ACS Biomaterials Science & Engineering最新文献

Sperm cryopreservation is important for many individuals across the globe. Recent studies show that vitrification is a valuable approach for maintaining sperm quality after freeze–thawing processes and requires sub-microliter to microliter volumes. A major challenge for the adoption of vitrification in fertility laboratories is the ability to pipet small volumes of sample. Here, we present an open droplet generator that leverages open-channel microfluidics to passively generate sub-microliter to microliter volumes of purified human sperm samples and preserves sperm kinematics. We conclude that our platform is compatible with human sperm, an important foundation for future implementation of vitrification in fertility laboratories.

Taking advantage of their innate roles as antibacterial strategies, the dual activity of photobiomodulation (PBM) and nitric oxide (NO) was combined to provide a tunable, on-demand chronic wound therapeutic. S-nitrosothiol-modified mesoporous silica nanoparticles (RSNO-MSNs) were doped into polyurethane (PU) to demonstrate preliminary utility as an antibacterial wound dressing treatment for chronic wounds. Photoinitiated and resultant NO-release kinetics and payloads were evaluated at 405, 430, and 530 nm for multiple irradiances. The use of photons and the NO-releasing MSNs against common chronic wound pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, proved to be highly bactericidal. Cytocompatibility of the treatment was confirmed using human epidermal keratinocytes, a representative skin cell line.

The current lack of therapeutic approaches to demyelinating disorders and injuries stems from a lack of knowledge surrounding the underlying mechanisms of myelination. This knowledge gap motivates the development of effective models to study the role of environmental cues in oligodendrocyte progenitor cell (OPC) maturation. Such models should focus on determining, which factors influence OPCs to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Here, we introduce a hyaluronic acid (HA) hydrogel system composed of cross-linked HA containing encapsulated HA fibers with swollen diameters similar to mature axons (2.7 ± 0.2 μm). We tuned hydrogel storage moduli to simulate native brain tissue (200-2000 Pa) and studied the effects of fiber presence on OPC proliferation, metabolic activity, protein deposition, and morphological changes in gels of intermediate storage modulus (800 ± 0.3 Pa). OPCs in fiber-containing gels at culture days 4 and 7 exhibited a significantly greater number of process extensions, a morphological change associated with differentiation. By contrast, OPCs in fiber-free control gels maintained more proliferative phenotypes with 2.2-fold higher proliferation at culture day 7 and 1.8-fold higher metabolic activity at culture days 4 and 7. Fibers were also found to influence extracellular matrix (ECM) deposition and distribution, with more, and more distributed, nascent ECM deposition occurring in the fiber-containing gels. Overall, these data indicate that inclusion of appropriately sized HA fibers provides topographical cues, which guide OPCs toward differentiation. This HA hydrogel/fiber system is a promising in vitro scheme, providing valuable insight into the underlying mechanisms of differentiation and myelination.

Colorectal cancer is a lethal malignancy that begins from acquired/inherent premalignant lesions. Thus, targeting these lesions at an early stage of the disease could impede the oncogenesis and maximize the efficacy. The present work underscores a combinatorial therapy of paclitaxel (PTX) and glycyrrhizin (GL) delivered via gelatin-derived core-shell nanoparticles [AC-PCL(GL + PTX)-GNPs] for effective management of precancerous lesions. The desolvation method was adopted to prepare GL-loaded gelatin nanoparticles (GL-GNPs), which were coated with PTX and AC-PCL. The prepared NPs exhibited optimal physical attributes and had spherical morphology, as analyzed by transmission electron microscopy and field-emission scanning electron microscopy. In vitro release studies revealed sustained release for ∼96 h. Cell culture studies in HTC 116, and HT-29 cells showed synergistic action with CI < 0.9 and DRI > 1. Moreover, AC-PCL(GL + PTX)-GNPs exhibited amplified intracellular uptake and thus significantly reduced IC₅₀. Pharmacokinetic studies revealed substantiated pharmacokinetic parameters (AUC_0-∞, C_max, etc.). In vivo studies in a 1,2-dimethyl hydrazine-induced model revealed a decrease in the number of lesions, mucin depletion, and subside infiltrations. An immunohistochemical study revealed elevated expression of caspase-9 and suppressed expression of VEGF and K_i-67. Toxicity studies showed insignificant changes in systemic biomarkers along with no alterations in organ morphology and hemocompatibility. In essence, AC-PCL(GL + PTX)-GNPs render a competent and safer tactic to regulate early-stage precancerous lesions.

