A virus‐activated matrix is developed to overcome the challenge of forming vascularized bone tissue. It is generated by filling a 3D printed bioceramic scaffold with phage nanofibers displaying high‐density RGD peptide. After it is seeded with mesenchymal stem cells (MSCs) and implanted into a bone defect, the phage nanofibers induce osteogenesis and angiogenesis by activating endothelialization and osteogenic differentiation of MSCs.
This review presents an overview on the application of latent fingerprint development techniques in forensic sciences. At present, traditional developing methods such as powder dusting, cyanoacrylate fuming, chemical method, and small particle reagent method, have all been gradually compromised given their emerging drawbacks such as low contrast, sensitivity, and selectivity, as well as high toxicity. Recently, much attention has been paid to the use of fluorescent nanomaterials including quantum dots (QDs) and rare earth upconversion fluorescent nanomaterials (UCNMs) due to their unique optical and chemical properties. Thus, this review lays emphasis on latent fingerprint development based on QDs and UCNMs. Compared to latent fingerprint development by traditional methods, the new methods using fluorescent nanomaterials can achieve high contrast, sensitivity, and selectivity while showing reduced toxicity. Overall, this review provides a systematic overview on such methods.
Implantation of stem cells for tissue regeneration faces significant challenges such as immune rejection and teratoma formation. Cell-free tissue regeneration thus has a potential to avoid these problems. Stem cell derived exosomes do not cause immune rejection or generate malignant tumors. Here, exosomes that can induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) are identified and used to decorate 3D-printed titanium alloy scaffolds to achieve cell-free bone regeneration. Specifically, the exosomes secreted by hMSCs osteogenically pre-differentiated for different times are used to induce the osteogenesis of hMSCs. It is discovered that pre-differentiation for 10 and 15 days leads to the production of osteogenic exosomes. The purified exosomes are then loaded into the scaffolds. It is found that the cell-free exosome-coated scaffolds regenerate bone tissue as efficiently as hMSC-seeded exosome-free scaffolds within 12 weeks. RNA-sequencing suggests that the osteogenic exosomes induce the osteogenic differentiation by using their cargos, including upregulated osteogenic miRNAs (Hsa-miR-146a-5p, Hsa-miR-503-5p, Hsa-miR-483-3p, and Hsa-miR-129-5p) or downregulated anti-osteogenic miRNAs (Hsa-miR-32-5p, Hsa-miR-133a-3p, and Hsa-miR-204-5p), to activate the PI3K/Akt and MAPK signaling pathways. Consequently, identification of osteogenic exosomes secreted by pre-differentiated stem cells and the use of them to replace stem cells represent a novel cell-free bone regeneration strategy. 1. Introduction Bone defects can be caused by various clinical diseases such as bone infections, bone tumor, skeletal abnormalities,
Both lytic and temperate bacteriophages (phages) can be applied in nanomedicine, in particular, as nanoprobes for precise disease diagnosis and nanotherapeutics for targeted disease treatment. Since phages are bacteria-specific viruses, they do not naturally infect eukaryotic cells and are not toxic to them. They can be genetically engineered to target nanoparticles, cells, tissues, and organs, and can also be modified with functional abiotic nanomaterials for disease diagnosis and treatment. This Review will summarize the current use of phage structures in many aspects of precision nanomedicine, including ultrasensitive biomarker detection, enhanced bioimaging for disease diagnosis, targeted drug and gene delivery, directed stem cell differentiation, accelerated tissue formation, effective vaccination, and nanotherapeutics for targeted disease treatment. We will also propose future directions in the area of phage-based nanomedicines, and discuss the state of phage-based clinical trials.
