ACS Biomaterials Science & Engineering最新文献

Matrix stiffness is a key factor in breast cancer progression, but its impact on cell function and response to treatment is not fully understood. Here, we developed a stiffness-tunable hydrogel-based three-dimensional system that recapitulates the extracellular matrix and physiological properties of human breast cancer in vitro. Adjusting the ratio of GelMA to PEGDA in the hydrogel formulation enabled the fine-tuning of matrix stiffness across a range of 7 to 52 kPa. Utilizing this three-dimensional (3D) hydrogel platform for a breast cancer cell culture has enabled precise functional evaluations. Variations in matrix stiffness resulted in significant changes in the morphology of breast cancer cells after 2 weeks of incubation. The analysis of transcriptomic sequencing revealed that the 3D microenvironment significantly changed the expression of a wide panel of transcriptomic profiles of breast cancer cells in various matrix stiffness. Gene Ontology analysis further suggested that specific biological functions could potentially be linked to the magnitude of the matrix stiffness. According to our findings, extracellular matrix rigidity modulates the sensitivity of breast cancer cells to paclitaxel and adriamycin. Notably, the expression of ABCB1 and YAP1 genes may be upregulated in the 3D culture environment, potentially contributing to the increased drug resistance observed in breast cancer cells. This work aims to establish facile adjustable hydrogels to deepen insights into matrix rigidity effects on breast cancer cells within 3D microenvironments, highlighting the critical role of extracellular matrix stiffness in modulating cell-matrix interactions.

This study explores the synergistic effects of combining titania nanotubes (TiNTs) with the biopolymer Tanfloc (TAN) to enhance the surface properties of TiNTs for biomedical applications. We investigated the interactions of blood components and human adipose-derived stem cells (ADSCs) with TiNT surfaces covalently functionalized with Tanfloc (TAN), an aminolyzed polyphenolic tannin derivative. The functionalized surfaces (TiNT-TAN) have great potential to control protein adsorption and platelet adhesion and activation. Fluorescence and scanning electron microscopy (SEM) were used to analyze platelet adherence and activation. The amphoteric nature and multiple functional groups on TAN can control blood protein adsorption, platelet adhesion, and activation. Further, the modified surface supports adipose-derived stem cell (ADSC) viability, attachment, and growth without any cytotoxic effect. The TAN conjugation significantly (****p < 0.0001) increased the proliferation rate of ADSCs compared to the TiNT surfaces.

Cerebral vascular disorders often accompany hypoxia-induced brain injury. In this study, we develop a zebrafish model of hypoxia-induced cerebral vascular injury to replicate the associated phenotypic changes, including cerebrovascular damage, neuronal apoptosis, and neurological dysfunction. We then explored the therapeutic potential of extracellular vesicles derived from Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) cultured on soy protein-coated surfaces. These vesicles demonstrated superior recovery efficacy, especially in restoring the blood–brain barrier integrity and improving neurological function. Our findings suggest that these potent therapeutic extracellular vesicles, easily produced from WJ-MSCs cultured in the presence of soy proteins, may mitigate hypoxia-induced brain injury by decreasing the severity of vascular disorder caused by oxidative stress. Protein–protein interactome analysis further suggests that multiple signaling pathways are likely involved in restoring normal neurovascular unit function.

The rapid increase in the number of stimuli-responsive polymers, also known as smart polymers, has significantly advanced their applications in various fields. These polymers can respond to multiple stimuli, such as temperature, pH, solvent, ionic strength, light, and electrical and magnetic fields, making them highly valuable in both the academic and industrial sectors. Recent studies have focused on developing hydrogels with self-healing properties that can autonomously recover their structural integrity and mechanical properties after damage. These hydrogels, formed through dynamic covalent reactions, exhibit superior biocompatibility, mechanical strength, and responsiveness to stimuli, particularly pH changes. However, conventional hydrogels are limited by their weak and brittle nature. To address this, ionizable moieties within polyelectrolytes can be tuned to create ionically cross-linked hydrogels, leveraging natural polymers such as alginate, chitosan, hyaluronic acid, and cellulose. The integration of ionic liquids into these hydrogels enhances their mechanical properties and conductivity, positioning them as significant self-healing agents. This review focuses on the emerging field of stimuli-responsive ionic-based hydrogels and explores their potential in dermal applications and tissue engineering.

