Biomaterials Science最新文献

Polypropylene (PP) mesh is a widely used prosthetic material in hernia repair due to its excellent mechanical properties and appropriate biocompatibility. However, its application is limited due to severe adhesion between the mesh and the abdominal viscera, leading to complications such as chronic pain, intestinal obstruction, and hernia recurrence. Currently, building anti-adhesive PP mesh remains a formidable challenge. In this work, a novel anti-adhesive PP mesh (PPM/GelMA/TA) was designed with a simple and efficient in situ gel of GelMA solution on the surface of PP mesh and further crosslinking of tannic acid (TA). It was demonstrated that PPM/GelMA/TA has good biocompatibility and excellent antioxidant property and effectively activates the polarization of macrophages toward the M2 phenotype in vitro. In addition, PPM/GelMA/TA could inhibit the growth of bacteria, which is of great significance for preventing postoperative infections. Furthermore, in the repair of full-thickness abdominal wall defects in rats, PPM/GelMA/TA reduced inflammation, promoted macrophage M2 polarization, and collagen deposition and angiogenesis so that does not cause any abdominal adhesion compared with PP mesh. As a result, our PPM/GelMA/TA shows an attractive prospect in the treatment of abdominal wall defect without adhesions.

Tumors pose a serious threat to people's lives and health, and the complex tumor microenvironment is the biggest obstacle to their treatment. In contrast to the basic protein matrices typically employed in 2D or 3D cell culture systems, decellularized extracellular matrix (dECM) can create complex microenvironments. In this study, a combination of physicochemical methods was established to obtain liver decellularized extracellular matrix scaffolds (dLECMs) to provide mechanical support and cell adhesion sites. By co-culturing tumor cells, tumor-associated stromal cells and immune cells, an in vitro 3D tumor model with a biomimetic immune microenvironment was constructed. By utilizing microenvironment data obtained from human liver tumor tissues and refining the double seeding modeling process, 3D in vitro liver tumor-like tissues with a tumor immune microenvironment (TIME) were obtained and designated as reconstructed human liver cancer (RHLC). These tissues demonstrated similar tumor characteristics and exhibited satisfactory physiological functionality. The results of metabolic characterisation and mouse tumorigenicity testing verified that the constructed RHLC significantly increased in vitro drug resistance while also closely mimicking in vivo tissue metabolism. This opens up new possibilities for creating effective in vitro models for screening chemotherapy drugs.

Immune-mediated glomerular diseases lead to chronic kidney disease (CKD), primarily through mechanisms such as immune cell overactivation, mitochondrial dysfunction and imbalance of reactive oxygen species (ROS). We have developed an ultra-small nanodrug composed of Mn₃O₄ nanoparticles which is functionalized with biocompatible ligand citrate (C-Mn₃O₄ NPs) to maintain cellular redox balance in an animal model of oxidative injury. Furthermore, this ultra-small nanodrug, loaded with tacrolimus (Tac), regulated the activity of immune cells. We established a doxorubicin (DOX)-induced CKD model in SD rats using conditions of oxidative distress. The results demonstrate the ROS scavenging capability of Mn₃O₄ NPs, which mimics enzymatic activity, and the immunosuppressive effect of tacrolimus. This combination promotes targeted accumulation in the renal region with sustained drug release through the enhanced permeability and retention (EPR) effect. Tac@C-Mn₃O₄ protects the structural and functional integrity of mitochondria from oxidative damage while eliminating excess ROS to maintain cellular redox homeostasis, thereby suppressing the overexpression of pro-inflammatory cytokines to restore kidney function and preserve a normal kidney structure, reducing inflammation and regulating antioxidant stress pathways. This dual-pronged treatment strategy also provides novel strategies for CKD management and demonstrates substantial potential for clinical translational application.

