ACS Biomaterials Science & Engineering最新文献

Polylactide-polyglycolide (PLGA) is one of the most attractive polymeric biomaterials used to fabricate medical devices for drug delivery and tissue engineering applications. Nevertheless, the utilization of PLGA in load-bearing applications is restricted due to its inadequate mechanical properties. This study examines the potential of recombinant silk fibroin (eADF4), a readily producible biomaterial, as a reinforcing agent for PLGA. The PLGA/eADF4 composite membranes were developed by using the process of electrospinning. The spinnability of the electrospinning solutions and the physicochemical, mechanical, and thermal properties of the composite membranes were characterized. The addition of eADF4 increased the viscosity of the electrospinning solutions and enhanced both the mechanical characteristics and the thermal stability of the composites. This study demonstrates that PLGA membranes reinforced with recombinant spider silk fibroin are noncytotoxic, significantly enhance cell migration and wound closure, and do not trigger an inflammatory response, making them ideal candidates for advanced wound healing applications.

The tunable mechanical properties of polyurethanes (PUs), due to their extensive structural diversity and biocompatibility, have made them promising materials for biomedical applications. Scientists can address PUs' issues with platelet absorption and thrombus formation owing to their modifiable surface. In recent years, PUs have been extensively utilized in biomedical applications because of their chemical stability, biocompatibility, and minimal cytotoxicity. Moreover, addressing challenges related to degradation and recycling has led to a growing focus on the development of biobased polyurethanes as a current focal point. PUs are widely implemented in cardiovascular fields and as implantable materials for internal organs due to their favorable biocompatibility and physicochemical properties. Additionally, they show great potential in bone tissue engineering as injectable grafts or implantable scaffolds. This paper reviews the synthesis methods, physicochemical properties, and degradation pathways of PUs and summarizes recent progress in applying different types of polyurethanes in various biomedical applications, from wound repair to hip replacement. Finally, we discuss the challenges and future directions for the translation of novel polyurethane materials into biomedical applications.

One of the most dangerous aspects of cancers is their ability to metastasize, which is the leading cause of death. Hence, it holds significance to develop therapies targeting the eradication of cancer cells in parallel, inhibiting metastases in cells surviving the applied therapy. Here, we focused on two melanoma cell lines─WM35 and WM266-4─representing the less and more invasive melanomas. We investigated the mechanisms of cellular processes regulating the activation of actomyosin as an effect of colchicine treatment. Additionally, we investigated the biophysical aspects of supplement therapy using Rho-associated protein kinase (ROCK) inhibitor (Y-27632) and myosin II inhibitor ((-)-blebbistatin), focusing on the microtubules and actin filaments. We analyzed their effect on the proliferation, migration, and invasiveness of melanoma cells, supported by studies on cytoskeletal architecture using confocal fluorescence microscopy and nanomechanics using atomic force microscopy (AFM) and microconstriction channels. Our results showed that colchicine inhibits the migration of most melanoma cells, while for a small cell population, it paradoxically increases their migration and invasiveness. These changes are also accompanied by the formation of stress fibers, compensating for the loss of microtubules. Simultaneous administration of selected agents led to the inhibition of this compensatory effect. Collectively, our results highlighted that colchicine led to actomyosin activation and increased the level of cancer cell invasiveness. We emphasized that a cellular pathway of Rho-ROCK-dependent actomyosin contraction is responsible for the increased invasive potential of melanoma cells in tubulin-targeted therapy.