Cisplatin (CDDP) is one of the most commonly used chemotherapeutic agents for solid tumors and hematologic malignancy. However, its therapeutic outcomes have remained unsatisfactory due to severe side effects, a short elimination half-life, the emergence of drug resistance, and the induction of metastasis. Combination with other chemotherapeutic agents has been proposed as one strategy to address the drawbacks of CDDP-based therapy. Therefore, this study aimed to boost the antitumor efficacy of cisplatin (CDDP) with a PI3K/mTOR dual inhibitor, dactolisib (BEZ), via a carrier-free codelivery system based on the self-assembly of the coordinated CDDP–BEZ. The synthesized CDDP–BEZ nanoparticles (NPs) possess sensitive pH-responsiveness, facilitating the delivery of both drugs to cancer cells. CDDP–BEZ NPs specifically enhanced cytotoxicity in cancer cells due to the synergy between cisplatin and dactolisib, resulting in augmented DNA damage, activation of mitochondria-dependent apoptosis, and increased inhibition on the PI3K/mTOR signaling axis. The inhibition of tumor migration and metastasis by CDDP–BEZ NPs was observed both in vitro and in vivo. Our data suggest that CDDP–BEZ NPs could serve as a safe and effective platform to maximize the synergy between both drugs in combating cancer, presenting a strategy to promote the therapeutic efficacy of platinum-based chemotherapeutic agents by combining them with PI3K inhibitors.

Background: The voluntary recall and ban of several textured breast implant models worldwide, secondary to their association with Breast Implant-Associated Anaplastic Large Cell Lymphoma, has limited the key benefit of a textured surface─positional stability. We have engineered a Positionally Stable Smooth Implant (PSSI) containing millimeter-scaled cylindrical wells on the implant surface for capsule ingrowth and device stabilization. Objectives: To evaluate the long-term positional stability of PSSI designs in vivo and characterize capsule formation. Methods: Miniature breast implants were manufactured using poly(dimethylsiloxane). PSSI were designed with various dimensions of well width, depth, and number. Comparison groups consisted of smooth and textured implants. Six sterilized implants per group were implanted subcutaneously into the bilateral dorsa of Sprague–Dawley rats. Implant rotation was measured with MicroCT every 2 weeks. Implant-capsule units were explanted at 3 months for histological analysis. Results: All PSSI groups exhibited significantly less cumulative positional rotation than smooth implants (p < 0.05), with stability comparable to that of textured implants. Upon explantation, microCT and gross examination revealed notable capsule ingrowth within the PSSI wells. Histological evaluation of foreign body response showed significantly fewer pro-inflammatory M1 macrophages in the PSSI capsules compared to the textured control. Additionally, myofibroblast expression, which is implicated in capsular contracture, was significantly lower in both the PSSI and textured groups compared to smooth implants. Conclusions: This novel smooth-surface breast implant design provided equivalent positional stability and reduced pro-inflammatory M1 macrophage expression compared to textured implants. These results suggest a promising, safer alternative to textured implants for inducing positional stability.

Oral health problems, particularly tooth defects, can significantly affect people’s quality of life and overall well-being. The development of titanium (Ti) dental implants has largely replaced natural tooth roots to prevent periodontal and gastrointestinal diseases. However, challenges such as postoperative bacterial infections and poor osseointegration continue to hinder progress in dental implant technology. To tackle these issues, we used hydroxypropyl trimethylammonium chloride chitosan (HACC) and gallic acid-modified gelatin (GAG) to create extracellular matrix (ECM) coatings on titanium using layer-by-layer self-assembly. GAG showed better water solubility at room temperature, being over 99.0 times more soluble than regular gelatin. In vivo and in vitro analyses of the ECM coatings revealed their antibacterial properties and their ability to promote osteogenic differentiation, resulting in over 31.5 times more calcareous deposits than Ti. This strategy shows potential for improving oral health and reducing the complications associated with dental implants in clinical settings.