Natural small-molecule drugs have been used for thousands of years for the prevention and treatment of human diseases. Most of the natural products available on the market have been modified into various polymer materials for improving the solubility, stability, and targeted delivery of drugs. However, these nanomedicines formed based on polymer carriers would produce severe problems such as systemic toxicity and kidney metabolic stress. In contrast, the carrier-free nanomedicines formed by their self-assembly in water have inherent advantages such as low toxicity, good biocompatibility, and biodegradability. This review summarizes the assembly process and application of natural small-molecule products, which are mainly driven by multiple non-covalent interactions, and includes single-molecule assembly, bimolecular assembly, drug-modified assembly, and organogels. Meanwhile, the molecular mechanism involved in different self-assembly processes is also discussed. Self-assembly simulation and structural modification of natural small-molecule products or traditional Chinese medicine molecules using molecular dynamics simulation and computer-assisted methods are proposed, which will lead to the discovery of more carrier-free nanomedicine drug delivery systems. Overall, this review provides an important understanding and strategy to study single-molecule and multi-molecule carrier-free nanomedicines.

Early diagnosis of liver cancer and appropriate treatment options are critical for obtaining a good prognosis. However, due to technical limitations, it is difficult to make an early and accurate diagnosis of liver cancer, and the traditional imaging model is relatively simple. Therefore, we synthesized multifunctional diagnostic/therapeutic nanoparticles, UMFNPs/Ce6@MBs, loaded with ultra-small manganese ferrite nanoparticles (UMFNPs) and chlorin e6 (Ce6). This nanoplatform can take full advantage of hypoxia, acidic pH (acidosis) and increased levels of reactive oxygen species (e.g. H₂O₂) in the tumor microenvironment (TME). Specific imaging and drug release can also enhance tumor therapy by modulating the hypoxic state of the TME to achieve the combined effect of sonodynamic therapy and photodynamic therapy (SPDT). In addition, the prepared UMFNPs/Ce6@MBs have H₂O₂ and pH-sensitive biodegradability and can release UMFNPs and photosensitizer Ce6 in the TME while producing O₂ and Mn²⁺. The obtained Mn²⁺ ion nanoparticles can be used for T₁ magnetic resonance imaging of tumor-bearing mice, and the released Ce6 can provide fluorescence imaging function at the same time. Because UMFNPs/Ce6@MB ultrasonic microbubbles show good ultrasonic imaging results, UMFNPs/Ce6@MBs can simultaneously provide multi-modal imaging functions for magnetic resonance imaging (MRI), ultrasound and fluorescence imaging. In conclusion, UMFNPs/Ce6@MBs realize the synergistic treatment of SDT and PDT under multi-mode near-infrared fluorescence imaging and CEUS monitoring, demonstrating its great potential in tumor precision medicine.

The intricate nature of the tumor microenvironment (TME) results in the inefficient delivery of anticancer drugs within tumor tissues, significantly compromising the therapeutic effect of cancer treatment. To address this issue, transdermal drug delivery microneedles (MNs) with high mechanical strength have emerged. Such MNs penetrate the skin barrier, enabling efficient drug delivery to tumor tissues. This approach enhances drug bioavailability, while also mitigating concerns such as liver and kidney toxicity associated with intravenous and oral drug administration. Notably, stimulus responsive MNs designed for drug delivery have the capacity to respond to various biological signals and pathological changes. This adaptability enables them to exert therapeutic effects within the TME, exploiting biochemical variations and tailoring treatment strategies to suit tumor characteristics. The present review surveys recent advancements in responsive MN systems. This comprehensive analysis serves as a valuable reference for the prospective application of smart MN drug delivery systems in cancer therapy.

