Journal of Materials Chemistry B最新文献

Injectable hydrogels have attracted significant interest in the biomedical field due to their minimal invasiveness and accommodation of intricate scenes. Herein, we developed an injectable polyurethane-based thermogel platform by modulating the hydrophilic–hydrophobic balance of the segmented components with pendant PEG. The thermogelling behavior is achieved by a combination of the bridging from the hydrophilic PEG and the percolated network from the hydrophobic micelle core. Firstly, the thermogelation mechanism of this system was demonstrated by both DPD simulation and experimental investigation. The gelling temperature could be modulated by varying the solid content, the component of soft segments, and the length of the pendant PEG. We further applied 3D printing technology to prepare personalized hydrogel structures. This integration highlights the adaptability of our thermogel for fabricating complex and patient-specific constructs, presenting a significant advance in the field of regenerative medicine and tissue engineering. Subsequently, in vitro cell experiments demonstrated that the thermogel had good cell compatibility and could promote the proliferation and migration of L929 cells. Impressively, A549 cells could be expediently in situ parceled in the thermogel for three-dimensional cultivation and gain lifeful 3D cell spheres after 7 days. Further, in vivo experiments demonstrated that the thermogel could promote wound healing with the regeneration of capillaries and hair follicles. Ultimately, our study demonstrates the potential of hydrogels to prepare personalized hydrogel structures via 3D printing technology, offering innovative solutions for complex biomedical applications. This work not only provides a fresh perspective for the design of injectable thermogels but also offers a promising avenue to develop thermoresponsive waterborne polyurethane for various medical applications.

The skin, serving as the body's outermost layer, boasts a vast area and intricate structure, functioning as the primary barrier against external threats. Disruptions in the composition and functionality of the skin can lead to a diverse array of skin conditions, such as wounds, burns, and diabetic ulcers, along with inflammatory disorders, infections, and various types of skin cancer. These disorders not only exacerbate concerns regarding skin health and beauty but also have a significant impact on mental well-being. Due to the complexity of these disorders, conventional treatments often prove insufficient, necessitating the exploration of new therapeutic approaches. Researchers develop new therapies by deciphering these intricacies and gaining a thorough understanding of the protein networks and molecular processes in skin. A new window of opportunity has opened up for improving wound healing processes because of recent advancements in skin gene therapy. To enhance skin regeneration and healing, this extensive review investigates the use of novel dressing scaffolds in conjunction with gene therapy approaches. Scaffolds that do double duty as wound protectors and vectors for therapeutic gene delivery are being developed using innovative biomaterials. To improve cellular responses and speed healing, these state-of-the-art scaffolds allow for the targeted delivery and sustained release of genetic material. The most recent developments in gene therapy techniques include RNA interference, CRISPR-based gene editing, and the utilization of viral and non-viral vectors in conjunction with scaffolds, which were reviewed here to overcome skin disorders and wound complications. In the future, there will be rare chances to develop custom methods for skin health care thanks to the combination of modern technology and collaboration among disciplines.

Immunotherapy is an important approach in cancer treatment. Transdermal administration is emerging as a promising method for delivering immunotherapeutics. Dissolving microneedles are made mainly of soluble or biodegradable polymers and have garnered widespread attention due to their painlessness, safety, convenience, excellent drug loading capacity, and easy availability of various materials, making them an ideal transdermal delivery system. This review comprehensively summarized the preparation methods, materials, and applications of dissolving microneedles in cancer vaccines, immune checkpoint inhibitors, and adoptive cell therapy. Additionally, the challenges and perspectives associated with their future clinical translation are discussed.

Despite enormous advancements in its management, cancer is the world's primary cause of mortality. Therefore, tremendous strides were made to produce intelligent theranostics with mitigated side effects and improved specificity and efficiency. Thus, we developed a pH-sensitive theranostic platform composed of dextran immobilized zinc oxide nanoparticles, loaded with doxorubicin and radiolabeled with the technetium-99m radionuclide (^99mTc-labelled DOX-loaded ZnO@dextran). The platform measured 11.5 nm in diameter with −12 mV zeta potential, 88% DOX loading efficiency and 98.5% radiolabeling efficiency. It showed DOX release in a pH-responsive manner, releasing 93.1% cumulatively at pH 5 but just 7% at pH 7.4. It showed improved intracellular uptake, which resulted in a high growth suppressive effect against MCF-7 cancer cells as compared to the free DOX. It boasted a 4 times lower IC₅₀ than DOX, indicating its significant anti-proliferative potential (0.14 and 0.55 μg ml⁻¹, respectively). The in vitro biological evaluation revealed that its molecular mode of anti-proliferative action included downregulating Cdk-2, which provoked G1/S cell cycle arrest, and upregulating both the intracellular ROS level and caspase-3, which induced apoptosis and necrosis. The in vivo experiments in Ehrlich-ascites carcinoma bearing mice demonstrated that DOX-loaded ZnO@dextran showed a considerable 4-fold increase in anti-tumor efficacy compared to DOX. Moreover, by utilizing the diagnostic radionuclide (^99mTc), the radiolabeled platform (^99mTc-labelled DOX-loaded ZnO@dextran) was in vivo monitored in tumor-bearing mice, revealing high tumor accumulation (14% ID g⁻¹ at 1 h p.i.) and reduced uptake in non-target organs with a 17.5 T/NT ratio at 1 h p.i. Hence, ^99mTc-labelled DOX-loaded ZnO@dextran could be recommended as a rectified tumor-targeted theranostic platform.

