ACS Biomaterials Science & Engineering最新文献

Vertebroplasty is a minimally invasive surgical procedure used to treat vertebral fractures, which conventionally involves injecting poly(methyl methacrylate) (PMMA) bone cement into the fractured vertebra. A common risk associated with vertebroplasty is cement leaking out of the vertebra during the injection, which may occur due to a lack of understanding of the complex flow behavior. Therefore, experiments to quantify the cement's flow properties are necessary for understanding and proper handling of the bone cement. In this study, we aimed to characterize the behavior of PMMA bone cement in its curing stages to obtain parameters that govern the flow behavior during injection. We used rotational and oscillatory rheometry for our measurements, as well as a custom-made injector setup that replicated a typical vertebroplasty setting. Our results showed that the complex viscoelastic behavior of bone cement is significantly affected by deformations and temperature. We found that the results from rotational tests, often used for characterizing the bone cement, are susceptible to measurement artifacts caused by wall slip and "ridge"-like formations in the test sample. We also found the Cox-Merz rule to be conditionally valid, which affects the use of oscillatory tests to obtain the shear-thinning characteristics of bone cement. Our findings identify important differences in the measured flow behavior of PMMA bone cement when assessed by different rheological methods, an understanding that is crucial for its risk-free usage in downstream medical applications.

Cryopreservation of red blood cells (RBCs) plays an indispensable role in modern clinical transfusion therapy. Researchers are dedicated to finding cryoprotectants (CPAs) with high efficiency and low toxicity to prevent RBCs from cryopreservation injury. This study presents, for the first time, the feasibility and underlying mechanisms of a novel CPA called tris(hydroxymethyl)aminomethane-3-propanesulfonic acid (TAPS) in RBCs cryopreservation. The results demonstrated that the addition of TAPS achieved a post-thaw recovery of RBCs at 79.12 ± 0.67%, accompanied by excellent biocompatibility (above 97%). Subsequently, the mechanism for preventing RBCs from cryopreservation injury was elucidated. On one hand, TAPS exhibits a significant amount of bound water and effectively inhibits ice recrystallization, thereby reducing mechanical damage. On the other hand, TAPS demonstrates high capacity to scavenge reactive oxygen species and strong endogenous antioxidant enzyme activity, providing effective protection against oxidative damage. Above all, TAPS can be readily removed through direct washing, and the RBCs after washing showed no significant differences in various physiological parameters (SEM, RBC hemolysis, ESR, ATPase activity, and Hb content) compared to fresh RBCs. Finally, the presented mathematical modeling analysis indicates the good benefits of TAPS. In summary, TAPS holds potential for both research and practical in the field of cryobiology, offering innovative insights for the improvement of RBCs cryopreservation in transfusion medicine.

Eggshell membrane-based biomedical applications have recently received great attention for their wound-healing properties. However, there are limited studies on diabetic wound healing. In this regard, we devised four types of composite eggshell membrane mats with nanoscale coatings of bioactive glass/Zn/Co-doped bioactive glass (ESM + BAG, ESM + ZnBAG, ESM + CoBAG, and ESM + ZnCoBAG) as wound-dressing materials for chronic nonhealing diabetic wounds. A detailed study of the physicochemical properties of the mats was conducted. In vitro studies demonstrated cytocompatibility and viability of human dermal fibroblasts on all four types of mats. The cells also attached finely on the mats with the help of cellular extensions, as evident from scanning electron microscopy (SEM) and rhodamine-phalloidin and Hoechst 33342 staining of cellular components. Endowed with bioactive properties, these mats influenced all aspects of full-thickness skin wound healing in diabetic animal model studies. All of the mats, especially the ESM + ZnCoBAG mat, showed the earliest wound closure, effective renewal, and restructuring of the extracellular matrix in terms of an accurate and timely accumulation of collagen, elastin, and reticulin fibers. Hydroxyproline and sulfated glycosaminoglycans were significantly (p < 0.01, p < 0.05) higher in ESM-ZnCoBAG-treated wounds in comparison to ESM-BAG-treated wounds, which suggests that these newly developed mats have potential as an affordable diabetic wound care solution in biomedical research.

