ACS Biomaterials Science & Engineering最新文献

Various tissues have oriented collagen structures that confer mechanical strength and stability. However, creating models that precisely mimic the size and direction of these tissues remains challenging. In the present study, we developed a collagen tissue with multiscale and multidirectional controlled orientation using fluidic devices prepared using three-dimensional (3D) printing technology. Two types of fluidic channels were fabricated: a one-directional "horizontal orientation model" and vertical protrusions added to create a two-directional "vertical/horizontal orientation model". A type I collagen solution, mixed with or without cells, was introduced into the fluidic channel and gelled. As a result, in the horizontal orientation model, collagen fibrils and fibers were oriented by the flow. Both the fibroblasts and stem cells were aligned parallel to the flow along the collagen structure. In the vertical/horizontal orientation model, both the horizontal and vertical parts confirmed the orientation of collagen fibrils, fibers, and fibroblasts in both directions. Observation of the model at the nanoscale level using scanning electron microscopy (SEM) can explain the collagen orientation mechanism at the molecular and fibril levels. Prior to full gelation, collagen molecules and fibrils align parallel to the flow owing to the influence of flow and channel wall effects. This wall effect, starting from the outer channel wall, creates a gelated collagen "wall" toward the inside of the channel. Collagen fibrils aggregate into collagen fibers. In our experiments focusing on collagen contraction, the cell orientation was also described. As cells proliferate in response to the contact guidance of collagen fibrils and fiber orientation, focal adhesions and F-actin are activated and organize anisotropic traction forces that, in turn, drive cell orientation. Therefore, our method enables the customization of models with the desired tissue-specific orientations, thereby advancing future possibilities in tissue engineering.

Reconstructing auricular tissue is challenging because ear cartilage has few blood vessels and limited regenerative capacity. Traditional methods that utilize autologous costal cartilage or synthetic polymers often lead to donor site morbidity and suboptimal biocompatibility. In this study, we introduce 3D-printed scaffolds composed of decellularized human cartilage-derived bioink combined with polycaprolactone (PCL), designed to enhance both tissue regeneration and mechanical stability. The decellularization process effectively removed cellular components while preserving glycosaminoglycan and total collagen, comparable to those in native cartilage. We formulated the bioink by incorporating decellularized human cartilage particles into hyaluronic acid and carboxymethyl cellulose gels, optimizing the rheological properties for 3D printing. In vitro tests demonstrated that the decellularized human cartilage-derived bioink exhibited no cytotoxicity and facilitated the migration and chondrogenic differentiation of human adipose-derived stem cells. We fabricated 3D-printed scaffolds using this bioink combined with PCL and evaluated their performance in rabbits over a one-year implantation period. Our results indicated that the scaffolds maintained structural integrity throughout the year and exhibited significant neovascularization and chondrogenesis. Histological analysis revealed increased blood vessel formation in scaffolds with higher ratios and greater decellularized cartilage content with notable differences observed across varying porosities. These findings suggest that 3D-printed scaffolds with decellularized human cartilage-derived bioink and PCL offer a promising approach for auricular reconstruction, potentially improving outcomes for patients with microtia.

The increasing prevalence of carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii (XDR-Ab) poses a critical challenge in treating hospital-acquired pulmonary infections. In this study, we developed a biomimetic neutrophil membrane-coated nanoparticle system, NM@PCN-TIG, for the targeted delivery of tigecycline (TIG). The system utilizes the porphyrin-based metal-organic framework (MOF) PCN-224 as the core of the nanoparticle, encapsulating TIG and coated with a neutrophil membrane (NM) to enhance immune evasion and targeting of infection sites. Its loading efficiency, controlled release properties, cytotoxicity, and bactericidal activity under ultrasound mediation were systematically evaluated in vitro and in vivo. Our results demonstrated that NM@PCN-TIG significantly enhanced the bactericidal efficacy of TIG, increased reactive oxygen species (ROS) production, and promoted macrophage polarization toward an anti-inflammatory phenotype. This innovative biomimetic TIG nanosystem shows great potential as a platform for addressing XDR-Ab-induced pneumonia.

