ACS Biomaterials Science & Engineering最新文献

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.

This study aimed to investigate the healing effect of a polylactic-co-glycolic acid (PLGA) scaffold containing nanohydroxyapatite (NHA) along with curcumin (CCM), loaded with adipose-derived mesenchymal stem cells (AD-MSCs), on mandibular bone defects. The designed PLGA scaffolds containing NHA were evaluated for their mechanical and structural properties. Forty rats were divided into five groups (n = 8) based on the treatment: Sham, PLGA scaffolds containing NHA, PLGA scaffolds containing NHA + CCM, PLGA scaffolds containing NHA + AD-MSCs, and PLGA scaffolds containing NHA + CCM + AD-MSCs. After 8 weeks' follow-up, mandible bones were isolated for histomorphometry evaluation. Data were analyzed using SPSS version 21, with p-values <0.05 considered statistically significant. SEM evaluation showed that the designed nanocomposite scaffold had 80% porosity. Histomorphometry results indicated a significant difference in osteocyte, osteoblast, bone area, and vascular area parameters in the group treated with scaffolds loaded with AD-MSCs + CCM compared to the other groups (p < 0.05). The PLGA-containing NHA-CCM nanocomposite scaffold demonstrated good porosity and dispersion, suitable for treating bone defects. Rats treated with scaffolds containing AD-MSCs and CCM showed better therapeutic results than the other groups. Further research is needed to evaluate its anti-inflammatory, antioxidant properties, osteogenesis, and therapeutic effects in larger animal models.

Drug solubility is a determining factor for controlled release, and solubility-dependent release kinetics can be modified by changing the drug's state in the polymer matrix through partial molecular imprinting (PMI), although research in this area remains limited. This novel PMI approach creates nanocavities within the polymer by partially retaining the imprinting molecule and trapping the drug. Such a method holds promise for developing advanced biomaterial-based drug delivery systems for anticancer therapies. In this study, we developed microspheres designed for anticancer drug delivery utilizing PMI to enhance controlled release properties. Poly(vinyl alcohol) (PVA) microspheres were partially imprinted with aspirin (ASP) to create nanocavities for gemcitabine (GEM) molecules, inducing a polymorphic shift of GEM within the polymer matrix. This novel PMI approach enhanced drug release properties by enabling control over the drug crystallinity and release rate. The PVA-ASP-GEM complex showed zero-order release kinetics, releasing 21.6% of GEM over 48 h, maintaining steady state release profile. In contrast, nonimprinted PVA-GEM microspheres exhibited first-order kinetics with a faster release of 46.85% in the same period. Quantum insights from density functional theory (DFT) calculations revealed the superior stability of the PVA-ASP-GEM complex, with a binding free energy of -56.03 kcal/mol, compared to -29.07 kcal/mol for PVA-GEM. Molecular dynamics (MD) simulations demonstrated that ASP's presence created nanocavities that restricted GEM's movement, further contributing to the controlled release. Experimental validation through differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and Raman spectroscopy confirmed the polymorphic transitions within the PVA-ASP-GEM complex. This PMI-based approach offers a promising method for modulating drug release kinetics and improving the stability of anticancer therapeutics, paving the way for innovative biomaterial-based drug delivery systems.

Dicalcium phosphate anhydrous (DCPA) presents good biomineralization ability, the strontium element is known for superior bone affinity, and a whisker possesses good mechanical strength; all these are beneficial for improving the drawbacks of hydroxyapatite (HAP) like weaker mechanical properties, poor biomineralization, and slower degradation/absorption. Therefore, a homogeneous precipitation was adopted to synthesize Sr-substituted and DCPA and HAP coexisting whiskers. The composition, structure, and morphology based on urea dosage and substitution content were characterized, and the roles of DCPA, Sr, and whisker shape were investigated. It turned out that Sr-DCPA/HAP biphasic products contained about 19% DCPA and 81% HAP, and both phases occupied the outer and inner parts of the whisker, respectively. Increasing the urea dosage made the morphology transform from a sea urchin shape to fiber clusters and then whiskers, while Sr substitution brought the whisker back to the porous microsphere shape. Only 5% of Sr content and 15 g of urea could maintain the whisker shape. Sr could promote the proliferation of MC3T3-E1 cells even at a higher extract concentration of 10 mg/mL. The cells stayed in a healthy state whether cocultured with the whisker or the microsphere. The unstable DCPA combined with the decreased crystallinity brought by Sr doping contributed to shortening the apatite deposition period to within 7 days. The whisker morphology enhanced the compressive strength of acrylic resin, and the apatite layer helped to reduce the strength loss during soaking. The Sr-DCPA/HAP biphasic whisker with enhanced overall properties possessed more promising potential for biomedical application.

Hydroxyapatite nanoparticles (nHA) have gained attention as potential intracellular drug delivery vehicles due to their high binding affinity for various biomolecules and pH-dependent solubility. Yet, the dependence of nHA cytocompatibility on their physicochemical properties remains unclear since numerous studies have revealed starkly contrasting results. These discrepancies may be attributed to differences in size, shape, crystallinity, and aggregation state of nHA, which complicates fundamental understanding of the factors driving nHA cytotoxicity. Here, we hypothesize that nHA cytotoxicity is primarily driven by intracellular calcium levels following the internalization of nHA nanoparticles. By investigating the cytotoxicity of spherical nHA with different crystallinity and dispersity, we find that both lower crystallinity and increased agglomeration of nHA raise cytotoxicity, with nanoparticle agglomeration being the more dominant factor. We show that the internalization of nHA enhances intracellular calcium levels and increases the production of reactive oxygen species (ROS). However, only subtle changes in intracellular calcium are observed, and their physiological relevance remains to be confirmed. In conclusion, we show that nHA agglomeration enhances ROS production and the associated cytotoxicity. These findings provide important guidelines for the future design of nHA-containing formulations for biomedical applications, implying that nHA crystallinity and especially agglomeration should be carefully controlled to optimize biocompatibility and therapeutic efficacy.