Pyrophosphate-stabilized amorphous calcium carbonates (PyACC) are promising compounds for bone repair due to their ability to release calcium, carbonate, and phosphate ions following pyrophosphate hydrolysis. However, shaping these metastable and brittle materials using conventional methods remains a challenge, especially in the form of macroporous scaffolds, yet essential to promote cell colonization. To overcome these limitations, this article describes for the first time the design and multiscale characterization of freeze-cast alginate (Alg)-PyACC nanocomposite scaffolds. The study initially focused on the synthesis of Alg-PyACC powder through in situ coprecipitation. The presence of alginate chains in the vicinity of the PyACC was shown to affect both the powder reactivity and the release of calcium ions when placed in water (XRD, chemical titrations). In vitro cellular assays confirmed the biocompatibility of Alg-PyACC powder, supporting its use as a filler in scaffolds for bone substitutes. In a second step, the freeze-casting process was carried out using these precursor powders with varying rates of inorganic fillers. The resulting scaffolds were compared in terms of pore size and gradient (via SEM, X-ray microtomography, and mercury intrusion porosimetry). All scaffolds exhibited a pore size gradient oriented along the solidification axis, featuring unidirectional, lamellar, and interconnected pores. Interestingly, we found that the pore size and wall thickness could be controlled by the filler rate. This effect was attributed to the in situ cross-linking of alginate chains by released Ca²⁺ ions from the fillers, which increased viscosity, affecting temperature-driven segregation during the freezing step. Different multiscale organizations of the porosity and spatial distribution of fillers (FEG-SEM) were correlated with changes in the scaffold mechanical properties (tested via uniaxial compression). With such tunable porous and mechanical properties, Alg-PyACC composite scaffolds present attractive opportunities for specific bone substitute applications.

Iron oxide-based nanoparticles are promising materials for cancer thermal therapy and immunotherapy. However, several proofs of concept reported data with murine tumor models that might have limitations for clinical translation. Magnetite is nowadays the most popular nanomaterial, but doping with distinct ions can enhance thermal therapy, namely, magnetic nanoparticle hyperthermia (MNH) and photothermal therapy (PTT). In this study, we used a 3D alveolar reconstructed A549 lung cancer tissue model and investigated the thermal properties, toxicity, and impact of the thermal dose on tissue viability and inflammatory response using magnetite codoped with 40% Zn and 2% Co divalent ions. The ZnCo-doped magnetite nanoparticles are not toxic up to an NP concentration of 30 mg/mL. PTT showed a better heat generation response than MNH under the evaluated conditions, while NP showed a high external photothermal conversion efficiency of ∼1.3 g·L^-1·cm^-1 at 808 nm. PTT study is carried out at different temperatures, 43 and 47 °C, for 15 min. Tissue viability decreased with increasing thermal dose, while intracelullar ROS levels increased, mitochondrial activity decreased, and active caspase-3 increased, suggesting cell death via apoptosis. Nanoparticles and PTT did not influence the cytokine TNF, IL-10, IL-1B, and IL-12p70. In contrast, IL-6 and IL-8 were triggered by NP and PTT. Increased expression of IL-6 and IL-8 with higher thermal doses is correlated with tissue injury results, suggesting the potential role in activating and attracting immune cells to the site of thermal-mediated tissue injury.

Development of radiosensitizers with high-energy deposition efficiency, electron transfer, and oxidative stress amplification will help to improve the efficiency of radiotherapy. To overcome the drawbacks of radiotherapy alone, it is also crucial to design a multifunctional radiosensitizer that simultaneously realizes multimodal treatment and tumor microenvironment modulation. Herein, a multifunctional radiosensitizer based on the Cu₃BiS₃-BP@PEI nanoheterostructure (NHS) for multimodal cancer treatment is designed. Cu₃BiS₃-BP@PEI NHS is able to deposit a high radiation dose into cancer cells, enhancing the radiotherapy effect. Due to the heterostructure and the synergistic effect of Cu₃BiS₃ and black phosphorus (BP), significantly boosted ¹O₂ and •OH generation is obtained under X-ray irradiation, which is promising for extremely efficient radiodynamic therapy. More importantly, the acidic tumor microenvironment (TME) can induce the cycle conversion of Cu²⁺ to Cu⁺, oxidizing glutathione (GSH) and catalyzing intracellular overproduction of H₂O₂ into highly toxic •OH, which thus further enhances reactive oxygen species (ROS) production and reduces GSH-associated radioresistance. Furthermore, Cu₃BiS₃-BP@PEI NHS has an excellent photothermal effect and can effectively transform light into heat. The outcomes of the in vitro and in vivo research confirm that the as-prepared Cu₃BiS₃-BP@PEI NHS has a high synergistic therapeutic efficacy at a low radiation dose. This work provides a viable approach to constructing a multifunctional radiosensitizer for deep tumor treatment with TME-triggered multiple synergistic therapies.