Integration of a high-entropy alloy (HEA) with nanozyme activity and a piezoelectric material with piezoelectricity is a promising strategy to develop a novel biofunctional material for the repair of infectious bone defects. Herein, a heterojunction of HEA (FeMnMoRuIr) and zinc sulfide (ZnS) (HEA@ZnS) is synthesized that exhibits enhanced piezoelectricity and nanozyme activities. Moreover, a piezoelectric hydrogel containing zein, sodium alginate, and HEA@ZnS (ZeAHZ) with antibacterial properties and pro-osteogenic capability is fabricated. Under acidic conditions, triggered by ultrasound, the piezoelectric effect of ZeAHZ enhances peroxidase-like activity and sonodynamic efficiency that produces a large amount of reactive oxygen species (ROS, ·O₂^- and ·OH) for collaboratively eliminating bacteria. Moreover, the superoxide-like activity and piezoelectric effect-enhanced catalase-like activity of ZeAHZ scavenge ROS (·O₂^- and H₂O₂) and produce oxygen due to the cascade reaction, which provides a favorable microenvironment for cell growth. Further, the piezoelectric effect of ZeAHZ generates electrical stimulation that significantly promotes osteoblast proliferation and differentiation. This study opens up a new path for designing a biomaterial with the capability of production/elimination of ROS and pro-osteogenesis by electrical stimulation, and ZeAHZ has great potential for accelerating bone regeneration.

Hemodynamic fluctuations at vessel bifurcation impact the development of atherosclerosis and aneurysms. A novel glass capillary tube-based lithography-free technique was used for fabricating vessel bifurcations with stenosis and aneurysm at the junction of bifurcation to determine the endothelial response to arterial shear rates in vitro. At variable shear rates of 1-2000 s^-1, representative of conditions in the aorta, the endothelial cell responses under flow disturbances encountered in stenosed and aneurysmal vessels were modeled. Mechanical disturbances induce greater endothelial activation at stenosis, while increased VE-cadherin expression deters activation at dilations. The endothelial responses to disturbed flow were better observed at the area of bifurcation, where the increase in shear forces and reduced pressure marginally compensated for cellular activation. The comparative model was established using an image analysis approach for the assessment of endothelial responses toward disease progression at bifurcations. No significant differences in endothelial markers were observed under inflammatory stress and physiologically relevant mechanical stresses due to compensatory effects of inflammatory cytokines inducing NF-κβ activation, as seen using this frugal approach.

Liver disorders like hepatitis, cirrhosis, and hepatocellular carcinoma present a significant global health challenge, with high morbidity and mortality rates. Key factors contributing to liver disorders include inflammation, oxidative stress, and apoptosis. Due to their multifaceted action, natural compounds are promising candidates for mitigating liver-related disorders. Research studies revealed the antioxidant, anti-inflammatory, and detoxifying properties of natural compounds like curcumin, glycyrrhizin, and silymarin and their potential for liver detoxification and protection. With advancements in nanotechnology in drug delivery, natural compounds have improved stability and targetability, thereby enhancing their bioavailability and therapeutic efficiency. Further, recent advancements in genomics and an increased understanding of genetic factors influencing liver disorders and the hepatoprotective effects of natural agents made way for personalized medicine. Moreover, combinatorial therapy with natural products, synthetic drugs, or other natural agents has improved therapeutic outcomes. Even though clinical trials have confirmed the efficiency of natural compounds as hepatoprotective agents, several challenges remain unanswered in their translation to clinical practice. Therefore, it is logical to integrate natural compounds with nanotechnology and genomics to further advance hepatoprotection. This review gives an overview of the substantial progress made in the field of hepatoprotection, with specific emphasis on natural compounds and their integration with nanotechnology and genomics. This provides valuable insights for future research and innovations in developing therapeutic strategies for liver disorders.