Typically occurring after trauma or neurosurgery treatments, dura mater defect and the ensuing cerebrospinal fluid (CSF) leakage could lead to a number of serious complications and even patient's death. Although numerous natural and synthetic dura mater substitutes have been reported, none of them have been able to fulfill the essential properties, such as anti-adhesion, leakage blockage, and pro-dura rebuilding. In this study, we devised and prepared a series of robust and biodegradable hydroxyapatite/poly(lactide-co-ε-caprolactone) (nHA/PLCL) membranes for dura repair via an electrospinning technique. In particular, PLLA/PCL (80/20) was selected for electrospinning due to its mechanical properties that most closely resembled natural dural tissue. Studies by SEM, XRD, water contact angle and in vitro degradation showed that the introduction of nHA would destroy PLCL's crystalline structure, which would further affect the mechanical properties of the nHA/PLCL membranes. When the amount of nHA added increased, so did the wettability and in vitro degradation rate, which accelerated the release of nHA. In addition, the high biocompatibility of nHA/PLCL membranes was demonstrated by in vitro cytotoxicity data. The in vivo rabbit dura repair model results showed that nHA/PLCL membranes provided a strong physical barrier to stop tissue adhesion at dura defects. Meanwhile, the nHA/PLCL and commercial group's CSF had a significantly lower number of inflammatory cells than the control groups, validating the nHA/PLCL's ability to effectively lower the risk of intracranial infection. Findings from H&E and Masson-trichrome staining verified that the nHA/PLCL electrospun membrane was more favorable for fostering dural defect repair and skull regeneration. Moreover, the relative molecular weight of PLCL declined dramatically after 3 months of implantation, according to the results of the in vivo degradation test, but it retained the fiber network structure and promoted tissue growth, demonstrating the good stability of the nHA/PLCL membranes. Collectively, the nHA/PLCL electrospun membrane presents itself as a viable option for dura repair.

Designing artificial nano-enzymes for scavenging reactive oxygen species (ROS) in chondrocytes (CHOs) is considered the most feasible pathway for the treatment of osteoarthritis (OA). However, the accumulation of ROS due to the amount of nano-enzymatic catalytic site exposure and insufficient oxygen supply seriously threatens the clinical application of this therapy. Although metal–organic framework (MOF) immobilization of artificial nano-enzymes to enhance active site exposure has been extensively studied, artificial nano-enzymes/MOFs for ROS scavenging in OA treatment are still lacking. In this study, a biocompatible lubricating hydrogel-loaded iron-doped zeolitic imidazolate framework-8 (Fe/ZIF-8/Gel) centrase was engineered to scavenge endogenous overexpressed ROS synergistically generating dissolved oxygen and enhancing sustained lubrication for CHOs as a ternary artificial nano-enzyme. This property enabled the nano-enzymatic hydrogels to mitigate OA hypoxia and inhibit oxidative stress damage successfully. Ternary strategy-based therapies show excellent cartilage repair in vivo. The experimental results suggest that nano-enzyme-enhanced lubricating hydrogels are a potentially effective OA treatment and a novel strategy.

Injectable hydrogels have emerged as intelligent and versatile materials that have been proven to possess huge potential for many biomedical applications including drug delivery, tissue engineering, and regenerative medicine. Hydrogels are a class of polymers with highly hydrated 3D networks that have microenvironmental properties such as oxygen/nutrient permeability that are similar to the native extracellular matrix. In addition to possessing the typical advantages of conventional hydrogels, injectable hydrogels offer extra unique features, enabling minimally invasive injectability and durability for irregularly shaped sites, and the possibility of processing these materials via, e.g., additive manufacturing techniques. As such, there has been a growing interest in using injectable hydrogels as scaffolds/carriers for therapeutic agents, including but not limited to drugs, cells, proteins, and bioactive molecules, targeted to treat chronic diseases including cancer, but also to facilitate the repair and regeneration of damaged organs/tissues. In this themed collection of Journal of Materials Chemistry B and Biomaterials Science, we include outstanding contributions covering recent developments in this rapidly evolving field of injectable hydrogels including emerging chemistries, synthesis pathways, fabrication methods, cell–material interaction, in vitro, ex vivo and in vivo performances, and subsequent targeted applications (drug delivery, tissue engineering and regenerative medicine) of injectable hydrogels.