The viable use of photodynamic therapy (PDT) in cancer therapy has never been fully realized because of its undesirable effects on healthy tissues. Herein we summarize some physicochemical factors that can make PDT a more viable and effective option to provide future oncological patients with better‐quality treatment options. These physicochemical factors include light sources, photosensitizer (PS) carriers, microwaves, electric fields, magnetic fields, and ultrasound. This Review is meant to provide current information pertaining to PDT use, including a discussion of in vitro and in vivo studies. Emphasis is placed on the physicochemical factors and their potential benefits in overcoming the difficulty in transitioning PDT into the medical field. Many advanced techniques, such as employing X‐rays as a light source, using nanoparticle‐loaded stem cells and bacteriophage bio‐nanowires as a photosensitizer carrier, as well as integration with immunotherapy, are among the future directions.
The antibacterial mechanism of the Cu-containing materials has not been fully understood although such understanding is crucial for the sustained clinical use of Cu-containing antibacterial materials such as bone implants. The aim of this study is to investigate the molecular mechanisms by which the Gram-positive Staphylococcus aureus (S.aureus) is inactivated through Cu-bearing titanium alloys (Ti6Al4V5Cu). Cu ions released from the alloys were found to contribute to lethal damage of bacteria. They destroyed the permeability of the bacterial membranes, resulting in the leakage of reducing sugars and proteins from the cells. They also promoted the generation of bacteria-killing reactive oxygen species (ROS). The ROS production was confirmed by several assays including fluorescent staining of intracellular oxidative stress, detection of respiratory chain activity, and measurement of the levels of lipid peroxidation, catalase and glutathione. Furthermore, the released Cu ions showed obvious genetic toxicity by interfering the replication of nuc (species-specific) and 16SrRNA genes, but with no effect on the genome integrity. All of these effects lead to the antibacterial effect of Ti6Al4V5Cu. Collectively, our work reconciles the conflicting antibacterial mechanisms of Cu-bearing metallic materials or nanoparticles reported in the literature, as well as highlight the potential use of Ti6Al4V5Cu alloys in inhibiting bacterial infections.
Biomacromolecules have been used as templates to grow hydroxyapatite crystals (HAps) by biomineralization to fabricate mineralized materials for potential application in bone tissue engineering. Silk sericin is a protein with features desirable as a biomaterial, such as increased hydrophilicity and biodegradation. Mineralization of the silk sericin from Antheraea pernyi (A. pernyi) silkworm has rarely been reported. Here, for the first time, nucleation of HAps on A. pernyi silk sericin (AS) was attempted through a wet precipitation method and consequently the cell viability and osteogenic differentiation of BMSCs on mineralized AS were investigated. It was found that AS mediated the nucleation of HAps in the form of nanoneedles while self-assembling into β-sheet conformation, leading to the formation of a biomineralized protein based biomaterial. The cell viability assay of BMSCs showed that the mineralization of AS stimulated cell adhesion and proliferation, showing that the resultant AS biomaterial is biocompatible. The differentiation assay confirmed that the mineralized AS significantly promoted the osteogenic differentiation of BMSCs when compared to nonmineralized AS as well as other types of sericin (B. mori sericin), suggesting that the resultant mineralized AS biomaterial has potential in promoting bone formation. This result represented the first work proving the osteogenic differentiation of BMSCs directed by silk sericin. Therefore, the biomineralization of A. pernyi silk sericin coupled with seeding BMSCs on the resultant mineralized biomaterials is a useful strategy to develop the potential application of this unexplored silk sericin in the field of bone tissue engineering. This study lays the foundation for the use of A. pernyi silk sericin as a potential scaffold for tissue engineering.
Here we report the design of a unique matrix, assembled from engineered M13 phage bionanofibers with specific cues of nanotopographies and versatile signal peptides to simulate native niche for directing the fate of induced pluripotent stem cells (iPSCs). By independently varying the peptide sequences and nanotopographies, we find that the resident iPSCs on the phage matrix are first differentiated into mesenchymal progenitor cells (MPCs), which are further differentiated into osteoblasts in the absence of osteogenic supplements due to the elongation induced by phage nanofibers. The phage-based matrix represents not only a biomimetic stem cell niche enabling independently varying biochemical and biophysical cues in one system but also a substrate for generating a safe and efficient cell source for tissue engineering.
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