Smart Materials in Medicine最新文献

Carbon dots (CDs) are carbon-based zero-dimensional nanomaterials with characteristic sizes of less than 10 ​nm. Recently, bioactive CDs have made remarkable achievements in wound healing, bone and cartilage repair, neural regeneration, and myocardium regeneration owing to their unique physicochemical properties and excellent biocompatibility, which have significantly promoted the advancement of tissue engineering. Herein, we summarize the applications of bioactive CDs in tissue engineering. First, we briefly introduce the characteristics and synthesis methods of bioactive CDs. Subsequently, we review the applications of bioactive CDs in wound healing, bone and cartilage tissue engineering, neural tissue engineering, and cardiac tissue engineering in detail. Finally, we discuss the challenges and prospects of bioactive CDs in tissue engineering.

Facial paralysis is a highly burdening condition, resulting in a patient's inability to move his mimic musculature on one or both sides of his face. This condition compromises the patient's communication and facial expressions, and thus dramatically reduces his quality of life. The current treatment for chronic facial paralysis relies on a complex reconstructive surgery. This publication proposes a novel, less invasive approach for dynamic facial reanimation. The use of a smart material, namely a Dielectric Elastomer Actuator (DEA) is proposed for facial motion restoration, thus avoiding the traditional two-stage free muscle transfer procedure and allowing for a faster recovery of the patient. DEAs are a type of electroactive polymers, showing promising properties similar to natural muscles such as the fact that they are soft, lightweight and allow for large displacements. As a result, a study of the facial muscles and neural interfaces, notably the ones responsible for mouth movement, was performed, in order to implement a realistic setup. In this paper, a non-invasive neural interface based on myoelectric signal is used in order to establish a real-time control of the actuator. Visible motion of a skin model is produced in real time, by synchronizing the actuator to the activity of a healthy muscle, with a maximal delay of 108 ​ms resulting from the signal processing and a delay of less than 30 ​ms related to the actuation of the DEA. This shows that the usage of DEA combined with a neural interface presents a promising approach for treatment of facial paralysis.

Hydrogel-based burn wound dressings with excellent antibacterial, antifungal, and mechanical properties are ideal biomaterials to promote infected large burn wound healing. In this study, the hydrogel synthesized by repetitive freezing-thawing consists of poly (vinyl alcohol) (PVA), silk sericin (SS), and azithromycin (AZM), with genipin (GNP) as crosslinker. The FTIR showed that all hydrogel components were successfully blended. The swelling ratio, porosity, cell attachment, and proliferation improved with SS incorporation, while increased PVA content enhanced the mechanical performance of the hydrogel. The inclusion of AZM improved the antimicrobial property of the hydrogel towards Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. The hydrogel showed sustained SS and AZM releases as well as cytocompatibility on keratinocytes and fibroblasts. Furthermore, the hydrogel displays skin adhesion ability when freeze-dried. In the in vivo study using an infected mouse full-thickness burn model with a 10% total body surface area, it was shown that burn injury led to increased inflammatory cytokine responses and macroscopic and microscopic alterations in the spleen and liver. The kidneys, on the other hand, revealed neither change. Interestingly, the prepared hydrogel had a better burn wound healing effect than the commercial Tegaderm™ film dressing, minimizing systemic burn effects. Hence, this novel hydrogel is projected to be a promising candidate for accelerated healing of infected burn wounds.

Metal materials have been widely applied clinically due to their superior mechanical properties. However, the integration of metallic implants with surrounding soft tissue remains challenging and may lead to severe infections and failure of treatments. Development of natural exemplar suggests that the establishment of the soft tissue integration around hard surfaces is a complex scenario associated with the coordination of epithelial tissue, connective tissue and immune cells. In addition, the influence of the peri-implant immune microenvironment on soft tissue integration reparative process has received increasing attention. Given that the properties of the metal implant could effectively modulate immune response, it is predictable to regulate the immune microenvironment around metal implants for optimized soft tissue integration. This review firstly compared the establishment of natural biological hard surface-soft tissue integration with metal implants, in which the important role of epithelial tissue, connective tissue and immune cells were emphasized. Furthermore, up-to-date research outcomes in the closely connections between the immune microenvironment and soft tissue integration were discussed and summarized. From the view of natural soft-hard tissue integration development and reparative process, the immunomodulation-based strategy is proposed to manipulate the immune microenvironment for the enhancement of soft tissue-metal implant integration.

Peripheral nerve injury (PNI) is a common surgical disease. In recent years, with the development of tissue engineering materials, nerve guidance conduit (NGC) is expected to replace autologous nerve transplantation and become a new method for the treatment of PNI. In this work, we developed a multifunctional silk fibroin (SF)/gelatin-tyramine (GT) composite hydrogel conduit with flexible adjustable size by using a diffusion-driven cross-linking method. Furthermore, the ZIF-8 nanoparticles loaded with miR-29a (miR-29a@ZIF-8) delivery system was constructed and compounded into SF/GT hydrogel conduit to enhance its bioactivity and neural repair effects through sustained miR-29a release. In vitro cell experiments showed that SF/GT hydrogel conduit could significantly promote the myelination of Schwann cells (SCs), neuronal differentiation and axon extension of PC12 ​cells. In addition, it was worth mentioning that SF/GT hydrogel conduit could also regulate the immune microenvironment of nerve regeneration by promoting the transformation of macrophages from M1 phenotype to M2 phenotype, indicating a potential application as nerve guidance conduit in peripheral nerve repair.