Accurate tumor localization is crucial for the success of minimally invasive surgery, as it minimizes the resection of normal tissues surrounding tumors. Traditional methods for marking gastrointestinal (GI) tumors, such as ink tattooing, intraoperative gastroscopy or colonoscopy, and placement of metal clips, have major drawbacks in their application in laparoscopic surgery. Therefore, the development of safe and easy-to-operate marking methods for accurate and real-time detection of GI tumors during laparoscopic surgery remains an ongoing challenge. Here, we propose a new fluorescent metal clip (MicBall800 clip) for noninvasive and precise fluorescence marking of GI tumors. First, we prepared a poly(methyl methacrylate) microball with small, multiple, and separated pores in its internal structure, and near-infrared fluorescence dye (IRDye800CW) and human serum albumin complex were loaded into the pores. This near-infrared-dye-loaded poly(methyl methacrylate) microball (MicBall800) was then coated onto the surface of the metal clips to produce a highly fluorescent MicBall800 clip. Safety and biocompatibility tests of the MicBall800 clip were conducted by the Korea Testing Certification Institute. The MicBall800 clip was evaluated in vivo using a porcine model. The MicBall800 clip passed safety and biocompatibility tests. The MicBall800 clip could be easily marked at the target sites without causing any side effects and was detected in real time during the laparoscopic operation. The data obtained from the safety and biocompatibility tests and the in vivo animal study indicate that the MicBall800 clip can be an important advancement in minimally invasive and precision surgery for GI cancers.

Magnetic nanoparticles (MNPs) are well-known contrast agents for use in medical imageology, facilitating disease detection via magnetic resonance imaging (MRI). With the development of nanotechnology, various MNPs have been exploited with strong contrast enhancement effects as well as multiple functions to conquer challenges related to the low detection accuracy and sensitivity. In this review, the typical characteristics and types of MNPs are outlined, and the design and fabrication of MNP-based MRI contrast agents as well as multi-mode imaging agents are also introduced by discussing the representative studies. In the pursuit of performance-enhanced MNPs, novel MNPs are expected to be developed as the next generation of contrast agents for precise bioimaging applications in a broad spectrum of fields.

Advances in nanotechnology offer promising strategies to overcome the limitations of single-drug therapies in hepatocellular carcinoma (HCC) and other cancers such as multidrug resistance and variable drug tolerances. This study proposes a targeted nanoparticle system based on a poly(β-aminoester) (PβAE) core and a hyaluronic acid (HA) shell, designed for the codelivery of doxorubicin (DOX) and indocyanine green (ICG) to effectively treat HCC. These nanoparticles demonstrated remarkable physicochemical and colloidal stability, pH- and temperature-responsive release, enhanced cellular uptake, and drug retention within tumors. Upon near-infrared (NIR) irradiation, the photothermal conversion of ICG elevated local tumor temperatures up to 53.6 °C, enhancing apoptotic cell death significantly compared to chemotherapy alone (p < 0.05). Furthermore, the dual delivery system significantly enhanced therapeutic efficacy, as evidenced by a marked decrease in tumor growth in vivo compared to controls (p < 0.01). These findings illustrate that the HA/PβAE/DOX/ICG nanoparticles are not only able to precisely target tumor cells but also overcome the limitations associated with traditional chemotherapies and photothermal treatments, suggesting a promising avenue for clinical translation of cancer therapy.

Otitis media is a prevalent pediatric condition. Local delivery of antimicrobial agents to treat otitis media is hindered by the low permeability of the stratum corneum layer in the tympanic membrane. While nanozymes, often inorganic nanoparticles, have been developed to cure otitis media in an antibiotic-free manner in a chinchilla animal model, the tympanic membrane creates an impenetrable barrier that prevents the local and non-invasive delivery of nanozymes. Here, we use a newly developed vanadium pentoxide (V₂O₅) nanowire as an example, which catalyzes the metabolic products of an otitis media pathogen (Streptococcus pneumoniae) into antiseptics, to explore the transtympanic delivery strategies for antimicrobial nanozymes. V₂O₅ nanowires with smaller dimensions (<300 nm in length) were synthesized by optimizing the synthesis conditions. To enhance penetrations across intact tympanic membranes, the nanowire was mixed or surface-modified with a trans-tympanic peptide, TMT3. The peptide-modified nanowires were characterized for their physical properties, catalytic activities, and antimicrobial activities. The cytotoxicity profile and permeation across ex vivo tympanic membrane samples were analyzed for the mixed and surface-modified nanozyme formulations.