Cancer is one of the leading causes of mortality worldwide. Nanomedicines have significantly improved life expectancy and survival rates for cancer patients in current standard care. However, recurrence of cancer due to metastasis remains a significant challenge. Vaccines can provide long-term protection and are ideal for preventing bacterial and viral infections. Cancer vaccines, however, have shown limited therapeutic efficacy and raised safety concerns despite extensive research. Cancer vaccines target and stimulate responses against tumor-specific antigens and have demonstrated great potential for cancer treatment in preclinical studies. However, tumor-associated immunosuppression and immune tolerance driven by immunoediting pose significant challenges for vaccine design. In situ vaccination represents an alternative approach to traditional cancer vaccines. This strategy involves the intratumoral administration of immunostimulants to modulate the growth and differentiation of innate immune cells, such as dendritic cells, macrophages, and neutrophils, and restore T-cell activity. Currently approved in situ vaccines, such as T-VEC, have demonstrated clinical promise, while ongoing clinical trials continue to explore novel strategies for broader efficacy. Despite these advancements, failures in vaccine research highlight the need to address tumor-associated immune suppression and immune escape mechanisms. In situ vaccination strategies combine innate and adaptive immune stimulation, leveraging tumor-associated antigens to activate dendritic cells and cross-prime CD8+ T cells. Various vaccine modalities, such as nucleotide-based vaccines (e.g., RNA and DNA vaccines), peptide-based vaccines, and cell-based vaccines (including dendritic, T-cell, and B-cell approaches), show significant potential. Plant-based viral approaches, including cowpea mosaic virus and Newcastle disease virus, further expand the toolkit for in situ vaccination. Therapeutic modalities such as chemotherapy, radiation, photodynamic therapy, photothermal therapy, and Checkpoint blockade inhibitors contribute to enhanced antigen presentation and immune activation. Adjuvants like CpG-ODN and PRR agonists further enhance immune modulation and vaccine efficacy. The advantages of in situ vaccination include patient specificity, personalization, minimized antigen immune escape, and reduced logistical costs. However, significant barriers such as tumor heterogeneity, immune evasion, and logistical challenges remain. This review explores strategies for developing potent cancer vaccines, examines ongoing clinical trials, evaluates immune stimulation methods, and discusses prospects for advancing in situ cancer vaccination.

Colorectal cancer (CRC) studies in vitro have been conducted almost exclusively on 2D cell monolayers or suspension spheroid cultures. Though these platforms have shed light on many important aspects of CRC biology, they fail to recapitulate essential cell-matrix interactions that often define in vivo function. Toward filling this knowledge gap, synthetic hydrogel biomaterials with user-programmable matrix mechanics and biochemistry have gained popularity for culturing cells in a more physiologically relevant 3D context. Here, using a poly(ethylene glycol)-based hydrogel model, we systematically assess the role of matrix stiffness and fibronectin-derived RGDS adhesive peptide presentation on CRC colony morphology and proliferation. Highlighting platform generalizability, we demonstrate that these hydrogels can support the viability and promote spontaneous spheroid or multicellular aggregate formation of six CRC cell lines that are commonly utilized in biomedical research. These gels are engineered to be fully degradable via a "biologically invisible" sortase-mediated reaction, enabling the triggered recovery of single cells and spheroids for downstream analysis. Using these platforms, we establish that substrate mechanics play a significant role in colony growth: soft conditions (∼300 Pa) encourage robust colony formation, whereas stiffer (∼2 kPa) gels severely restrict growth. Tuning the RGDS concentration did not affect the colony morphology. Additionally, we observe that epidermal growth factor receptor (EGFR) signaling in Caco-2 cells is influenced by adhesion ligand identity─whether the adhesion peptide was derived from collagen type I (DGEA) or fibronectin (RGDS)─with DGEA yielding a marked decrease in the level of downstream protein kinase phosphorylation. Taken together, this study introduces a versatile method to culture and probe CRC cell-matrix interactions within engineered 3D biomaterials.

To recapitulate prostate cancer metastasis, DU145 cells were cultured in a hyaluronic acid-based, bio-orthogonally constructed, protease-degradable hydrogels. In the presence of a covalently conjugated integrin-binding peptide (GRGDSP), DU145 cells formed tumoroids and exhibited small protrusions. Upon addition of soluble transforming growth factor beta 1 (TGFβ1), cells underwent morphological changes to form extended interconnected cellular networks. Contrarily, in RGD-free hydrogels, cells maintained spherical structures even in the presence of TGFβ1. In RGD-conjugated hydrogels, TGFβ1 induced nuclear localization of SMAD2/3, upregulating a wide range of TGFβ1 target genes and proteins. Prolonged exposure to TGFβ1 led to matrix remodeling and induced epithelial-to-mesenchymal transition in DU145 cells, with loss of epithelial markers and gain of mesenchymal markers. A pharmacological inhibitor of TGFβRI/ALK5, SB-431542, attenuated TGFβ1-induced morphological changes, abrogated nuclear localization of SMAD2/3, and restored the expression of key epithelial markers. Our findings highlight the cooperative role of TGFβ1 signaling and integrin-binding peptide in the acquisition of an aggressive phenotype and the promotion of tumor progression.