Smart Materials in Medicine最新文献

Nanoscale metal is considered the backbone of biomedical nanotechnology. Recently, there has been an exponential increase in nanoscale materials’ biomedical applications. These nanomaterials have mainly been employed in drug delivery systems, prosthetic implants, diagnostics, and therapeutics of various diseases, including cancer. Nanoscale materials have two major classes, namely organic and inorganic nanomaterials. Given the merit of excellent biocompatibility, facile synthesis, target recognition, prolonged circulation half-life, and deference to surface functionalization, the inorganic (metallic) nanoparticles hold promising applications in biomedicine. Their biomedical properties may vary based on their type, size, shape, structure, functionalization, and origin. This review will enlighten the recent advances in nanoscale materials applications as nanoscale-knife in cancer theranostics. Moreover, the external assisted technologies and metallic nanoparticle surface decoration will also be highlighted.

Liposome surface potential effect on cellular uptake and cytotoxicity is evaluated using liposomes, modified with cationic lipid DOTAP, a series of cationic gemini surfactants with two carbamate fragments, and an amphiphilic peptide SSRGD. The surfactants used are novel representatives of the gemini family with improved self-assembling activity coupled with potential biodegradable properties and displayed increasing antibacterial activity and cytotoxicity with the shortening of hydrophobic alkyl tails. The longest alkyl tail surfactant, 14-6-14(Et), was the most biocompatible of the series, which was chosen for liposome modification. Prepared liposomes of various compositions are characterized from morphological and physicochemical standpoints in order to optimize their biocompatibility and stability. The carbamate gemini surfactants were also twice as effective at providing positive charge to liposomes and less toxic compared to DOTAP. On their own, carbamate surfactants were able to increase cellular uptake of liposomes by 190%. The mixed composition of 14-6-14(Et) surfactant and SSRGD amphiphilic peptide was the most readily absorbed formulation among different tested neutral, cationic and RGD-modified liposomes. The comparison between the cellular uptake promotion is conducted as to what is the most selective and efficient approach to enhance lipid nanoparticle uptake by cancerous cells.

Nanosized drug delivery systems typically enter the cell via endocytosis. However, a significant amount of the endocytosed cargo cannot effectively escape from the endosome, resulting in drug degradation. Therefore, there are several ongoing efforts to develop transmembrane delivery systems that could circumvent endocytosis. In this study, phospholipid nanotube nanodrills (LDs) were formed onto the surface of a human serum albumin nanoparticle via self-assembling phospholipids. The nanodrill technology enhanced the intracellular uptake efficiency of nanoparticles via energy-independent direct cell membrane permeation. The length of the nanodrills according to the DSPE-PEG to DSPC ratio was investigated both experimentally and theoretically. Our findings demonstrated that longer nanodrills were formed on the surface of the nanoparticles as the ratio of DSPC (i.e., a strongly hydrophobic lipid) in the two phospholipids increases. Moreover, the intracellular uptake efficiency increased as the length of phospholipid nanodrills increased. In addition to enhancing intracellular delivery, the phospholipid nanodrills could penetrate the extracellular matrix and enable the introduction of nanoparticles, thus highlighting the promising tissue penetration capacity of phospholipid nanodrill technology. The improved cell permeability of LD technology was demonstrated by effectively inhibiting specific genes via siRNA-based therapeutic delivery. Moreover, this approach enhanced the efficacy of chemotherapeutics against chemo-resistant cancer cells. Therefore, LD technology could be used to deliver genetic materials and chemical-based therapeutics both in vitro and in vivo.

Bone repair processes are tightly affected by fiber topographies of scaffolds and can be promoted by coupling with chemotactic and/or angiogenic molecules. Here, we developed polycaprolactone (PCL) and collagen-based fibrous scaffolds expressing various architectures via a modified electrospinning set up. We conjugated the as-spun scaffolds with caffeic acid (CA) and/or a cartilage oligomeric matrix protein of angiopoietin 1 (COMP-Ang1). The CA-coupled PCL/collagen scaffold (PCL/col/CA) exhibited greater treatment efficacies for biomimetic and cellular mineralization, expression of osteogenic and chemotactic molecules, and cell migration than did the PCL/col treatment alone. Among the PCL/col/CA scaffolds, the radially symmetric grid-patterned scaffold (rG-PCL/col/CA) showed the greatest bioactivities. The linking of the rG-PCL/col/CA with COMP-Ang1 increased the expression of vascular endothelial growth factor by cells. The COMP-Ang1-linked rG-PCL/col/CA formed more new blood vessels and expressed more chemotactic molecules in a rat model of femoral defects than did the scaffold alone. Compared with PCL/col/CA scaffolds, the COMP-Ang1-coupled rG-PCL/col/CA scaffold stimulated faster and greater healing of femoral defects. Collectively, this study demonstrates that the coupling of a radially grid-patterned fibrous scaffold with CA and COMP-Ang1 greatly enhances scaffold-mediated bone healing via synergistic improvements in vascularization, cell migration, and formation and maturation of new bones in defected regions.

Biomaterials play a pivotal role in modern orthopedics. There are a plethora of functional issues with orthopedic implants. These issues include things like aseptic loosening, lack of osseointegration, biofilm formation, and infections. Researchers have devised several surface modification procedures, including coating the implant surfaces, to address these problems. Implant coatings serve as a bridge between the implant and the surrounding bio components. One of the creative methods is to modify surfaces using smart coatings. Smart coatings can detect environmental cues like temperature, pH, light, and so on and in turn react facultatively to the tissues. A particular stimulus and its specific role in orthopedic implant coatings are of our interest. Some coatings, known as dual-acting coatings, allow for the utilization of one or more stimuli in addition to the individual stimulus as a trigger. Based on the stimuli that they react to, we have highlighted the most cutting-edge smart orthopedic implant coatings in the current review.