Nanofiber scaffolds have gained significant attention in the field of bone tissue engineering. Electrospinning, a straightforward and efficient technique for producing nanofibers, has been extensively researched. When used in bone tissue engineering scaffolds, electrospun nanofibers with suitable surface properties promote new bone tissue growth and enhance cell adhesion. Recent advancements in electrospinning technology have provided innovative approaches for scaffold fabrication in bone tissue engineering. This review comprehensively examines the utilization of electrospun nanofibers in bone tissue engineering scaffolds and evaluates the relevant literature. The review begins by presenting the fundamental principles and methodologies of electrospinning. It then discusses various materials used in the production of electrospun nanofiber scaffolds for bone tissue engineering, including natural and synthetic polymers, as well as certain inorganic materials. The challenges associated with these materials are also described. The review focuses on novel electrospinning techniques for scaffold construction in bone tissue engineering, such as multilayer nanofibers, multifluid electrospinning, and the integration of electrospinning with other methods. Recent advancements in electrospinning technology have enabled the fabrication of precisely aligned nanofiber scaffolds with nanoscale architectures. These innovative methods also facilitate the fabrication of biomimetic structures, wherein bioactive substances can be incorporated and released in a controlled manner for drug delivery purposes. Moreover, they address issues encountered with traditional electrospun nanofibers, such as mechanical characteristics and biocompatibility. Consequently, the development and implementation of novel electrospinning technologies have revolutionized scaffold fabrication for bone tissue engineering.

Titanium (Ti) and its alloys are widely used biomaterials in bone repair. Although these biomaterials possess stable properties and good biocompatibility, the high elastic modulus and low surface activity of Ti implants have often been associated with infection, inflammation, and poor osteogenesis. Therefore, there is an urgent need to modify the surface of Ti implants, where changes in surface morphology or coatings loading can confer specific functions to help them adapt to the osseointegration formation phase and resist bacterial infection. This can further ensure a healthy microenvironment for bone regeneration as well as the promotion of immunomodulation, angiogenesis, and osteogenesis. Therefore, in this review, we evaluated various functional Ti implants after surface modification, both in terms of static modifications and dynamic response strategies, mainly focusing on the synergistic effects of antimicrobial activities and functionalized osteogenic. Finally, the current challenges and future perspectives are summarized to provide innovative and effective solutions for osseointegration and bone defect repair.

3D bioprinting is recognized as the ultimate additive biomanufacturing technology in tissue engineering and regeneration, augmented with intelligent bioinks and bioprinters to construct tissues or organs, thereby eliminating the stipulation for artificial organs. For 3D bioprinting of soft tissues, such as kidneys, hearts, and other human body parts, formulations of bioink with enhanced bioinspired rheological and mechanical properties were essential. Nanomaterials-based hybrid bioinks have the potential to overcome the above-mentioned problem and require much attention among researchers. Natural and synthetic nanomaterials such as carbon nanotubes, graphene oxides, titanium oxides, nanosilicates, nanoclay, nanocellulose, etc. and their blended have been used in various 3D bioprinters as bioinks and benefitted enhanced bioprintability, biocompatibility, and biodegradability. A limited number of articles were published, and the above-mentioned requirement pushed us to write this review. We reviewed, explored, and discussed the nanomaterials and nanocomposite-based hybrid bioinks for the 3D bioprinting technology, 3D bioprinters properties, natural, synthetic, and nanomaterial-based hybrid bioinks, including applications with challenges, limitations, ethical considerations, potential solution for future perspective, and technological advancement of efficient and cost-effective 3D bioprinting methods in tissue regeneration and healthcare.

