•More antimicrobial peptides can be accurately biosynthesized via novel methods and synthetic biology approaches (AMP-BioDesign 2.0), such as computational prediction algorithms, gene editing, and ...cell-free biosynthesis system.•Due to hydrophobic structure with positive charges, AMPs have both broad-spectrum bioactivity and potential biotoxicity problems, which is a balance.•Optimized AMPs have been applied in clinical medicine (for novel drugs), tissue engineering, and drug delivery system for human health.
Antimicrobial peptides (AMPs) are the natural antibiotics recognized for their broad-spectrum resistance to bacteria, fungi, viruses and parasites, and influencing the host immune responses. AMPs attributed to good biological effects have been used in various areas of human health, which are trying to completely replace antibiotics, owing to serious drug-resistance bacteria. However, limited bioactivity and potential biotoxicity of some AMPs was neglected, attributable to their hydrophobic structure with positive charges and nonspecific destruction of cell membranes. Various strategies have been used to design and biosynthetic optimized AMPs to improve their bioactivity, productivity, while lowering host toxicity and cost. Here, we focus on the progress made in understanding the AMPs, including biosynthesis (AMP-BioDesign 1.0 and 2.0), bioactivity (e.g. immune regulation and broad-spectrum or nonspecific actions against bacteria, viruses or parasites), and principle biotoxicity (e.g. hemolysis, acute toxicity and instability, ect). The application prospects of AMP for human health, clinical medicine (for novel drugs), tissue engineering and drug delivery system, respectively, are summarized in this review. Furthermore, future prospects and new strategy for the development of effective and low-toxic AMP formulations for human health are discussed.
Injectable polymer microsphere‐based stem cell delivery systems have a severe problem that they do not offer a desirable environment for stem cell adhesion, proliferation, and differentiation because ...it is difficult to entrap a large number of hydrophilic functional protein molecules into the core of hydrophobic polymer microspheres. In this work, soybean lecithin (SL) is applied to entrap hydrophilic bone morphogenic protein‐2 (BMP‐2) into nanoporous poly(lactide‐co‐glycolide) (PLGA)‐based microspheres by a two‐step method: SL/BMP‐2 complexes preparation and PLGA/SL/BMP‐2 microsphere preparation. The measurements of their physicochemical properties show that PLGA/SL/BMP‐2 microspheres had significantly higher BMP‐2 entrapment efficiency and controlled triphasic BMP‐2 release behavior compared with PLGA/BMP‐2 microspheres. Furthermore, the in vitro and in vivo stem cell behaviors on PLGA/SL/BMP‐2 microspheres are analyzed. Compared with PLGA/BMP‐2 microspheres, PLGA/SL/BMP‐2 microspheres have significantly higher in vitro and in vivo stem cell attachment, proliferation, differentiation, and matrix mineralization abilities. Therefore, injectable nanoporous PLGA/SL/BMP‐2 microspheres can be potentially used as a stem cell platform for bone tissue regeneration. In addition, SL can be potentially used to prepare hydrophilic protein‐loaded hydrophobic polymer microspheres with highly entrapped and controlled release of proteins.
Soybean lecithin (SL)‐mediated nanoporous poly(lactide‐co‐glycolide) (PLGA) microspheres with highly entrapped and controlled released bone morphogenic protein‐2 (BMP‐2) are developed as a stem cell platform. PLGA/SL/BMP‐2 microspheres have excellent in vitro and in vivo cell attachment, cell proliferation, osteogenic differentiation, and matrix mineralization.
Chemical immunosuppressants have been widely used for the treatment of systemic lupus erythematosus (SLE). However, these small chemical drugs suffer from poor solubility, short circulating half-life ...and adverse side effects. One of the most effective strategies to extend the circulating time is loading drugs into nanocarriers to form nanomedicines, which is of particular interest for the treatment of cancer and viral diseases but has seldom been applied to autoimmune disorders. Herein, we successfully developed an easy but general drug delivery platform based on the new biocompatible polyhydroxyalkanoate (PHA) terpolymer poly(3-hydroxybutyrate-
co
-3-hydroxyvalerate-
co
-3-hydroxyhexanoate) (PHBVHHx). In this proof of concept study, we loaded the PHBVHHx nanocarrier with the immunosuppressant azathioprine (AZA) for SLE therapy for the first time. The AZA-PHA nanoparticles possessed ∼30% cytotoxicity and slow clearance from the kidneys. In a murine SLE model, AZA-PHA nanoparticles exhibited superior therapeutic efficacy to AZA and AZA-polylactic acid (PLA) nanoparticles without appreciable toxicity. This delivery system may provide a new and general platform for the development of nanomedicines with enhanced therapeutic efficacy and reduced side effects in SLE therapy.
