Smart Materials in Medicine最新文献

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.

Rapid hemostasis and effective healing for the non-compressible liver wounds which are not able to be sewn, especially for those large-area wounds, remain great clinical challenges. In this study, we fabricated epidermal growth factor (EGF)-loaded chitosan microspheres (CM) and then incorporated them into a photo-crosslinking gelatin methacryloyl (GelMA) hydrogel. The results showed that the EGF-loaded CM/GelMA precursor solution could transform into a hydrogel and cease bleeding at laceration sites without external stress. Subsequently, the sustained release of EGF accelerated wound closure and promoted liver regeneration. The in vitro experiments demonstrated that the microsphere/hydrogel composite could promote the proliferation and migration of L02 ​cells. Moreover, the histological and immunohistological analyses indicated that EGF-CM/GelMA composite could alleviate inflammation in the mouse liver and promote liver remodeling. Overall, this multi-functional microsphere/hydrogel composite will inspire the development of clinical applications for noncompressible hemostasis and successive wound closure.

With the advent of nanotechnology, incorporating nanoscale fillers in dental resins seems promising to improve therapeutic features and provide more excellent physicochemical properties for dental materials. The use of nanotubes has been raised due to their excellent mechanical properties, carry and delivery of drugs capabilities, and bioactive properties. These features depend on the composition of nanotubes and their application. This scoping review aims to describe previous studies about incorporating nanotubes in restorative resin-based materials. The main goals here addresses are: (1) to identify which are the most used nanotubes in the development of these dental materials; (2) to verify which the molecules/particles associated with these nanotubes; (3) to report the objectives of the incorporation of nanotubes to these dental materials and main results. The searches were performed using PubMed and Scopus databases in December 2022, identifying 534 manuscripts. After the selection process, 43 studies were included in the review. We mainly analyzed and discussed the nanotubes' composition, the parental materials in which the nanotubes were incorporated, the purposes of adding these particles to the dental materials, how the materials were analyzed, and the primary studies' outcomes. The outcomes are stimulating and reveal a promising advance in dental resins with the possibility of improving the maintenance of restorations and patients' quality of life. Further studies should address the abovementioned topics to expand the understanding and options of using nanotubes in resin-based restorative materials.