ACS Biomaterials Science & Engineering最新文献

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.

During the host response toward implanted biomaterials, macrophages can shift phenotypes rapidly upon changes in their microenvironment within the host tissue. Exploration of this phenomenon can benefit significantly from the development of adequate tools. Creating cell microenvironment alterations on classical hydrogel substrates presents challenges, particularly when integrating them with cell cultivation and monitoring processes. However, having the capability to dynamically manipulate the cell microenvironment on biomaterial surfaces holds significant potential. We introduce magnetically actuated hydrogels (_MadSurface) tailored to induce reversible stiffness changes on polyacrylamide hydrogel substrates with embedded magnetic microparticles in a time-controllable manner. Our investigation focused on exploring the potential of magnetic fields and _MadSurfaces in dynamically modulating macrophage behavior in a programmable manner. We achieved a consistent modulation by subjecting the _MadSurface to a pulsed magnetic field with a frequency of 0.1 Hz and a magnetic field flux density of 50 mT and analyzed exposed cells using flow cytometry and ELISA. At the single-cell level, we identified a subpopulation for which the dynamic stiffness conditions in conjunction with the pulsed magnetic field increased the expression of CD206 in M1-activated THP-1 cells, indicating a consistent shift toward the M2 anti-inflammatory phenotype on _MadSurface. At the population level, this effect was mostly hindered in the culture period utilized in this work. The _MadSurface approach advances our understanding of the interplay between magnetic field, cell microenvironment alterations, and macrophage behavior.

In recent years, silk fibroin (SF) has been incorporated with low crystallinity nanohydroxyapatite (nHA) as a scaffold for various tissue regeneration applications due to the mechanical strength of SF and osteoconductive properties of nHA. However, currently, there is a lack of understanding of the immune response toward the degradation products of SF with nHA composite after implantation. It is known that particulate fragments from the degradation of a biomaterial can trigger an immune response. As the scaffold is made of degradable materials, the degradation products may contribute to the inflammation. Therefore, in this study, the effects of the enzymatic degradation of the SF/nHA scaffold on macrophage response were investigated in comparison to the control SF scaffold. Since the degradation products of a scaffold can influence macrophage polarization, it can be hypothesized that as the SF and SF/nHA scaffolds were degraded in vitro using protease XIV solution, the degradation products can contribute to the polarization of THP-1-derived macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotype. The results demonstrated that the initial (day 1) degradation products of the SF/nHA scaffold elicited a pro-inflammatory response, while the latter (day 24) degradation products of the SF/nHA scaffold elicited an anti-inflammatory response. Moreover, the degradation products from the SF scaffold elicited a higher anti-inflammatory response due to the faster degradation of the SF scaffold and a higher amino acid concentration in the degradation solution. Hence, this paper can help elucidate the contributory effects of the degradation products of SF and SF/nHA scaffolds on macrophage response and provide greater insights into designing silk-based biomaterials with tunable degradation rates that can modulate macrophage response for future tissue regeneration applications.

The demand for small-diameter vascular grafts has been globally increased but still lacks optimal solutions in this category. This study evaluated the feasibility of utilizing human pretreated fresh and nondecellularized umbilical cord arteries (hUCAs) as vascular grafts without needing any immunosuppression process. A mixed lymphocyte reaction assay revealed that hUCAs did not induce lymphocyte proliferation or cytokine production. To assess the in vivo inflammatory response, hUCAs were buried in fatty tissue under the skin of the abdominal wall in the left and right iliac fossas of rats. The average sizes of the implanted hUCAs remained consistent at 30 days post implantation. To evaluate xenogeneic transplantation, hUCAs were grafted to the abdominal aorta below the kidney of Wister rats. Remarkably, all rats exhibited positive revascularization and perfusion, maintaining blood pressure values of around 110/70 mmHg. Doppler ultrasound consistently indicated good circulation, with the three separate echogenic layers corresponding to the three arterial wall layers throughout the assessment period. Grafted rats exhibited normal motor behavior, accompanied by positive responses to thermal and pain stimulation. Blood biochemical values and whole blood cell counts showed no significant differences between pre and post-transplantation. Histological analysis of the grafts revealed no calcification or thrombosis, and a mild chronic inflammatory response was presented. In conclusion, hUCAs maintained their structural and functional properties after transplantation in rats without immunosuppression. This highlights their potential as a source for allogeneic, readily accessible, small-diameter vascular grafts.