Doxorubicin (DOX), a chemotherapy drug, has demonstrated limited efficacy against glioblastoma, an aggressive brain tumor with resistance attributed to the blood–brain barrier (BBB). This study aims to overcome this challenge by proposing the targeted delivery of magnetic Janus nanoparticles (MJNPs) functionalized with folic acid ligands, fluorescent dye, and doxorubicin (DOX/MJNPs-FLA). The properties of these nanoparticles were comprehensively evaluated using bio-physiochemical techniques such as Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta potential analysis, high-resolution transmission electron microscopy (HR-TEM), vibrating sample magnetometry (VSM), fluorescence microscopy, MTT assay, hemolysis assay, and liver enzyme level evaluation. Dual-controlled DOX release was investigated under different pH and temperature conditions. Additionally, the impact of DOX/MJNPs-FLA on apoptosis induction in tumor cells, body weight, and survival time of cancerous animals was assessed. The targeted delivery system was assessed using C6 and OLN-93 cell lines as representatives of cancerous and healthy cell lines, respectively, alongside Wistar rat tumor-bearing models. Results from Prussian blue staining and confocal microscopy tests demonstrated the effective targeted internalization of MJNPs-FLA by glioblastoma cells. Additionally, we investigated the biodistribution of the nanoparticles utilizing fluorescence imaging techniques. This enabled us to track the distribution pattern of MJNPs-FLA in vivo, shedding light on their movement and accumulation within the biological system. Furthermore, the combination of chemotherapy and magnetic hyperthermia exhibited enhanced efficacy in inducing apoptosis, as evidenced by the increase of the pro-apoptotic Bax gene and a decrease in the anti-apoptotic Bcl-2 gene. Remarkably, this combination treatment did not cause any hepatotoxicity. This study highlights the potential of DOX/MJNPs-FLA as carriers for therapeutic and diagnostic agents in the context of theranostic applications for the treatment of brain malignancies. Additionally, it demonstrates the promising performance of DOX/MJNPs-FLA in combination treatment through passive and active targeting.

Periodontitis is an immune-inflammatory disease caused by dental plaque, and deteriorates the periodontal ligament, causes alveolar bone loss, and may lead to tooth loss. To treat periodontitis, antibacterial and anti-inflammation approaches are required to reduce bone loss. Thus, appropriate drug administration methods are significant. Due to their “syringeability”, biocompatibility, and convenience, injectable hydrogels and associated methods have been extensively studied and used for periodontitis therapy. Such hydrogels are made from natural and synthetic polymer materials using physical and/or chemical cross-linking approaches. Interestingly, some injectable hydrogels are stimuli-responsive hydrogels, which respond to the local microenvironment and form hydrogels that release drugs. Therefore, as injectable hydrogels are different and highly varied, we systematically reviewed the periodontal treatment field from three perspectives: raw material sources, cross-linking methods, and stimuli-responsive methods. We then discussed current challenges and opportunities for the translation of hydrogels to clinic, which may guide further injectable hydrogel designs for periodontitis.

Voice prostheses are known to fail in few weeks to several months of implantation due to the clogging mainly caused by microbial biofilm formation, which is a cause of concern. Iodine is a known broad-spectrum biocide and is reported to easily form complexes with various polymers. For long term device disinfection, strong iodine complexation that offers sustained iodine release for a prolonged period is essential. The present research work deals with the synthesis of a poly(methyl methacrylate-n-butyl acrylate-N-vinyl-2-pyrrolidone) (poly[MMA-BA-NVP]) tercopolymer through free radical polymerization for surface coating thermoplastic polyurethane (TPU) based voice prostheses. The NVP content in the tercopolymer was varied from 20% to 50% to optimise iodine loading and subsequent release. Base TPU coated with the tercopolymer was treated with 4% aqueous iodine solution at room temperature (28 ± 3 °C) for two hours. It was observed that the tercopolymer containing 35% N-vinyl-2-pyrrolidone (NVP), 32.5% methyl methacrylate (MMA) and 32.5% butyl acrylate (nBA) gave a stable coating on TPUs together with sustained iodine release for a prolonged period. Furthermore, the tercopolymer coated and iodine loaded TPUs exhibited excellent antimicrobial activity against Candida albicans, Staphylococcus aureus and Escherichia coli.