Biomaterials Science最新文献

Gadolinium-doped ultra-small organic particles are a promising material for theranostics, particularly as contrast agents for MRI. However, a number of unresolved issues remain regarding their potential effects on organs and tissues, especially due to possible toxic effects of gadolinium ions. The aim of this work was to conduct a comprehensive study of the functional state of the digestive system after an intravenous injection of a colloidal solution of gadolinium-doped carbon dot nanohybrids (GDNHs). The study was performed on Wistar rats. Spontaneous and agonist-induced contractions of the circular smooth muscle (SM) preparations from the gastric antrum and the caecum were measured in isometric mode. Lipid fractions and free amino acids in blood plasma were determined chromatographically. Molecular docking of GDNHs to the structure of the muscarinic acetylcholine receptor was performed using blind rigid docking with Smina osx.12. It was found that intravenous administration of GDNHs generally induced changes in spontaneous SM contractile activity, including increased contraction amplitude and altered frequency, modification of contraction–relaxation cycle durations and velocities, and enhanced efficiency indices. Under these conditions, mechanisms regulating and maintaining physiologically relevant differences in the mechanokinetic parameters of SM contractions across different digestive tract regions were also altered. Moreover, GDNHs modulated the mechanisms of adrenergic inhibition and cholinergic excitation in the antrum and caecum. The effects of GDNHs on carbacholine-induced contractions of the antrum SM were mainly attributed to their organic components, whereas in the caecum, they were predominantly mediated by Gd³⁺ ions complexed with nanohybrids. Molecular docking revealed characteristic binding interactions at the interfaces between the GDNHs and the muscarinic acetylcholine receptor in a potential competition with acetylcholine molecules. In addition, changes were observed in the concentrations of most lipid fractions and certain free amino acids in rat blood plasma. Overall, intravenous administration of GDNHs was accompanied by enhanced gastrointestinal SM motility (due to the activation of cholinergic excitation) and partial modulation of hepatic lipid and protein metabolism. However, these effects did not lead to pronounced dysfunction of the digestive system, indicating that GDNHs can be considered a promising basis for the development of MRI contrast agents.

Ensuring a stable oxygen supply for transplanted cells remains a major challenge in the clinical translation of tissue engineering and regenerative medicine. Hypoxic environments caused by insufficient vascularization are a key factor leading to cell death and graft failure. To address this issue, we developed an injectable, oxygen-generating thermoresponsive hydrogel system based on poly(organophosphazene) (PPZ). By modulating the gelatin and calcium peroxide (CaO₂) content, we fabricated calcium peroxide-loaded (CPO) microspheres with distinct oxygen release profiles and incorporated them into the PPZ hydrogel, forming a hydrogel based oxygen delivery platform, termed OxyCellgel. This platform, composed solely of PPZ and CPO microspheres, allows for precise control over oxygen release rates and amounts, enabling adaptation to both mild and severe hypoxic environments. The interaction between the microspheres and hydrogel matrix facilitated uniform and sustained oxygen release. Subsequently, human mesenchymal stem cells (hMSCs) were co-delivered with this OxyCellgel system to evaluate cell viability and function under hypoxic conditions. The system significantly enhanced the survival and proliferation of hMSCs and promoted angiogenesis through their paracrine effects under hypoxia. Notably, hMSCs co-encapsulated with OxyCellgel showed markedly improved viability under hypoxic conditions compared to controls. This study presents a hydrogel-based oxygen delivery platform with controllable release kinetics as a promising strategy to improve the efficacy of stem cell-based therapies under diverse hypoxic conditions.

Cerenkov radiation-induced photodynamic therapy (CR-PDT) offers a promising approach for overcoming the dependency on external light sources and associated tissue penetration limitations. However, the therapeutic efficacy of CR-PDT is constrained by tumor hypoxia and the intrinsically short half-life and limited diffusion distance of reactive oxygen species (ROS). Herein, we propose a tumor acidity-triggered, mitochondria-targeted CR-PDT strategy to amplify ROS generation for enhanced therapeutic efficacy. The mitochondria-targeted photosensitizer (TTCPP) is encapsulated within amphiphilic polymers functionalized with an acidity-responsive moiety and a ¹³¹I labeling group, forming ¹³¹I-TTCPP nanoparticles (¹³¹I-TTCPP NPs). Under physiological conditions, ¹³¹I-TTCPP NPs exhibit minimal phototoxicity due to aggregation-caused quenching (ACQ). Upon encountering the acidic tumor microenvironment, ¹³¹I-TTCPP NPs disintegrate, restoring the photodynamic activity of TTCPP. Compared to the non-targeted photosensitizer TCPP, the released mitochondria-targeted TTCPP effectively localizes to mitochondria and undergoes self-activation by ¹³¹I, generating significantly higher levels of ROS, which results in more severe mitochondrial dysfunction and enhanced apoptosis. Our findings demonstrate that coupling mitochondrion targeting with self-activated CR-PDT provides a more effective and safer option for cancer treatment.

Mesenchymal stromal cells (MSCs) hold great promise for tissue regeneration due to their potent paracrine effects. However, the absence of extracellular matrix (ECM) support following transplantation significantly compromises their survival and therapeutic efficacy. To address this, we developed a single-cell encapsulation strategy using an ECM-mimetic supramolecular hydrogel system based on host–guest chemistry. In this approach, cholesterol–polyethylene glycol–adamantane is inserted into the MSC membrane via hydrophobic interactions, enabling the subsequent formation of a uniform hydrogel coating through specific recognition between cyclodextrin- and adamantane-modified hyaluronic acids. This facile and biocompatible strategy achieves high encapsulation efficiency without the need for complex equipment, while preserving cell viability and function. Encapsulated MSCs exhibited enhanced resistance to pathological stress, improved survival, and superior therapeutic efficacy in a rat model of myocardial infarction. These findings highlight the potential of supramolecular single-cell encapsulation to augment MSC-based therapies for tissue repair and regenerative medicine.

