Smart Materials in Medicine最新文献

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.

Cell sheet engineering is a rapidly growing field of tissue engineering and regenerative medicine. The ease of cell sheet obtainment techniques and the resulting unique characteristics and microenvironment of these multicellular structures give rise to the wide range of their in vivo application. At the same time, there are also macroscale cell sheet properties such as thickness, shrinkage after detachment due to cytoskeleton relaxation, and resulting mechanical characteristics. The main topic of this review is the discussion of these properties and how they define the need to use special approaches to manipulating cell sheets during stacking several structures, transferring them to surgical sites, or cryopreserving them. We aimed to systematize the existing techniques of cell sheet transferring, and describe their principles, advantages, and drawbacks regarding cell sheet application during surgical procedures on various tissues and organs. Attention is also paid to such aspects and details as cell sheet positioning in vivo, their ability to spontaneous adhesion, and the requirement for additional fixation at particular surgical sites. Finally, the last section of this review covers the subject of cell sheet cryopreservation – the discussion of freezing and thawing protocols, the variety of cryoprotectants and their mixtures, as well as special requirements such as cryoprotectant loading systems, and cell sheet supporting systems that also stem from their unique macroscale characteristics. Altogether, this systematized review of existing technological approaches related to cell sheet application in vivo can be potentially helpful for the new and expert researchers in this area of tissue engineering.

Mesenchymal stem cell exosomes (MSC-Exos) are a type of cell vesicle with biological function secreted by mesenchymal stem cells (MSCs). In tissue repair, MSC-Exos are more effective than MSCs, and they can be used as a cell-free alternative therapy to MSCs. This therapeutic system has a stable membrane structure that is coated with proteins, miRNAs, mRNA, lncRNA, DNA, and other macromolecular active substances. These molecules have a powerful effect on tissue regeneration. MSC-Exos can regulate the biological function of target cells through direct recognition, membrane fusion, and secretion of communication mediators. Skin wound healing consists mainly of blood coagulation, inflammation response, cell proliferation, and tissue remodeling. By regulating the four stages of wound healing, MSC-Exos effectively reduce tissue inflammation, reduce the immune response, promote enhanced cell migration and angiogenesis and regulate tissue remodeling, thus shortening the healing time and reducing scar formation. A variety of biological factors, genetic material and signaling pathways are involved in this process. This article reviews the efficacy and mechanism of MSC-Exos in promoting skin tissue repair.

Bacterial cellulose (BC) possesses the desirable properties of biocompatibility, high porosity, high surface area and noticeable mechanical strength as a scaffold in bone tissue engineering. However, the lack of osteogenic activity restricts its application. In this study, gold nanoparticles (GNPs) with excellent osteogenic differentiation ability were incorporated into the network of BC hydrogel (Au/BC hydrogels) by the in-situ fermentation. The effects of GNPs on physicochemical properties of BC hydrogel and subsequently in vitro osteogenic differentiation and in vivo bone regeneration of Au/BC hydrogels were comprehensively investigated. The results showed that the increased feeding amounts of GNPs could remarkablly enhance the Au/BC hydrogels with better mechanical properties, higher porosity, larger surface area, and biocompatibility. The sustainable release of GNPs endowed the hydrogels with an outstanding biological activity in facilitating osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Mechanism research showed that autophagy might be a potential pathway for Au/BC hydrogels-induced osteogenic differentiation of hBMSCs. In addition, Au/BC hydrogel exhibited an excellent in vivo bone repair performance in a rabbit model of femoral defect, which was evidenced by the significant newly bone formation. Overall, the multifunctional Au/BC hydrogels fabricated by in-situ fermentation could serve as a good scaffold for promoting bone tissue regeneration in clinic.

Bone regeneration scaffolds loaded with osteoblast-related cells or cytokines exhibit outstanding therapeutic potential during large-scale bone defect repair. However, limited sources of cells, opportune choosing of growth factors and their concentration, as well as immunological rejection, seriously hinder its clinical application. Developing a scaffold that can effectively recruit MSCs in situ and achieve endogenous bone regeneration is a viable strategy. Herein, we report a chitosan-calcium carbonate scaffold with high mineral content and centripetal pore arrangement using a simple in situ mineralization method. In vivo results first time demonstrate that the scaffold with high calcium carbonate content can effectively recruit MSCs near the defect area, induce their osteogenic differentiation, and ultimately accelerate the process of bone regeneration. Considering the accessible preparation and excellent osteogenicity, the chitosan-calcium carbonate scaffold possesses high potential for the therapeutics of massive bone defects.

The study of synthetic biology focusing on biosensor systems has resulted from a growing interest in developing customized biological devices with desired cellular functions. Recently, biosensors have been used for a variety of medical applications such as disease diagnosis, prevention, rehabilitation, patient health monitoring, and human health management. Meanwhile, the ability to track biomarkers based on biosensors allows researchers and medical practitioners to provide patients with individualized treatment regimens and health management. Biosensors that respond to electrochemical, optical, thermal, piezoelectric and magnetic signals have been developed and utilized for various disease therapies and biomedical applications. This study reviews recent developments in biosensor-based therapeutic tools by sensing diverse biomarkers in many diseases (e.g. cancer, infections, metabolic diseases), such as physical biomarkers (e.g. pressure, temperature) and chemical biomarkers (e.g. dissolved oxygen, glucose). Additionally, we highlight the challenges and problems of biosensor-based therapeutics and possible solutions for biosensor engineering thereof. Current biosensors enable for coarsely programable personal treatment and health management, however, new sensors with optimized dose-response functions, for example, fast response and tight-control performances, could significantly boost versatile uses in medical treatment in the coming future.