Smart Materials in Medicine最新文献

Acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), is the major cause of intensive care unit death worldwide. ALI/ARDS is a common condition characterized by a storm of potent inflammatory cytokines. Lung delivery of glucocorticoids (GCs) by inhalation is a potential approach for ALI treatment and ARDS prevention; however, its efficacy is limited by the rapid clearance of GCs in lungs. In this study, we developed surface-modified poly(lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with bioadhesive properties for local delivery to the epidermis of lung tissues, which exhibited prolonged release profile of payloads following intratracheal spraying administration. Compared with that of non-adhesive nanoparticles (NNPs), BNPs showed significantly enhanced adhesion and prolonged retention within lung tissues in vivo. Lipopolysaccharide (LPS)-induced ALI mice treated with betamethasone dipropionate (BD)-loaded BNPs showed significantly fewer lung histological alterations and less lung inflammation than those administered free BD or BD-loaded NNPs, indicating the enhanced therapeutic efficacy of BD/BNPs in ALI. In contrast, the features of ARDS were observed in the animal models without any treatments. Our findings demonstrated that pulmonary delivery of BNPs can maintain their same surface structures and continuously form covalent connections with the contacted tissues, emphasizing their potential to improve the therapeutic efficacy in ALI and prevent from ARDS.

Diabetes mellitus (DM) is a chronic metabolic disorder that can affect the balance of bone metabolism and bone microenvironment, leading to impaired fracture healing. There are several underlying mechanisms which contributing to the impaired diabetic bone microenvironment such as hyperglycemia, the production of advanced glycation end products (AGEs), inflammation, and oxidative stress, etc. Recent studies have achieved great progress in developing novel smart biomaterials in improving the diabetic bone microenvironment to promote diabetic fracture healing. In this paper, we reviewed the mechanisms on DM-induced impaired fracture healing. Meanwhile, we also summarized the smart biomaterials used to improve the local microenvironment of diabetic fractures healing, which provides a novel perspective for the future treatment of fractures in diabetic patients.

Macroporous cryogel has the advantages of nutrient exchange and cell growth, and is an ideal material for tissue regeneration. In order to strengthen the machenical properties of cryogel for the widely use, a high strength gelatin/sodium alginate/nano hydroxyapatite (nHA) porous cryogel (GA-HA cryogel) was prepared by a simple freeze-thaw process. The mechanical strength of GA-HA cryogel increased significantly with the increase of nHA content. In vitro studies showed that GA-HA cryogel had good biocompatibility and no obvious cytotoxicity to MC3T3-E1 cells. The results of alkaline phosphatase activity assay and osteocalcin immunofluorescence staining showed that GA-HA1 porous hydrogel system could significantly increase the expression of MC3T3-E1 alkaline phosphatase and osteocalcin when the content of nHA was 1 ​%. In addition, porous GA-HA cryogel showed good performance in promoting bone regeneration in rat skull defect model. Therefore, the high-strength double network cryogel prepared in this study can provide new applications in bone repair and tissue regeneration.

Hyper-uric acid (UA)-induced kidney injury (HAKI) is caused by the deposition of excess blood UA into the kidneys. We confined molecules of uricase (URI), catalase (CAT), and curcumin (Cur) to a single structure (UC/Cur) while retaining their enzymatic activities via a cross-linking complexation reaction between tannic acid and FeCl₃ for treating HAKI. Simultaneously, bovine serum albumin (BSA)-UC/Cur nanoparticles were successfully prepared by interlinking the disulfide bonds of BSA with the enzyme complex via Tris(2-carboxyethyl) phosphine(TCEP) to form sulfhydryl groups. BSA-UC/Cur significantly attenuated MSU-induced NLRP3 inflammasome pathway activation and apoptosis in NRK-52e cells by eliminating UA crystals and intracellular reactive oxygen species. More importantly, treatment with BSA-UC/Cur stabilized blood UA concentrations and lowered proximal tubular protein levels, mitochondrial swelling, and fibrotic areas, renducing the expression of matrix metalloproteinase (MMP)2, MMP9, and NLRP3 while, increasing the expression of tight-junction proteins ZO1 and occludin as well as that of TIMP-1, in HAKI model rats. In addition, BSA-UC/Cur nanoparticles reduced the subpopulation ratios of CD8⁺ T cells and M1 macrophages and increased those of M2 macrophages and Treg cells. Preliminary in-vivo trials showed that long-term intravenous treatment with BSA-UC/Cur is safe. Therefore, BSA-UC/Cur could be a potential nanotherapeutic agent for HAKI.