Aberrant activation of cell cycle proteins leads to tumor progression in most cancer types. While 5-fluorouracil (5-Fu)-based chemotherapy remains the first-line treatment strategy for colorectal cancer (CRC), more than 40% of patients with advanced CRC do not benefit from the regimen. Herein, a chemically modified curcumin (mCur) was developed to explore its curative effect on CRC and reveal its potential role in cell cycle regulation. Amphiphilic mCur could self-assemble into positively charged nano-micelles, hence facilitating high cellular uptake and anticancer activity. Multi-phase cell cycle arrest, induced by both mCur and Cur, was first observed in HCT 116 ​cells. This phenomenon was mainly attributed to the Cur/mCur mediated downregulation of cyclin-dependent kinases (CDKs) and their direct interactions. Moreover, mCur and Cur treatments generated distinct phenotypic signatures. In particular, mCur induced distinct dynamic fluctuations in cell cycle and a relatively higher proportion of cells in the G2/M phase than Cur, and specifically triggered the impaired expression of polo-like kinase 1 (PLK1). An in vivo evaluation using a CRC patient-derived tumor xenograft (PDX) model indicated that mCur exhibited better antitumor effects via more significant downregulation of PLK1 in PLK1^high PDX, with no obvious systemic toxicity. Collectively, our study revealed a unique multi-phase cell cycle arrest effect of Cur-based antitumor agents and highlighted the potential of mCur as a PLK1-targeted inhibitor for CRC therapy.

Chemodynamic therapy (CDT) has emerged as an effective and safe anticancer therapeutic strategy by catalytic generation of hydroxyl radicals via Fenton chemistry to kill notorious cancer cells. Herein, we decorated the Cu-based nanoparticles with pH-responsive ZnO nanoparticles to give new Zn/Cu nanoparticles (Zn/Cu NPs) which showed good biocompatibility and stability for enhanced therapeutic efficacy of CDT. The newly developed Zn/Cu NPs had a small size of ∼20 ​nm, which could prolong blood circulation time of NPs and facilitate their accumulation in tumor tissues. The mode of therapeutic mechanism was experimentally verified. Upon arriving at the acidic cancer cells, ZnO on Zn/Cu NPs dissolved leading to the release of Cu²⁺ ions which were then reduced by the overexpressed glutathione (GSH), yielding Cu⁺ ions. The presence of Cu⁺ ions favorably catalyzed the conversion of endogenous H₂O₂ into hydroxyl radicals by Fenton-like reactions. Such generated ROS would cause serious oxidative damage to cellular constituents resulting in cell death. Importantly, as the Zn/Cu NPs are pH sensitive, they exhibited much higher cytotoxicity against tumor cells than normal cells. In vivo studies also demonstrated that Zn/Cu NPs could effectively inhibit tumor growth without adverse side effects. Therefore, these Zn/Cu NPs hold great potential for direct and effective tumor therapy for personalized medicine applications.

Periodontal disease is a chronic inflammatory disease that develops from dental plaque that affects periodontal supporting tissues. The control of plaque by mechanical therapy has always been the mainstream of clinical practice. However, studies have shown that both bacteria and oxidative stress are associated with periodontal disease, which means blocking one of them alone may not acquire a better curative effect. The excellent physicochemical properties and biological functions of hydrogels have made them as kinds of ideal biomaterials for periodontal disease in recent years. For these reasons, hydrogels with antimicrobials and antioxidants are considered an effective treatment modality for periodontal disease. Among them, chitosan, cellulose, and other biopolymers have performed their desirable characteristics in the form of hydrogel materials to treat periodontal disease. Here we systematically summarize the current related research and applications of multifunctional hydrogels of antimicrobials and antioxidants in the hope of offering a new idea for new approaches to control periodontal damage.

To optimize synergistic breast cancer treatment, a nanocomposite was fabricated with pH-temperature responsive and chemo-photothermal combination therapy. Herein, gold nanorods (AuNRs) are coated with [poly[(N-isopropylacrylamide)-co-(methacrylic acid)] (p(NIPAM-co-MAA)) modified mesoporous silica (MS) for Doxorubicin (DOX) delivery (AuNR@DOX-MS@p(NIPAM-co-MAA)). Upon NIR radiation, the AuNR core induced hyperthermia via generating heat. Simultaneously, the polymer layer collapsed in response to high temperature/low pH, which allowed the triggering of DOX release from the MS shell at the tumor site. With this nanocomposite, nearly zero premature release of DOX at physiological pH/temperature was detected, while effective DOX release was reported at higher temperature/lower pH values. In addition, in vitro studies demonstrated that the nanocomposite has a substantial uptake efficiency of MDA-MB-231 breast cancer cells, with a significant increase in suppressing MDA-MB-231 ​cell proliferation in response to laser irradiation. The in vivo experiments further verified the high efficiency of the fabricated nanocomposite in accumulating at the tumor site and the good capability in suppressing tumor growth in the mice upon intravenous injection, while exhibiting good biosafety in relation to major organs in the body. Thus, the synthesized nanocomposite could be a potential nanocarrier for breast cancer treatment with synergistic chemo-photothermal therapeutic capability.