A noncovalent chitosan (CS)/hyaluronic acid (HA) hydrogel characterized by favorable cytocompatibility, biodegradability and non-toxicity is reported. It bears a close resemblance to human skin and holds promising potential for application in medical engineering. Nevertheless, CS/HA hydrogels have not yet achieved widespread application due to their relatively weak mechanical properties. In this study, salts were utilized to regulate the mechanical properties of a CS/HA hydrogel. The results indicated that copper nitrate was the most effective regulator, as it transformed intramolecular hydrogen bonds into intermolecular hydrogen bonds and electrostatic interactions into cation chelations, respectively. The regular domains in the hydrogel were reduced, while the crosslinking was strengthened. Consequently, the toughness of the hydrogel was increased to 7.8 MJ m^-3, 1253-fold that of the covalent CS/HA hydrogel. The salt effect was replicated in another two hydrogels, attesting to its generality. Hence, salt regulation proves to be an effective way to enhance the mechanical properties of hydrogels. In addition, the copper nitrate-regulated hydrogel exhibited favorable drug delivery behavior and photothermal response. Under near-infrared light exposure, the release rate and release amount of the loaded drug from the hydrogel increased by 40% and 39%, respectively, within 20 minutes, demonstrating its significant potential as a drug carrier.

Correction for ‘Preparation of antibacterial polypeptides with different topologies and their antibacterial properties’ by Xiaodan Wang et al., Biomater. Sci., 2022, 10, 834–845, https://doi.org/10.1039/D1BM01620B.

Cancer treatment faces significant challenges due to tumor heterogeneity, drug resistance, and the limited efficacy of single-agent therapies, driving the search for novel therapeutic approaches. The water-soluble molybdenum cluster complex Na₅Cs₃[{Mo₆I₈}(S₂O₃)₆]·3H₂O, developed in this study, represents a unique compound that combines a strong chemotherapeutic effect, achieved through the controlled release of sulfur-containing gas-signaling molecules (H₂S and SO₂) during hydrolysis, with a radiodynamic effect, enabled by the ability of the cluster to generate singlet oxygen (¹O₂) under X-rays. The results of in vitro experiments confirmed significant cytostatic effects on cancer cells, while in vivo studies using Nu/J mice xenografted with HeLa tumors showed substantial tumor growth inhibition when the cluster was administered subcutaneously in combination with X-ray irradiation. Overall, the dual functionality of the cluster, along with the slow release and prolonged retention of the complex in tumor tissues, makes it a highly promising candidate for advanced cancer treatment strategies, particularly when integrated with conventional radiotherapy.

This study developed biomimetic nanoparticles by coating poly(lactic-co-glycolic acid) (PLGA) nanoparticles with membranes derived from osteosarcoma cells, forming cell membrane-coated nanoparticles (CMCNPs). The CMCNPs showed specific binding to their source cancer cells (homotypic targeting) while evading detection by macrophages and degradation in lysosomes. The stealth property of CMCNPs was demonstrated by reduced protein adsorption and minimal liver retention in vivo. The work highlights the role of Disabled Homolog-2 (Dab2) in mediating the internalization of CMCNPs. Through mass spectrometry based label-free quantitative proteomics and inhibitor studies, this study reveals the contribution of Dab2 to enhancing the cytosolic delivery of nanoparticles. Building on this mechanistic insight, the therapeutic potential of CMCNPs was evaluated by encapsulating an siRNA payload targeting the oncogenic mRNA survivin. The release of siRNA from the nanoparticles demonstrated significant tumor penetration and regression activity, with no off-target effects observed on major organs in vivo, enabling precise survivin gene targeting with enhanced specificity and therapeutic efficacy for osteosarcoma management.

Correction for ‘Aggregation-induced emission photosensitizer microneedles for enhanced melanoma photodynamic therapy’ by Ling Liang et al., Biomater. Sci., 2024, 12, 1263–1273, https://doi.org/10.1039/D3BM01819A.

Implantable drug delivery systems (IDDS) hold great promise for sustained therapeutic administration, particularly for deep tissues like the inner ear. However, the obstruction of delivery systems induced by foreign body reactions (FBRs) remains a significant challenge to long-term implantation. Here, we developed a bio-inspired zwitterionic nanocoating (PDA-PSB) for IDDS. Experimental results showed that the PDA-PSB coating significantly improved the hydrophilicity, reduced protein and cell adhesion, and effectively suppressed inflammatory responses. To evaluate the long-term performance, we implanted PDA-PSB-coated microcatheters subcutaneously and in the tympanic bullae of rats for six months. Dynamic observations revealed that, in the uncoated group, fibrotic tissues resulting from the FBRs gradually infiltrated the lumen of the microcatheter, ultimately causing complete occlusion. In contrast, the PDA-PSB-coated microcatheters significantly reduced the fibrosis and prevented obstruction. Pressure measurements further demonstrated that the PDA-PSB-coated microcatheters maintained low drug delivery pressure after long-term implantation, ensuring sustained patency and continuous drug delivery. Mechanistic studies revealed that the PDA-PSB coating inhibited early macrophage M1 polarization and prevented macrophage transition into myofibroblasts (MMT), thereby reducing collagen deposition. This study provides a novel solution for improving the performance of IDDS and highlights its considerable potential for long-term application.