Mimicking the curved collagenous fibers in the cardiac extracellular matrix to fabricate elastic scaffolds in vitro is important for cardiac tissue engineering. Here, we developed sinusoidal polycaprolactone (PCL) fibrous scaffolds with commendable flexibility and elasticity to enhance the contractility of primary cardiomyocytes by employing melt-based electrohydrodynamic (EHD) printing. Microscale sinusoidal PCL fibers with an average diameter of ∼10 μm were printed to mimic the collagenous fibers in the cardiac ECM. The sinusoidal PCL fibrous scaffolds were EHD-printed in a layer-by-layer manner and exhibited outstanding flexibility and elasticity compared with the straight ones. The sinusoidal PCL scaffolds provided an elastic microenvironment for the attaching and spreading of primary cardiomyocytes, which facilitated their synchronous contractive activities. Primary cardiomyocytes also showed improved gene expression and maturation on the sinusoidal PCL scaffolds under electrical stimulation for 5 days. It is envisioned that the proposed flexible fibrous scaffold with biomimetic architecture may serve as a suitable patch for tissue regeneration and repair of damaged hearts after myocardial infarction.

Probiotics health benefits are hampered by long-term storage, gastrointestinal transit, and lack of adequate colonization within the colon. To this end, we have designed a core-shell structure that features an acid resistant core formulation with low water activity composed of alginate, hydroxypropyl methyl cellulose, and gellan gum (AHG) and a mucoadhesive shell made from chemically modified carboxymethyl chitosan with polyethylenimine (PEI-CMC). The structure of the core-shell microparticles was examined using scanning electron microscopy, and rheological measurements confirmed the improved ionic interactions between the core and the shell using the PEI-modified CMC. Simulated release from core-shell microparticles using polystyrene beads showed preferential release under intestinal conditions. PEI-CMC coating yielded improvements in mucoadhesion that was consistent with a positive shift in surface charge of the particles. Ex vivo studies using Bifidobacterium lactis probiotic bacteria demonstrated a 1.1 × 10⁵-fold improvement in bacterial viability with encapsulation under storage conditions of high humidity and temperature (30 °C). When exposed to simulated gastric fluid, encapsulation increased the probiotic viability by 3.0 × 10²-fold. In vivo studies utilizing bioluminescent Lactobacillus plantarum in mice revealed that encapsulation extended the duration of the signal within the gut and resulted in higher plate counts in suspensions isolated from the cecum. Conversely, we observed an abrupt loss of signal in the gut of the free probiotic. In conclusion, this core-shell system is suitable for improving probiotic shelf life and maximizing delivery to and retention by the colon.

Rainbow trout (Oncorhynchus mykiss) is experiencing a catastrophic pandemic. In recent years, infectious hematopoietic necrosis virus (IHNV) has spread nationwide, resulting in significant mortality. Currently, there are no available treatments or vaccines for IHNV in China. Here, the Astragalus extract was purified and characterized. Then, we developed an inactivated IHNV vaccine with purified Astragalus polysaccharide (P-APS) as an adjuvant. Safety assays showed that IHNV was successfully inactivated. After a serious IHNV challenge, the cumulative mortality rates were 76.0, 38.0, and 22.1% in control, vaccine, and P-APS + vaccine groups, respectively. P-APS + vaccine was effective at reducing head kidney damage and apoptosis after IHNV challenge by histopathological and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses. The P-APS + vaccine group showed better results in enhancing specific antibodies (IgM) and immune enzyme activities (C3, LZM, GOT, and GPT). RNA-seq revealed that many immune-related pathways were significantly enriched. TLR2, TLR7, C3, IFN-γ, IgM, MHC1, MHC2, MX1, and VIG1 were identified as core genes based on RNA-seq and PPI networks. Mechanistic investigations showed that P-APS + vaccine activates the immune pathway by upregulating the expression of these genes. P-ASP+vaccine induced effective innate and adaptive immune responses that were stronger than single vaccines after vaccination and IHNV challenged. Our findings will provide a promising vaccine candidate against IHNV.

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.

Osteoarthritis (OA) is a chronic joint disease highly associated with an imbalance in the network of inflammatory factors and typically characterized by oxidative stress and cartilage damage. Moreover, the specificity of the joint structure makes it difficult for drugs to achieve good penetration and effective enrichment in the joint cavity. Therefore, therapeutic strategies that increase the specific targeting of drugs to inflammatory joint and incorporate antioxidative stress effects are important to improve the efficacy of OA. Here, we developed a folic acid-modified liposomal nanoparticle (AST@Lip-FA) loaded with the antioxidant astaxanthin (AST) to enhance the water solubility and stability of AST and to target the delivery of AST to the site of OA, leading to a significant improvement in therapeutic efficacy. In vitro experiments demonstrated that, due to the recognition by FA of the receptor folate receptor β on the surface of activated macrophages, the cellular uptake efficiency of AST@Lip-FA was increased. Meanwhile, intracellularly overexpressed inflammatory mediators such as reactive oxygen species and nitric oxide were efficiently removed by AST@Lip-FA. In addition, in the ACLT-induced OA mouse model, AST@Lip-FA was precisely enriched in the inflamed joints and achieved long-term retention, fully utilizing the anti-inflammatory, antioxidant, and cartilage-protecting effects of AST to effectively alleviate the progression of OA. In summary, AST@Lip-FA has an important prospect as a potential and effective therapeutic strategy for OA.