Progressive cartilage degradation, synovial inflammation, and joint lubrication dysfunction are key markers of osteoarthritis. The composition of synovial fluid (SF) is altered in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. Lubricin's distinct bottlebrush mucin domain has been speculated to contribute to its lubricating ability, but the relationship between its structure and mechanical function in SF is not well understood. Here, we demonstrate the application of a novel mucinase (StcE) to selectively degrade lubricin's mucin domain in SF to measure its impact on joint lubrication and friction. Notably, StcE effectively degraded the lubricating ability of SF in a dose-dependent manner starting at nanogram concentrations (1-3.2 ng/mL). Further, the highest StcE doses effectively degraded lubrication to levels on par with trypsin, suggesting that cleavage at the mucin domain of lubricin is sufficient to completely inhibit the lubrication mechanism of the collective protein component in SF. These findings demonstrate the value of mucin-specific experimental approaches to characterize the lubricating properties of SF and reveal key trends in joint lubrication that help us better understand cartilage function in lubrication-deficient joints.

Infection with drug-resistant bacteria and the formation of biofilms are the main factors contributing to wound healing insufficiency. Antibacterial agents with enzyme-like properties have exhibited considerable potential for efficient eradication of drug-resistant microorganisms due to their superior sensitivities and minimal side effects. In this work, we prepared a kind of Fe-centered single-atom nanozyme (Fe-SAzyme) with high biocompatibility and stability via a facile one-pot hydrothermal method, which was suitable for the treatment of wounds infected with drug-resistant bacteria. The Fe-SAzyme exhibited remarkable peroxidase-like catalytic activities, catalyzing the conversion of hydrogen peroxide (H₂O₂) to highly toxic hydroxyl radicals (^•OH), which could not only damage bacterial cells but also inhibit, disrupt, and eradicate the formation of bacterial biofilms. Thus, Fe-SAzyme demonstrated a broad-spectrum antibacterial performance capable of effectively eliminating multidrug-resistant bacteria. The coexistence of ferrous (Fe²⁺) and ferric (Fe³⁺) ions in Fe-SAzyme conferred the nanozyme with anti-inflammatory activity, effectively suppressing excessive inflammation. Meanwhile, Fe-SAzyme could significantly downregulate inflammatory cytokines tumor necrosis factor-α and interleukin-1β and upregulate growth factors VEGF and epidermal growth factor, which can prevent bacterial infection, mitigate inflammation, promote fibroblast proliferation, and improve wound closure. Thus, Fe-SAzyme had shown favorable therapeutic efficiency in promoting bacteria-infected wound healing. This study provides Fe-SAzyme as a promising candidate for the development of new strategies to treat multidrug-resistant bacterial infections.

Three-dimensional (3D) bioprinting technology stands out as a promising tissue manufacturing process to control the geometry precisely with cell-loaded bioinks. However, the isotropic culture environment within the bioink and the lack of topographical cues impede the formation of oriented cardiac tissue. To overcome this limitation, we present a novel method named 3D nanofiber-assisted embedded bioprinting (3D-NFEP) to fabricate cardiac tissue with an oriented morphology. Aligned 3D nanofiber scaffolds were fabricated by divergence electrospinning, which provided structural support for printing of the low-viscosity bioink and structural induction to cardiomyocytes. Cells adhered to the aligned fibers after hydrogel degradation, and a high degree of cell alignment was observed. This technology was also demonstrated as a feasible solution for multilayer cell printing. Therefore, 3D-NFEP was demonstrated as a promising method for bioprinting oriented cardiac tissue with low-viscosity bioink and is expected to be applied for structured and cardiac tissue engineering.

Complex coacervates, formed through electrostatic interactions between oppositely charged polymers, present a versatile platform for drug delivery, providing rapid assembly, selective encapsulation, and responsiveness to environmental stimuli. The architecture and properties of coacervates can be tuned by controlling structural and environmental design factors, which significantly impact the stability and delivery efficiency of the drugs. While environmental design factors such as salt, pH, and temperature play a crucial role in coacervate formation, structural design factors such as polymer concentration, polymer structure, mixing ratio, and chain length serve as the core framework that shapes coacervate architecture. These elements modulate the phase behavior and material properties of coacervates, allowing for a highly tunable system. In this review, we primarily analyze how these structural design factors contribute to the formation of diverse coacervate architecture, ranging from bulk coacervates to polyion complex micelles, vesicles, and cross-linked gels, though environmental design factors are considered. We then examine the effectiveness of these architectures in enhancing the delivery and efficacy of drugs across various administration routes, such as noninvasive (e.g., oral and transdermal) and invasive delivery. This review aims to provide foundational insights into the design of advanced drug delivery systems by examining how the origin and chemical structure of polymers influence coacervate architecture, which in turn defines their material properties. We then explore how the architecture can be tailored to optimize drug delivery for specific administration routes. This approach leverages the intrinsic properties derived from the coacervate architecture to enable targeted, controlled, and efficient drug release, ultimately enhancing therapeutic outcomes in precision medicine.