In addition to transmitting and carrying genetic information, RNA plays an important abiotic role in the world of nanomaterials. RNA is a natural polyanionic biomacromolecule, and its ability to promote osteogenesis by binding with other inorganic materials as an osteogenic induction agent was discovered only recently. However, whether it can promote osseointegration on implants has not been reported. Here, we investigated the effect of the RNA-containing coating materials on peri-implant osseointegration. Total RNA extracted from rat muscle tissue was used as an osteogenic induction agent, and hyaluronic acid (HA) was used to maintain its negative charge. In simulated body fluids (SBF), in vitro studies demonstrated that the resulting material encouraged calcium salt deposition. Cytological experiments showed that the RNA-containing coating induced greater cell adhesion and osteogenic differentiation in comparison to the control. The results of animal experiments showed that the RNA-containing coating had osteoinductive and bone conduction activities, which are beneficial for bone formation and osseointegration. Therefore, the RNA-containing coatings are useful for the surface modification of titanium implants to promote osseointegration.

Bacterial infectious diseases remain one of the significant challenges in the field of bone regeneration applications. Despite the development of new antibiotics, their improper administration has led to the development of multiresistant bacterial strains. In this study, we proposed a novel approach to tackle this problem by loading clove oil (CLV), a natural antibacterial compound, into amino-functionalized mesoporous bioactive glass nanoparticles (MBGNs). The scanning electron microscopy images (SEM) revealed that amino-functionalization and CLV loading did not affect the shape and size of the MBGNs. The successful grafting of the amino groups on the MBGNs' surface and the presence of CLV in the material were confirmed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and zeta potential measurements. The increased CLV concentration led to a higher loading capacity, encapsulation efficiency, and antioxidant activity. The in vitro CLV release profile exhibited an initial burst release, followed by a controlled release over 14 days. The loading of CLV into MBGNs led to a stronger antibacterial effect against E. coli and S. aureus, while MG-63 osteoblast-like cell viability was enhanced with no morphological changes compared to the control group. In conclusion, the CLV-MBGNs nanocarriers showed promising properties in vitro as novel drug delivery systems, exploiting essential oils for treating bone infections and oxidative stress.

As a novel noninvasive tumor therapy, sonodynamic therapy (SDT) attracts booming concerns. However, the limited water solubility, inadequate biocompatibility, and low targeting ability of conventional sonosensitizers significantly hinder their potential for clinical application. Herein, novel zinc(II)-porphyrin nanotheranostics (HA@Zn-TCPP) were fabricated in which the zinc(II)-porphyrin (TCPP) metal-organic framework was first constructed by a simple thermal reaction, followed by the addition of hyaluronic acid (HA) for modification. The specific targeting ability of HA facilitated the internalization of HA@Zn-TCPP within tumor cells, resulting in its preferential accumulation in tumor tissues that exhibit CD44 receptor overexpression. The acidic tumor microenvironment induced the rapid decomposition of HA@Zn-TCPP, releasing free TCPP for activating SDT. This controllable generation of reactive oxygen species (ROS) could effectively decrease damage to normal tissues. The HA@Zn-TCPP exhibited remarkable antitumor effects in experiments, achieving a tumor inhibition rate of up to 82.1% when under ultrasound. This finding provides an imperative strategy to develop novel sonosensitizers for enhanced SDT.

Bacterial endophthalmitis is a severe infection of the aqueous or vitreous humor of the eye that can lead to permanent vision loss. Due to the rapid emergence of antibiotic resistance and dose-limiting toxicities, the standard treatment of bacterial endophthalmitis via the intravitreal injection of broad-spectrum antibiotics remains inadequate. Membrane active cationic antimicrobial peptides (AMPs) have emerged as a promising class of effective and broad-spectrum antimicrobial agents with potential to overcome antibiotic resistance. In this work, we investigate, for the first time, the use of omiganan (IK-12), a 12-amino acid indolicidin derivative for the treatment of bacterial endophthalmitis. Additionally, IK-12 was used as a template to perform amino acid rearrangements, without altering the length or type of amino acids, to yield a series of new derivative AMPs with varying extents of secondary structure formation under membrane mimicking conditions. IK-12 and its derivatives demonstrated strong and broad-spectrum antibacterial activities against a panel of clinically isolated Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus commonly implicated in bacterial endophthalmitis. Interestingly, two of the new IK-12 derivatives, IP-12 and WP-12, showed lower geometric mean minimum inhibitory concentration and higher 50% hemolysis concentration values, which effectively translated into 2- to 3.4-fold higher bacterial selectivity than the parent IK-12. Furthermore, the intravitreal injection of IK-12, IP-12, and WP-12 in a rabbit model of MRSA-induced endophthalmitis led to considerably improved clinical presentation and reduced recruitment of inflammatory cells. In all, these results demonstrate the potential of IK-12 and its derivatives, IP-12 and WP-12, as promising candidates for the treatment of bacterial endophthalmitis.

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.

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.