Lung cancer has surpassed other types of cancer to become the primary cause of cancer-related deaths. Surgery stands as the foremost clinical treatment strategy available for tackling this condition, but it receives a low efficiency for most patients. In recent years, some adjuvant therapies are employed to improve the lung cancer treatment efficiency, such as chemotherapy, targeted therapy and immunotherapy. However, these strategies have not significantly increased overall survival of patients. Additionally, the random distribution of drugs will induce severe side effects. Nanomedicines have got great attentions to boost drug effect and reduce adverse reactions, including liposome-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and exosomes. Importantly, nanomedicines contribute to improving drug bioavailability, stability and residency in target regions. Benefiting from the physiological characteristics of lung, the inhaled pulmonary delivery strategy in combination with nanomedicine will provide a non-invasive and effective strategy for treating lung cancer. Furthermore, the use of targeting ligands enables precise delivery of loaded drugs to lung cancer cells. Inhaled nanomedicine exhibits unique distribution and sustained release behaviors in the alveoli, amplifying the therapeutic effect and reducing side effects. This review aims to discuss various inhaled methods of delivering nanomedicine to treat lung cancer and also summarizes the clearance mechanism of nanomedicine in the lung. Overall, this review focuses on the application of different inhalable nanomedicines, which may inspire the development of more effective treatments against lung cancer.

Acromegaly is a challenging medical condition that arises from the excessive production of growth hormones and the insulin-like growth factor 1 in the pituitary gland. While surgery is the primary treatment for acromegaly, medication is increasingly being used in patients who are unsuitable for surgery or have experienced treatment failure. Despite advancements in medical and surgical therapies, the treatment of acromegaly remains challenging. In this research, a three-dimensional (3D) in-vitro cell culture model for pituitary adenoma research was developed using hydrogel fiber meshes (HFMs) and GH3 cells. Electrospun nanofibers based on polyvinyl alcohol and polyacrylic acid were converted into HFMs by hydrogelification with the leaching of electrosprayed cellulose acetate beads for porosity enhancement. GH3 cells grown in the 3D model exhibited increased dispersion and upregulation of the somatostatin receptor subtypes 2 and 5 compared to those grown in traditional 2D cultures, as well as high sensitivity to somatostatin analogs and tumor-like profiles (as indicated by functional assays and transcriptome analysis, respectively). Therefore, the proposed 3D model accurately represents the physiological response to pituitary-adenoma therapeutic agents. This study highlights the potential of HFMs as a versatile platform for 3D in-vitro cell culture models that can be employed for pituitary adenoma research. Moreover, the proposed 3D cell culture model may contribute to a deeper understanding of tumor biology and facilitate the development of effective therapeutic strategies for acromegaly.

Over the past decades, increasing evidence has indicated that multiple mechanical signals with different magnitude and pattern, including fluid flow-derived shear stress, topology of extracellular matrix (ECM), substrate stiffness, tension or compression, are now emerging as important orchestrators of immune response under physiological and pathophysiological conditions. Correspondingly, the extrinsic mechanical signals may confer the unique mechanophenotypes on cells, which coupled with their immunophenotypes, determines the ultimate type of immune response. Therefore, the concept of mechano-immunological checkpoints is proposed, which concerns the featured mechanical signals and the typical mechanophenotypes of immune cells, making it possible to elucidate and treat immune-associated disease from the mechanical viewpoint.

Although characterized by high reactive oxygen species (ROS) generation, cancer cells maintain redox homeostasis to avoid severe damage (e.g., DNA, protein, and plasma membrane dysfunction) and facilitate cancer progression. Emerging evidence has indicated that targeting the regulation of redox homeostasis to amplify oxidative stress is of value in cancer therapy. However, therapeutic agents like nucleic acids, small molecular inhibitors, and chemotherapeutic drugs fail to exert effective cancer inhibition due to their low bioavailability, susceptibility to serum enzymes, and inefficiency in cell membrane penetrating. Therefore, specific delivery vectors are required to facilitate the intracellular delivery of anti-tumor drugs. In the past few decades, various engineered nanomaterials have been designed and developed for drug delivery. In particular, rational nanoparticles (NPs) have garnered more attention due to their splendid long circulation ability, modification capacity, and stimulation-responded release. In this review, the methods of ROS generation and ROS-regulated signaling in cancer development were firstly briefly introduced. The anti-oxidant system, including the metabolism shifting and anti-oxidant genes, were next reviewed, and the strategies of NPs-mediated targeted regulation of redox homeostasis were emphatically discussed. The main strategies include NPs-induced delivery of nucleic acids, small molecule inhibitors, chemotherapeutic agents, radiosensitizers, and NPs-induced ROS generation and GSH depletion. The future development of NP-mediated redox dyshomeostasis in cancer therapy and their challenges in clinical translation were finally discussed.

With the rapid progress of information technology and life sciences, artificial intelligence (AI) technology has substantially changed the way in many areas of biomaterials and biomedicine, including biomaterials and formulation design, drug development, preclinical study, clinical diagnosis and treatment, as well as health management. This perspective outlines the key issues of AI in the fields of biomaterials and biomedicine applications, and analyzes some opportunities and challenges of AI in the biomedical and clinical development. The gap between experts from multiple disciplines and fields needs to be narrowed, and common participation should be applied to open the next frontier of integrated AI-biomedicine.