ACS Biomaterials Science & Engineering最新文献

The complexation of nucleic acids and collagen forms a platform biomaterial greater than the sum of its parts. This union of biomacromolecules merges the extracellular matrix functionality of collagen with the designable bioactivity of nucleic acids, enabling advances in regenerative medicine, tissue engineering, gene delivery, and targeted therapy. This review traces the historical foundations and critical applications of DNA-collagen complexes and highlights their capabilities, demonstrating them as biocompatible, bioactive, and tunable platform materials. These complexes form structures across length scales, including nanoparticles, microfibers, and hydrogels, a process controlled by the relative amount of each component and the type of nucleic acid and collagen. The broad distribution of different types of collagen within the body contributes to the extensive biological relevance of DNA-collagen complexes. Functional nucleic acids can form these complexes, such as siRNA, antisense oligonucleotides, DNA origami nanostructures, and, in particular, single-stranded DNA aptamers, often distinguished by their rapid self-assembly at room temperature and formation without external stimuli and modifications. The simple and seamless integration of nucleic acids within collagenous matrices enhances biomimicry and targeted bioactivity, and provides stability against enzymatic degradation, positioning DNA-collagen complexes as an advanced biomaterial system for many applications including angiogenesis, bone tissue regeneration, wound healing, and more.

Effective storage and utilization of limited donor corneal resources are in high demand to alleviate the shortage of donor corneal tissue. Here, we designed a static air-lifted organ culture system equipped with a protective coverage membrane, namely, an air-lifted OC-P system, to provide a biomimetic physiological environment for full-thickness corneal preservation. The air-lifted OC-P system features a unique collagen-based protective coverage membrane that can offer a moist, oxygen-rich environment for corneal epithelium, produce an appropriate intraocular pressure onto the cornea by gravity, and facilitate the maintenance of the organ culture medium level for nutrient supply during corneal preservation. Compared with conventional submerged and air-lifted corneal preservation methods, the air-lifted OC-P system remarkably improved the overall quality of the preserved corneas. These preserved corneas not only exhibited superior controllability of corneal swelling and extraordinary maintenance of the morphology and viability of all three types of corneal cells (i.e., corneal epithelium, keratocytes, and endothelium) but also demonstrated optimal optical, thermal, and mechanical properties. This air-lifted OC-P system presents a biomimetic strategy that provides a static and efficient method to replicate the corneal natural conditions for corneal preservation effectively.

Effective storage and utilization of limited donor corneal resources are in high demand to alleviate the shortage of donor corneal tissue. Here, we designed a static air-lifted organ culture system equipped with a protective coverage membrane, namely, an air-lifted OC-P system, to provide a biomimetic physiological environment for full-thickness corneal preservation. The air-lifted OC-P system features a unique collagen-based protective coverage membrane that can offer a moist, oxygen-rich environment for corneal epithelium, produce an appropriate intraocular pressure onto the cornea by gravity, and facilitate the maintenance of the organ culture medium level for nutrient supply during corneal preservation. Compared with conventional submerged and air-lifted corneal preservation methods, the air-lifted OC-P system remarkably improved the overall quality of the preserved corneas. These preserved corneas not only exhibited superior controllability of corneal swelling and extraordinary maintenance of the morphology and viability of all three types of corneal cells (i.e., corneal epithelium, keratocytes, and endothelium) but also demonstrated optimal optical, thermal, and mechanical properties. This air-lifted OC-P system presents a biomimetic strategy that provides a static and efficient method to replicate the corneal natural conditions for corneal preservation effectively.

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.

Octacalcium phosphate (OCP) has been used as a bone replacement material due to its higher bone affinity. However, the mechanism of affinity has not been clarified. Since the 100 crystalline plane of OCP is closely involved in the biological reactions during osteogenesis, it is important to expose the 100 crystalline plane of OCP to the biological fluid to precisely measure the interfacial reactions. In this study, the OCP plate-like crystals were fixed on a conductive substrate in the form of single-particle deposition, and the thin films with exposing 100 crystalline planes were fabricated. Then, the characteristics of hydration layers in the OCP crystals were enhanced by the exposure of 100 crystalline planes through the thin film formation, and the bioreactivity was found to be associated with the swelling and dissolution of the hydration layer in the biological fluid. Specifically, the OCP crystals were deposited on the gold sensor by electrophoretic deposition (OCP/Au-1). The results showed that the OCP plate-like crystals were selectively deposited on the gold sensor by electrophoresis. Subsequently, it was found that the ultrasonication of OCP/Au-1 resulted in the formation of an OCP crystalline thin film (m-OCP/Au-1) with the single-particle thickness on the gold sensor with exposing 100 crystalline planes. Moreover, the FT-IR spectra of m-OCP/Au-1 showed that the structure of the phosphate ions was rearranged by ultrasonication in the hydration layer, resulting in the regulation of the layered nanostructures, promoting higher crystallinity. Furthermore, the XPS spectra of m-OCP/Au-1 indicated that the hydrogen phosphate ions in the hydration layer were exposed on the 100 crystalline plane of the topmost surface. The prepared m-OCP/Au-1 was stable in citrate buffer, whereas it showed very high reactivity in phosphate buffer as the hydration layer gradually dissolved after the swelling, which was measured by the QCM-D technique. Therefore, the OCP crystalline thin films in this study were found to have higher surface reactivity due to the enhanced exposure of the hydration layer, which is assumed to be the cause of their bone-regeneration-promoting effect (i.e., higher bone affinity). The films in this study were stable at gastric acid pH and dissolved at neutral pH, which could make them useful as the orally administered drug carrier.