Cancer remains the leading cause of death and an important barrier to increase life expectancy. It is desirable to develop therapeutics that can improve life quality and prolong the survival duration. Nano materials have long been considered as a potential tool for detection, diagnosis, and treatment of tumor. The application of nanotechnology for the treatment of cancer is highly based on nano drug delivery system. To meet specific clinical requirements in a superior degree, nanoparticles (NPs) with better biocompatibility, lower toxicity, and definite therapeutic effect are now being developed and designed for experiments and applications. This review presents an overview of the clinical application characteristics of NPs and summarizes the recent advances in the development of nano materials for cancer therapy.

Nowadays, malignant brain tumors are still mostly lethal diseases with poor prognosis and a clinical median survival rate of fewer than 2 years after therapeutic intervention. It is difficult to achieve complete remission of brain tumors due to blood-brain barrier (BBB) and a lack of efficient drug delivery systems to targeted transportation of brain tumor medicines. Nanoparticle delivery systems have shown merits including stability and high carrier capacity for the transportation of different drugs to treat brain tumors. The application of mRNA nanomedicines brings in great promise not only in COVID-19, but also for malignant brain tumor immunotherapy. The appropriate delivery system facilitates mRNA delivery efficiency and enhances the immune response successfully, for optimal treatment outcomes on malignant brain tumors. Herein, we do an updated review on the development of mRNA nanomedicines for malignant brain cancer treatment. We focus on how to design mRNA-loaded nanoparticle-based delivery systems with optimized pharmacokinetics and pharmacodynamics for efficient therapy of brain cancers. In addition, we point out the challenges and solutions for further development of mRNA nanomedicines for brain cancer therapy. We hope this review would stimulate interest among researchers with different backgrounds and expedite the translation from bench to bedside for the mRNA nanomedicines.

Blood glucose (BG) monitoring in patients with diabetes is critical for diabetes management. Minimally invasive BG monitoring is urgently required to increase the patient compliance. Herein, based on a responsive hydrogel system, we developed a smart microneedle patch system for minimally invasive glucose monitoring. The patch consisted of a transparent substrate of photocurable resin and microneedles made of a pH-responsive and glucose-responsive hydrogel. The responsive hydrogel was composed of a photocrosslinkable hydrogel of gelatin methacrylate (GelMA) together with a pH-responsive nanogel (nano(CMC-pHEA)) and glucose oxidase (GOx). The composite hydrogel showed fast response and high sensitivity to glucose levels in physiological range, mainly due to the ionization of CMC-pHEA component and proton balance. The microneedles showed sufficient mechanical strength to penetrate the skin of mice with minimal invasion, and achieved in situ extraction of glucose in interstitial fluid (ISF) and in situ glucose-responsive reaction. We demonstrated the rapid glucose monitoring by microneedle patch system in skin-mimicking gels in vitro and in diabetic mice in vivo. The microneedles quickly and sensitively responded to glucose concentrations, allowed quantitative readouts of glucose levels through the changes of microneedle heights and swelling ratios. Moreover, the readouts in mice in vivo were consistent with BG levels measured by glucometer. This smart microneedle system has potentials to replace blood sampling, and minimize patient discomfort during BG testing, therefore has potentials in minimally invasive, rapid and reliable BG monitoring.

While a significant number of studies have focused on elucidating the functioning mechanisms of the Hepatocellular carcinoma (HCC) microenvironment, the intercellular crosstalk between multiple cells in the tumor microenvironment remains unclear. Here we co-cultured spheroids of HCC cells, hepatic stellate cells (HSCs), and hepatocytes in a biomimetic composite hydrogel to construct a 3D model of the HCC microenvironment in vitro. The model reproduced the major cellular components of early HCC in a biomimetic 3D microenvironment, realizing the visualization of the cellular interplay between cells and the microenvironment. Using this model, we showed that the HSCs were activated when co-cultured with HCC cells and deposed collagen to remodel the microenvironment, which in turn triggered higher EMT levels in HCC cells. The hepatocytes also responded to the existence of HCC cells and the activation of HSCs in co-culture, showing the downregulated expression level of ALB, AFP, and HNF4A. This model recapitulated the activation of HSCs in the HCC microenvironment and enabled visualization of multicellular interplay in 3D, providing a biomimetic platform to investigate mechanisms of HCC and related hepatic fibrosis.

Based on their excellent biocompatibility and adjustable biodegradability, the two natural polyesters polylactic acid (PLA) and polyhydroxyalkanoates (PHAs) have been widely used in medical engineering and regenerative medicine. Different types of natural biopolyester microspheres (NBPMs) composed of PLA, PHAs and their derivatives have been designed and used in diverse micro-devices in the last few decades, offering promise for diverse biomedical applications. In addition to biocompatibility and biodegradability, the structure and surface topology of NBPMs also affects in vitro and in vivo cell behaviors such as proliferation, metabolism and differentiation, which are often neglected. In this review, we summarized the preparation methods and properties of diverse NBPMs, including solid, hollow, open porous, and nanofibrous structures, as well as smooth, golf-ball-like, wrinkled, convex, rough and Janus surface topologies, respectively. Moreover, the advantages and limitations of NBPMs for medical applications are analyzed, including tissue engineering (e.g., regeneration of bone, cartilage, liver, tooth, myocardium, and skin), cell engineering for in vitro 3D cell culture, transportation, and cryopreservation, as well as different drug-release models. Finally, we discuss possible future applications of NBPMs with novel, more complex surface structures in light of current trends in biomedicine.