Objective: This study aimed to investigate the effects of a sustained-release composite containing gelatin methacryloyl (Gel) and kaempferol (Ka, K) on experimental periodontitis symptoms in rats. Methods: Forty 6-week-old male rats were randomly assigned to four treatment groups in a specific pathogen-free (SPF) environment: Control group (C), periodontitis model group (M), Gel alone group (G), and Gel_Ka composite-treated group (G_K). Treatment effects on the periodontal status of bilateral maxillary second molars in each rat group were assessed by micro-CT imaging and histology. Immunohistochemistry staining was employed to examine the effects on expression levels of inflammatory factors IL-6 and MMP9 (associated with M1 macrophages) and of the anti-inflammatory factor CD206 (associated with M2 macrophages). Additionally, treatment effects on oral and intestinal microbial communities were analyzed through 16S rDNA sequencing. Results: Local injection treatment with the G_K composite hydrogel effectively suppressed alveolar bone resorption and reduced periodontal attachment loss and inflammation infiltration in rats with periodontitis. It reduced the expression of inflammatory factors MMP9 and IL-6 but increased the anti-inflammatory factor CD206, and it also increased the abundance of gut microbial communities producing short-chain fatty acids. Conclusion: Local treatment with the sustained-release G_K hydrogel composite demonstrates a substantial antiperiodontitis effect in rats by locally attenuating inflammation and is associated with enhancing the microbial composition of intestinal flora, thus aiding in mitigating the inflammatory progression of experimental periodontitis.

Fibrocartilage decellularized extracellular matrix (dECM) is a promising alternative material for damaged fibrocartilage repair and replacement due to its biomimetic gross morphology and internal microstructure. However, the alterations in the microstructure and micromechanical properties of fibrocartilage after decellularization interfere with the macroscopic functional application of the scaffold. Therefore, this study aims to present an analytical atlas of the microstructure and micromechanics of the fibrocartilaginous dECM scaffold to elucidate the effect of decellularization treatment on the macroscopic function of the scaffold. The fibrocartilage dECM was prepared using the temporomandibular joint (TMJ) disc as the model, and its durability was evaluated under three functional states (physiological, physiological limit, and beyond the limit). The macroscopic function of different fibrocartilage dECM exhibits notable differences, which are attributed to the destruction of the multilevel collagen structure. This process involves unwinding triple-helix tropocollagen molecules, destroying collagen fibril D-periodicity, expanding collagen fiber bundle curling, and loosening of the collagen fiber network. The impairment of multiscale collagen structures degrades the cross-scale mechanical modulus and energy dissipation of dECM from the triple helix molecules to the fibril level to the fiber bundle that extends to the fiber network. This study provides important data for further optimizing decellularized fibrocartilage scaffolds and evaluating their translational potential.

Infected diabetic wounds represent a significant challenge in clinical care due to persistent inflammation and impaired healing. To address these issues, the development of novel wound dressings with both antibacterial and reactive oxygen species (ROS) scavenging properties is essential. Herein, we prepare a novel wound dressing composed of Cu_2–xO nanoparticles decorated on Ti₃C₂ MXene (Cu_2–xO@Ti₃C₂) and integrate it into a poly(vinyl alcohol) (PVA) matrix to form electrospun nanofibers (Cu_2–xO@Ti₃C₂@PVA). Cu_2–xO@Ti₃C₂ exhibits remarkable photothermal conversion efficiency and effective ROS scavenging properties. In vitro experiments demonstrated that Cu_2–xO@Ti₃C₂ effectively kills bacteria upon near-infrared (NIR) irradiation, which can be attributed to the photothermal therapy (PTT) effect of Ti₃C₂. At the same time, the ROS scavenging abilities of both Ti₃C₂ and Cu_2–xO endow Cu_2–xO@Ti₃C₂ with significant in vitro anti-inflammatory effects. As a promising wound dressing, in vivo studies validated the high efficacy of Cu_2–xO@Ti₃C₂@PVA in promoting hemostasis, exerting antibacterial activity, reducing inflammation, and accelerating the healing process of diabetic wounds. This innovative approach provides a comprehensive solution to the multifaceted challenges of diabetic wound healing and paves the way for improved clinical outcomes.