. To bridge glomerular biology with engineering applications, we critically evaluate how these insights inform the design of bioinspired hemodialysis (HD) membranes. Strategies such as endothelialization, extracellular matrix (ECM) coatings, and triculture systems are explored, alongside recent developments in glomerular-inspired membranes and organ-on-chip models. We also address the practical challenges of translating these biological features into scalable, hemocompatible dialysis technologies. By integrating advances in cell biology, materials science, and microfluidic modeling, this review provides a framework for the development of next-generation dialysis membranes that more closely replicate native kidney filtration.

Uniform TNT growth on complex geometries, such as screw-threaded surfaces, is challenging due to non-uniform electric fields in anodization. This study examines TNT growth on screw threads and dental implants, intending to determine the impact of geometry on the electric field distribution using Finite Element Analysis (FEA). Simulation results showed that the electric field intensity was highly variable, with increased values on teeth and decreased values on the root and flank, causing nonuniform growth of TNTs. Experimental anodization coupled with Field-Emission Scanning Electron Microscopy (FESEM) affirmed the findings with shorter TNTs on the root and more stable growth on the teeth and flanks. TNT diameter correlated with applied DC voltage, while TNT length, with variations of 6 μm, was highly sensitive to the cathode design. To solve the problem, a new multicathode anodization cell was developed to produce a uniform field distribution. By adjustment of the cathode-to-anode (CA) area ratio, it was discovered that a CA of 1 yielded the optimal results, and this resulted in uniform TNT growth in all regions. Lower CAs (e.g., 0.5:1) resulted in low field strength and incomplete TNT growth, and high CAs (2:1) led to over-dissolution and structural damage. Optimization on actual dental implants using the CA 1 setup and two-stage anodization process yielded a more controlled TNT length and diameter. The final TNT morphology on the dental implant had TNT length variations of 0.4 μm with a 100 nm diameter. These results reveal the importance of the electric field uniformity in anodizing implants with complex geometries. The proposed multicathode design presents an efficient and scalable solution for uniform TNT layer deposition on dental implants and similar freeform curved surfaces.

Osteosarcoma (OS), an extremely aggressive bone cancer that primarily occurs in children and teenagers, continues to pose critical clinical challenges due to its high propensity for metastasis, resistance to conventional therapies, and lack of specific biomarkers for early detection. Despite advances in surgical techniques and chemotherapeutic regimens, patient outcomes remain suboptimal, predominantly because conventional two-dimensional (2D) cell culture systems do not accurately mimic the intricate tumor microenvironment (TME), which often results in limited success when translating preclinical results to clinical success. In response to the shortcomings, the field has shifted toward three-dimensional (3D) culture systems, which more accurately mimic the spatial, mechanical, and biochemical characteristics of native OS TME. This review systematically examines the evolution and current state of 3D OS models, with a particular focus on scaffold-based systems. These models, utilizing biomimetic scaffolds provide enhanced platforms for studying tumor–stroma interactions, drug responses, and chemoresistance. It also briefs the use of scaffold-free spheroid models, which, despite their utility in replicating certain aspects of tumor heterogeneity and cell–cell interactions, are limited in their ability to fully emulate the in vivo microenvironment. The review further discusses technical and translational hurdles, such as optimizing scaffold properties and integrating patient-derived cells, which must be addressed to realize the full potential of 3D models in personalized medicine and drug discovery. The significant advancement of scaffold-based 3D OS models offers a more physiologically relevant platforms to bridge the gap between experimental research and clinical application in chemotherapy.