The structure of many native tissues consists of aligned collagen (Col) fibrils, some of which are further composited with dispersed hydroxyapatite (HAp) nanocrystals. Accurately mimicking this inherent structure is a promising approach to enhance scaffold biocompatibility in tissue engineering. In this study, biomimetic sheets composed of highly aligned Col fibrils were fabricated using a plastic compression and tension method, followed by the deposition of HAp nanocrystals on the surface via an alternate soaking method. The fabricated Col sheets exhibited high solid density, retained the native periodicity (D-band) of Col fibrils, and displayed plate-like HAp nanocrystals dispersed on their surface. In vitro experiments demonstrated that these sheets could regulate fibroblasts adhesion, inducing more elongated nuclei and oriented actin bundles on the aligned Col sheets. Analysis of focal adhesion assembly revealed greater cell focal adhesions on the aligned composite sheets compared to those with random Col fibril structures. Fibroblasts cultured on aligned Col with partly HAp-mineralized sheets exhibited the highest cell-extracellular matrix (ECM) protein secretion, highlighting that HAp incorporation and fibroblast alignment synergistically promote early ECM formation and wound healing. These results suggest that highly aligned Col fibrils with dispersed HAp nanocrystals, closely mimicking the microarchitecture of natural tissues, have significant potential to control cell adhesion and protein secretion for tissue engineering applications.

Oral ulcer wounds are difficult to heal due to bacterial infections, persistent inflammatory responses, and excessive reactive oxygen species (ROS). Therefore, the elimination of bacteria, removal of ROS, and reduction of inflammation are prerequisites for the treatment of mouth ulcer wounds. In this study, oligomeric proanthocyanidins (OPC) and 3-(aminomethyl)phenylboronic acid-modified hyaluronic acid (HP) were used to form polymer gels through dynamic covalent borate bonds. Minocycline hydrochloride (MH) was then loaded into the polymer gel, and a multifunctional MH/OPC-HP microneedles (MNs) with ROS-responsive properties was prepared using a vacuum method. The MH/OPC-HP MNs can rapidly release MH in a diffusive manner and sustainably release OPC in response to ROS. The gel-based MH/OPC-HP MNs extended the retention of OPC in oral ulcers, leading to prolonged ROS scavenging effects. Cytocompatibility and hemocompatibility tests showed that MH/OPC-HP MNs had good biocompatibility. Antibacterial experiments demonstrated that MNs loaded with MH exhibited excellent antibacterial effects. In vitro experiments indicated that MH/OPC-HP MNs could effectively clear ROS, reduce oxidative stress damage, inhibit M1-type macrophage polarization, and induce M2-type polarization. Furthermore, in vivo experiments revealed that MH/OPC-HP MNs could inhibit pro-inflammatory cytokines, promote neovascularization, accelerate epithelial healing of ulcers, and significantly promote healing in a rat model of oral ulcer wound infection. In summary, MH/OPC-HP MNs hold promise as a therapeutic strategy for enhancing the healing of oral ulcer wounds.

Photothermal therapy (PTT) has shown promise in the ablation of small, unresectable tumors by boosting the tumor's temperature above 50 °C. However, the high local temperature-induced cancer cell necrosis could create severe local inflammation, which may deteriorate normal tissues and increase tumor spreading. Although mild photothermal therapy (MPTT) at 42-45 °C could avoid the undesired side effect to some extent with minimal nonspecific heat diffusion, the self-protective behavior of tumors during MPTT results in an unsatisfactory therapeutic effect. Inspired by the widespread applications of traditional Chinese medicine (TCM) in various ailments, we also extensively explored the use of TCM in PTT and MPTT. In this Review, we summarize the application and function of TCM in PTT and MPTT, including the following: (1) TCM improves the performance of PTT and MPTT by elevating the photothermal conversion ability of photothermal agents (PTAs) and overcoming the self-protective effect of tumors, (2) PTT enhances TCM-based chemotherapy by improving the sensitivity and cellular uptake of TCM in tumors, and (3) natural TCM and metal-chelated TCM-based nanoparticles could directly act as PTAs for carrier-free combination therapy. We expect this Review will further illuminate TCM's utility and applicability in cancer treatment and create new combination strategies for theragnostic use.