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.

Octacalcium phosphate (OCP) has been used as a bone replacement material due to its higher bone affinity. However, the mechanism of affinity has not been clarified. Since the 100 crystalline plane of OCP is closely involved in the biological reactions during osteogenesis, it is important to expose the 100 crystalline plane of OCP to the biological fluid to precisely measure the interfacial reactions. In this study, the OCP plate-like crystals were fixed on a conductive substrate in the form of single-particle deposition, and the thin films with exposing 100 crystalline planes were fabricated. Then, the characteristics of hydration layers in the OCP crystals were enhanced by the exposure of 100 crystalline planes through the thin film formation, and the bioreactivity was found to be associated with the swelling and dissolution of the hydration layer in the biological fluid. Specifically, the OCP crystals were deposited on the gold sensor by electrophoretic deposition (OCP/Au-1). The results showed that the OCP plate-like crystals were selectively deposited on the gold sensor by electrophoresis. Subsequently, it was found that the ultrasonication of OCP/Au-1 resulted in the formation of an OCP crystalline thin film (m-OCP/Au-1) with the single-particle thickness on the gold sensor with exposing 100 crystalline planes. Moreover, the FT-IR spectra of m-OCP/Au-1 showed that the structure of the phosphate ions was rearranged by ultrasonication in the hydration layer, resulting in the regulation of the layered nanostructures, promoting higher crystallinity. Furthermore, the XPS spectra of m-OCP/Au-1 indicated that the hydrogen phosphate ions in the hydration layer were exposed on the 100 crystalline plane of the topmost surface. The prepared m-OCP/Au-1 was stable in citrate buffer, whereas it showed very high reactivity in phosphate buffer as the hydration layer gradually dissolved after the swelling, which was measured by the QCM-D technique. Therefore, the OCP crystalline thin films in this study were found to have higher surface reactivity due to the enhanced exposure of the hydration layer, which is assumed to be the cause of their bone-regeneration-promoting effect (i.e., higher bone affinity). The films in this study were stable at gastric acid pH and dissolved at neutral pH, which could make them useful as the orally administered drug carrier.

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.

In most studies, the penetration of nanoparticles into tumors was mainly dependent on the enhanced permeability and retention (ERP) effect. However, the penetration of nanoparticles would be limited by tumor-dense structure, immune system, and other factors. To solve these problems, macrophages with active tropism to tumor tissues, loaded nanoparticles with photothermal therapy, and chemotherapy were designed. In detail, liquid metal (gallium indium alloy) nanoparticles were modified with mesoporous silica and then embedded with the chemotherapeutic drug sorafenib (LM@Si/SO) for photothermal therapy and chemotherapy. After that, the LM@Si/SO nanoparticles were carried by the mouse macrophage RAW264.7 cell line (LM@Si/SO@R) to increase the accumulation of the nanoparticles in the tumor site and improve the tumor immune microenvironment. With the enhanced tumor accumulation, LM@Si/SO@R exhibited excellent antitumor ability in vitro and in vivo. Thus, these strategies via the cell carrier to enhance tumor therapeutic efficiency had the potential for the improvement of tumor therapy.

In most studies, the penetration of nanoparticles into tumors was mainly dependent on the enhanced permeability and retention (ERP) effect. However, the penetration of nanoparticles would be limited by tumor-dense structure, immune system, and other factors. To solve these problems, macrophages with active tropism to tumor tissues, loaded nanoparticles with photothermal therapy, and chemotherapy were designed. In detail, liquid metal (gallium indium alloy) nanoparticles were modified with mesoporous silica and then embedded with the chemotherapeutic drug sorafenib (LM@Si/SO) for photothermal therapy and chemotherapy. After that, the LM@Si/SO nanoparticles were carried by the mouse macrophage RAW264.7 cell line (LM@Si/SO@R) to increase the accumulation of the nanoparticles in the tumor site and improve the tumor immune microenvironment. With the enhanced tumor accumulation, LM@Si/SO@R exhibited excellent antitumor ability in vitro and in vivo. Thus, these strategies via the cell carrier to enhance tumor therapeutic efficiency had the potential for the improvement of tumor therapy.