A polyhydroxyalkanoate terpolymer based drug delivery platform loaded with immunosuppressant for systemic lupus erythematosus therapy with less systemic toxicity.
Microgravity induces a number of significant physiological changes in the cardiovascular, nervous, immune systems, as well as the bone tissue of astronauts. Changes in cell adhesion properties are ...one aspect affected during long-term spaceflights in mammalian cells. Cellular adhesion behaviors can be divided into cell-cell and cell-matrix adhesion. These behaviors trigger cell-cell recognition, conjugation, migration, cytoskeletal rearrangement, and signal transduction. Cellular adhesion molecule (CAM) is a general term for macromolecules that mediate the contact and binding between cells or between cells and the extracellular matrix (ECM). In this review, we summarize the four major classes of adhesion molecules that regulate cell adhesion, including integrins, immunoglobulin superfamily (Ig-SF), cadherins, and selectin. Moreover, we discuss the effects of spaceflight and simulated microgravity on the adhesion of endothelial cells, immune cells, tumor cells, stem cells, osteoblasts, muscle cells, and other types of cells. Further studies on the effects of microgravity on cell adhesion and the corresponding physiological behaviors may help increase the safety and improve the health of astronauts in space.
The treatment of irregular bone defects remains a clinical challenge since the current biomaterials (e.g., calcium phosphate bone cement (CPC)) mainly act as inert substitutes, which are incapable of ...transforming into a regenerated host bone (termed functional bone regeneration). Ideally, the implant degradation rate should adapt to that of bone regeneration, therefore providing sufficient physicochemical support and giving space for bone growth. This study aims to develop an injectable biomaterial with bone regeneration‐adapted degradability, to reconstruct a biomimetic bone‐like structure that can timely transform into new bone, facilitating functional bone regeneration. To achieve this goal, a hybrid (LP‐CPC@gelatin, LC) hydrogel is synthesized via one‐step incorporation of laponite (LP) and CPC into gelatin hydrogel, and the LC gel degradation rate is controlled by adjusting the LP/CPC ratio to match the bone regeneration rate. Such an LC hydrogel shows good osteoinduction, osteoconduction, and angiogenesis effects, with complete implant‐to‐new bone transformation capacity. This 2D nanoclay‐based bionic hydrogel can induce ectopic bone regeneration and promote ligament graft osseointegration in vivo by inducing functional bone regeneration. Therefore, this study provides an advanced strategy for functional bone regeneration and an injectable biomimetic biomaterial for functional skeletal muscle repair in a minimally invasive therapy.
This study develops an injectable biomaterial (LP‐CPC@gelatin, LC) with functional bone regeneration potential, by modulating the LC degradability rate to match bone regeneration, thereby enabling the biomimetic bone‐like structure timely transform into new bone. LC shows good osteoinduction, osteoconduction, and angiogenesis effects, with complete implant‐to‐new bone transformation capacity in ectopic bone regeneration and ligament graft osseointegration in vivo.
Understanding effect of temperature on the molecular self-assembly process will be helpful to unravel the structure–function relationship of biomolecule and to provide important information for the ...bottom-up approach to nanotechnology. In this work, the effect of incubation temperature on the secondary structures and morphological structures of regenerated silk fibroin (RSF) was systematically studied using atomic force microscopy and Fourier Transform infrared spectroscopy. The effect of incubation temperature on RSF self-assembly was dependent on RSF concentration. For the RSF solution with relatively low concentrations (15μg/mL and 60μg/mL), the increase of the incubation temperature mainly accelerated the formation and aggregation of antiparallel β-sheet protofibrils and decreased the formation of random coil protofilaments/globule-like molecules. For the RSF solution with relatively high concentrations (300μg/mL and 1.5mg/mL), the increase of the incubation temperature mainly accelerated the formation and aggregation of antiparallel β-sheet RSF features (protofibrils and globule-like features) and decreased the formation of random coil bead-like features. This work implies that the morphology and conformation of biomacromolecules could be tuned by controlling the incubation temperature. Further, it will be beneficial to basic understanding of the nanoscale structure formation in different silk-based biomaterials.