Covalent cross-linking is a common strategy to improve the mechanical properties of biological polymers. The most prominent field of application of such materials is in medicine, for example, in the form of bioprinting, drug delivery, and wound sealants. One biological polymer of particular interest is the blood clotting protein fibrinogen. In the natural process, fibrinogen polymerizes to fibrous hydrogel fibrin. Although the material shows great potential, its costs are very high due to the required enzyme thrombin. Recently, we introduced several approaches to trigger a thrombin-free fibrillogenesis of fibrinogen to a fibrin-like material. Inspired by the natural pathway of blood clotting in which covalent cross-linking stabilizes the clot, this "pseudofibrin" is now developed even further by covalently cross-linking the fibers. In particular, the effect of inexpensive glutaraldehyde on fiber morphology, rheological properties, and irreversible gel dissolution is investigated. Additionally, new insights into the reaction kinetics between fibrinogen and glutaraldehyde are gained. It could be shown that the fibrous structure of pseudofibrin can be retained during cross-linking and that glutaraldehyde significantly improves rheological properties of the hydrogels. Even more important, cross-linking with glutaraldehyde can prevent dissolution of the gels at elevated temperatures.

Photodynamic therapy (PDT) has been widely used in the clinical therapy of various tumors, especially superficial tumors. However, the tumor microenvironment presents hypoxia, as well as the inherent antioxidant system (e.g., Nrf2) of tumor cells limits the therapeutic outcomes. Herein, a cascade-responsive "oxidative stress amplifier" (named EZ@TD) is designed by encapsulating manganese-doped carbon dots acting as a photosensitizer and catalase (CAT)-like nanozyme within pH-sensitive ZIF-8 and Zn²⁺-activated DNAzyme for relieving hypoxia and efficient Nrf2 gene disruption to enhance PDT. It is demonstrated that EZ@TD synergistically inhibited tumor growth and activated the antitumor immune response by inhibiting the Nrf2/ARE signaling pathway in tumors. We provide a new paradigm for amplifying intracellular oxidative stress by interfering with various signaling pathways.

Physical stimulations such as mechanical and electric stimulation can continuously work on bone defect locations to maintain and enhance cell activity, and it has become a hotspot for research in the field of bone repair. Herein, bifunctional porous composite scaffolds with shape memory and piezoelectric functions were fabricated using thermoplastic polyurethane (TPU) and poly(vinylidene fluoride) through triply periodic minimal surfaces design and selective laser sintering technology. Thereinto, the shape fixity ratio and recovery ratio of the composite scaffold reached 98.6% and 81.2%, respectively, showing excellent shape memory functions. More importantly, its piezoelectric coefficient (d33 = 2.47 pC/N) is close to the piezoelectric constant of bone tissue (d33 = 0.7-2.3 pC/N), and the voltage released during the compression process can reach 0.5 V. Furthermore, cyclic compression experiments showed that the strength of composite scaffold was up to 8.3 times compared with the TPU scaffold. Besides, the composite scaffold showed excellent cytocompatibility. In conclusion, the composite scaffold is expected to continuously generate mechanical and electric stimulation due to shape memory and piezoelectric function, respectively, which provide an effective strategy for bone repair.