In the evolving field of drug discovery and development, multiorgans-on-a-chip and microphysiological systems are gaining popularity owing to their ability to emulate in vivo biological environments. Among the various gut-liver-on-a-chip systems for studying oral drug absorption, the chip developed in this study stands out with two distinct features: incorporation of perfluoropolyether (PFPE) to effectively mitigate drug sorption and a unique enterohepatic single-passage system, which simplifies the analysis of first-pass metabolism and oral bioavailability. By introducing a bolus drug injection into the liver compartment, hepatic extraction alone could be evaluated, further enhancing our estimation of intestinal availability. In a study on midazolam (MDZ), PFPE-based chips showed more than 20-times the appearance of intact MDZ in the liver compartment effluent compared to PDMS-based counterparts. Notably, saturation of hepatic metabolism at higher concentrations was confirmed by observations when the dose was reduced from 200 μM to 10 μM. This result was further emphasized when the metabolism was significantly inhibited by the coadministration of ketoconazole. Our chip, which is designed to minimize the dead volume between the gut and liver compartments, is adept at sensitively observing the saturation of metabolism and the effect of inhibitors. Using genome-edited CYP3A4/UGT1A1-expressing Caco-2 cells, the estimates for intestinal and hepatic availabilities were 0.96 and 0.82, respectively; these values are higher than the known human in vivo values. Although the metabolic activity in each compartment can be further improved, this gut-liver-on-a-chip can not only be used to evaluate oral bioavailability but also to carry out individual assessment of both intestinal and hepatic availability.

Triple-negative breast cancer (TNBC) is an aggressive subtype with the worst prognosis and highest recurrence rates. The treatment choices are limited due to the scarcity of endocrine and HER2 targets, except for chemotherapy. However, the side effects of chemotherapy restrict its long-term usage. Immunotherapy shows potential as a promising therapeutic strategy, such as inducing immunogenic cell death, immune checkpoint therapy, and immune adjuvant therapy. Nanotechnology offers unique advantages in the field of immunotherapy, such as improved delivery and targeted release of immunotherapeutic agents and enhanced bioavailability of immunomodulators. As well as the potential for combination therapy synergistically enhanced by nanocarriers. Nanoparticles-based combined application of multiple immunotherapies is designed to take the tactics of enhancing immunogenicity and reversing immunosuppression. Moreover, the increasing abundance of biomedical materials holds more promise for the development of this field. This review summarizes the advances in the field of nanoparticle-mediated immunotherapy in terms of both immune strategies for treatment and the development of biomaterials and presents challenges and hopes for the future.

Hydrophilic and biocompatible hydrogels are widely applied as ideal scaffolds in tissue engineering. The “smart” gelation material can alter its structural, physiochemical, and functional features in answer to various endo/exogenous stimuli to better biomimic the endogenous extracellular matrix for the engineering of cells and tissues. Light irradiation owns a high spatial-temporal resolution, complete biorthogonal reactivity, and fine-tunability and can thus induce physiochemical reactions within the matrix of photoresponsive hydrogels with good precision, efficiency, and safety. Both gel structure (e.g., geometry, porosity, and dimension) and performance (like conductivity and thermogenic or mechanical properties) can hence be programmed on-demand to yield the biochemical and biophysical signals regulating the morphology, growth, motility, and phenotype of engineered cells and tissues. Here we summarize the strategies and mechanisms for encoding light-reactivity into a hydrogel and demonstrate how fantastically such responsive gels change their structure and properties with light irradiation as desired and thus improve their applications in tissue engineering including cargo delivery, dynamic three-dimensional cell culture, and tissue repair and regeneration, aiming to provide a basis for more and better translation of photoresponsive hydrogels in the clinic.

Proteases play a crucial role, not only in physiological, but also in pathological processes, such as cancer, inflammation, arthritis, Alzheimer’s, and infections, to name but a few. Their ability to cleave peptides can be harnessed for a broad range of biotechnological purposes. To do this efficiently, it is essential to find an amino acid sequence that meets the necessary requirements, including interdependent factors like specificity, selectivity, cleavage kinetics, or synthetic accessibility. Cleavage sequences from natural substrates of the protease may not be optimal in terms of specificity and selectivity, which is why these frequently require arduous and sometimes unsuccessful optimization such as by iterative exchange of single amino acids. Hence, here we describe the systematic design of protease sensitive linkers (PSLs)─peptide sequences specifically cleaved by a target protease─guided by the mass spectrometry based determination of target protease specific cleavage sites from a proteome-based peptide library. It includes a procedure for identifying bespoke PSL sequences, their optimization, synthesis, and validation and introduces a program that can indicate potential cleavage sites by hundreds of enzymes in any arbitrary amino acid sequence. Thereby, we provide an introduction to PSL design, illustrated by the example of matrix metalloproteinase 13 (MMP13). This introduction can serve as a guide and help to greatly accelerate the development and use of protease-sensitive linkers in diverse applications.