Abstract
Liquid metal dealloying is a promising technique to produce bicontinuous porous metals with high specific surface areas. This processing technique relies on the selective dissolution of a ...component from a precursor alloy into a metal bath while the remaining insoluble component self-assembles into an interconnected structure. However, it has not been applied to produce nickel-containing porous metals because of the lack of a suitable metallic bath. Here we show that nickel-containing porous metals can be produced by partial liquid metal dealloying. The amount of soluble component in the resulting microstructure can be tuned by carefully choosing the bath element so that the ligaments of desired composition equilibrate with the metal bath. We demonstrate this partial liquid dealloying concept using magnesium and bismuth baths and rationalize the results through thermodynamics calculations. Furthermore, we apply this technique to produce porous nickel-containing stainless steel and high-entropy alloy.
Silk fibroin (SF) is a promising candidate for a variety of application in the fields of tissue engineering, drug delivery, and biomedical optics. Recent research has already begun to explore the ...construction of nano- and micropatterned SF films under ambient environment. The structure and biocompatibility of SF are dependent on SF state (solution or solid) and the method of drying the SF solution to prepare various biomaterials such as films, sponges, and fibers. Therefore, it is important to explore the construction of SF nano- and micropatterns under aqueous solution. This paper reports a novel application of atomic force microscopy (AFM) under liquid for direct deposition of the relatively hydrophobic protein SF onto hydrophilic mica. We demonstrate that the AFM tip, in either the contact or the tapping mode, can fabricate SF micropatterns on mica with controlled surface topography. We show that the deposition process requires a mechanical force-induced SF sol–gel transition followed by a transfer to the mica surface at the tip–surface contact, and the efficiency of this process depends on not only AFM operation mode but also the SF bulk concentration, the SF amount on mica, and the AFM tip spring constant.
The targeted therapeutic effect of nano drug delivery system for glioblastoma has been hampered by the weak enhanced permeability and retention (EPR) effect of glioblastoma and the low delivering ...efficiency of NDDS in glioblastoma tissue. In this study, a tumor-penetrating peptide (RGERPPR), the specific ligand of neuropilin-1 overexpressed on glioblastoma and endothelial cells, was used as a targeting moiety to enhance the anti-glioblastoma effect of doxorubicin liposomes. Firstly, RGERPPR-PEG-DSPE was synthesized and used to prepare the RGERPPR peptide-functionalized liposomes (RGE-LS), which showed vesicle sizes of around 90 nm and narrow size distributions. The cellular uptake and in vivo near-infrared fluorescence imaging test displayed that RGE-LS exhibited increased uptake by glioblastoma cells and intracranial glioblastoma tissues. The cytotoxicity assay and anti-glioblastoma study proved that RGERPPR functionalization significantly enhanced the in vitro inhibitory effect of doxorubicin liposomes on glioblastoma cells and prolonged the median survival time of nude mice bearing intracranial glioblastoma. Finally, the immunofluorescence analysis evidenced that RGE-LS were able to penetrate through tumor vessels and stroma and deep into the whole tumor tissue. The results indicated that tumor-penetrating peptide functionalization is an effective strategy for enhancing the anti-glioblastoma effect of doxorubicin liposomes.
Abstract Significant interest has been expressed by the spinal surgeon community for the use of calcium phosphate cement (CPC) in the treatment of vertebral compression fractures (VCFs), but the ...water-induced collapsibility and poor mechanical properties limit its clinical use. Here we fabricated novel electrospun nanofibrous P(DLLA-CL) balloons (ENPBs) using the nanotechnique of electrospinning. The ENPBs could separate the cements from the surrounding environment, and therefore can prevent the water-induced collapsibility of CPC and eliminate cement leakage. The ENPBs filling with CPC had enough load-bearing ability to restore the height of the fractured vertebral body and had no obvious effects on the initial strength and stiffness of natural bones. Further, the ENPBs had good biodegradability and cell proliferation ability. Calcium can be released from ENPBs filling with CPC. All these results strongly demonstrate ENPBs can be potentially used as CPC filling containers that keep the advantages and eliminate the disadvantages of CPC. From the Clinical Editor Calcium phosphate cement (CPC) is a promising modality in vertebral compression fracture treatment, but its water-induced collapsibility limits clinical applications. This team of investigators fabricated novel nanofibrous balloons using electrospinning, which enabled the separation of CPC from its surrounding environment, and therefore prevented water-induced collapsibility of CPC and eliminated cement leakage while maintaining all the advantages of CPC treatment.
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