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Biomimetic cell‐membrane‐camouflaged nanoparticles with desirable features have been widely used for various biomedical applications. However, the current research focuses on single cell membrane coating and using multiple cell membranes for nanoparticle functionalization is still challenging. In this work, platelet (PLT) and leukocyte (WBC) membranes are fused, PLT–WBC hybrid membranes are coated onto magnetic beads, and then their surface is modified with specific antibodies. The resulting PLT–WBC hybrid membrane‐coated immunomagnetic beads (HM‐IMBs) inherit enhanced cancer cell binding ability from PLTs and reduce homologous WBC interaction from WBCs, and are further used for highly efficient and highly specific isolation of circulating tumor cells (CTCs). By using spiked blood samples, it is found that, compared with commercial IMBs, the cell separation efficiency of HM‐IMBs is improved to 91.77% from 66.68% and the cell purity is improved to 96.98% from 66.53%. Furthermore, by using the HM‐IMBs, highly pure CTCs are successfully identified in 19 out of 20 clinical blood samples collected from breast cancer patients. Finally, the robustness of HM‐IMBs is verified in downstream CTC analysis such as the detection of PIK3CA gene mutations. It is anticipated that this novel hybrid membrane coating strategy will open new possibilities for overcoming the limitations of current theranostic platforms.  相似文献   

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Mechanical mismatch and the lack of interactions between implants and the natural tissue environment are major drawbacks in bone tissue engineering. Biomaterials mimicking the self‐assembly process and the composition of the bone matrix should provide new routes for fabricating biomaterials possessing novel osteoconductive and osteoinductive properties for bone repair. In the present study, bioinspired strategies are employed to design de novo self‐assembled chimeric protein hydrogels comprising leucine zipper motifs flanking a dentin matrix protein 1 domain, which is characterized as a mineralization nucleator. Results show that this chimeric protein could function as a hydroxyapatite nucleator in pseudo‐physiological buffer with the formation of highly oriented apatites similar to biogenic bone mineral. It could also function as an inductive substrate for osteoblast adhesion, promote cell surface integrin presentation and clustering, and modulate the formation of focal contacts. Such biomimetic “bottom‐up” construction with dual osteoconductive and osteoinductive properties should open new avenues for bone tissue engineering.  相似文献   

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Stem cells have demonstrated values in diabetic ulcer (DU) treatments. Challenges in this area are focused on enhancing the localized curative effects of stem cells and improving diabetic wound healing efficiently. Herein, a novel living microneedle (MN) patch is presented as a localized delivery system of bioactive platelet derived growth factor D (PDGF-D) and human adipose-derived stem cells (ADSCs) for DU wound treatment. Compared with traditional complicated stem cell carriers, the MN patch can keep stem cell viability for ADSCs encapsulation and delivery, and possesses good mechanical strengths to penetrate the local skin wounds noninvasively. It is demonstrated that the delivery ADSCs are with the abilities of angiogenesis promotion during the DU wound healing; while the additive PDGF-D can contribute significantly to the proliferation of ADSCs, strengthening the cell function of ADSCs and further facilitating the healing processes. Thus, living MN patches accelerate vascularization, tissue regeneration, and collagen deposition in a wounded diabetic mouse model, suggesting their potential application to DU wound healing and other therapeutic applications.  相似文献   

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Bioinspired design is an engineering approach that involves working to understand the design principles and strategies employed by biology in order to benefit the development of engineered systems. From a materials perspective, biology offers an almost limitless source of novel approaches capable of arousing innovation in every aspect of materials, including fabrication, design, and functionality. Here, recent and ongoing work on the study of bioinspired materials for sensing applications is presented. Work presented includes the study of fish flow receptor structures and the subsequent development of similar structures to improve flow sensor performance. The study of spider air‐flow receptors and the development of a spider‐inspired flexible hair is also discussed. Lastly, the development of flexible membrane based infrared sensors, highly influenced by the fire beetle, is presented, where a pneumatic mechanism and a thermal‐expansion stress‐mediated buckling‐based mechanism are investigated. Other areas that are discussed include novel biological signal filtering mechanisms and reciprocal benefits offered through applying the biology lessons to engineered systems.  相似文献   

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Nucleic acids are gaining significant attention as versatile building blocks for the next generation of soft materials. Due to significant advances in the chemical synthesis and biotechnological production, DNA becomes more widely available enabling its usage as bulk material in various applications. This has prompted researchers to actively explore the unique features offered by DNA‐containing materials like hydrogels. In this review article, recent developments in the field of hydrogels that feature DNA as a component either in the construction of the material or as functional unit within the construct and their biomedical applications are discussed in detail. First, different synthetic approaches for obtaining DNA hydrogels are summarized, which allows classification of DNA materials according to their structure. Then, new concepts, properties, and applications are highlighted such as DNA‐based biosensor devices, drug delivery platforms, and cell scaffolds. With the 2018 Nobel Prize in Physiology or Medicine being awarded to cancer immunotherapy underscoring the importance of this therapy, DNA hydrogel systems designed to modulate the immune system are introduced. This review aims to give the reader a timely overview of the most important and recent developments in this emerging class of therapeutically useful materials of DNA‐based hydrogels.  相似文献   

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With the remarkable development of DNA nanotechnology, interest in DNA molecules has expanded beyond its biological role to building blocks in materials science. As a unique branch of DNA-based materials, DNA hydrogels have exhibited many fascinating characteristics, including broad biocompatibility, precise programmability, convenient modification, and tunable mechanical properties, which make DNA hydrogels ideal biomaterials. Moreover, by combining with functional nucleic acids, such as aptamers, i-motif nanostructures, CpG oligodeoxynucleotides, and DNAzymes, DNA hydrogels can be further tailored to provide additional target recognition, therapeutic potential, and catalytic activities, allowing them to play important roles in biosensing and medical applications. This review, aims to provide readers with an up-to-date overview of the important developments of biomedical DNA hydrogels. First, it introduces different synthetic strategies of hydrogels that utilize DNA as building materials and functional units within the hydrogel networks and discuss their advantages in biomedical applications. Subsequently, new approaches and applications of biomedical DNA hydrogels in the recent years are highlighted, such as therapeutic systems, cell culture platforms, tissue engineering materials, and biosensors. Finally, future perspectives and remaining challenges of DNA hydrogels in biomedicine are presented.  相似文献   

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Unique microneedle arrays prepared from crosslinked polymers, which contain no drug themselves, are described. They rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch‐type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilized, resist hole closure while in place, and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically modulated delivery is also a unique feature. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of the type of drug that is deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients.  相似文献   

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Deciphering the roles of chemical and physical features of the extracellular matrix (ECM) is vital for developing biomimetic materials with desired cellular responses in regenerative medicine. Here, it is demonstrated that sulfation of biopolymers, mimicking the proteoglycans in native tissues, induces mitogenicity, chondrogenic phenotype, and suppresses catabolic activity of chondrocytes, a cell type that resides in a highly sulfated tissue. Through tunable modification of alginate it is shown that increased sulfation of the microenvironment promotes fibroblast growth factor (FGF) signaling‐mediated proliferation of chondrocytes in a 3D matrix independent of stiffness, swelling, and porosity. Furthermore, for the first time it is shown that a biomimetic hydrogel acts as a 3D signaling matrix to mediate a heparan sulfate/heparin‐like interaction between FGF and its receptor leading to signaling cascades inducing cell proliferation, cartilage matrix production, and suppression of dedifferentiation markers. Collectively, this study reveals important insights on mimicking the ECM to guide self‐renewal of cells via manipulation of distinct signaling mechanisms.  相似文献   

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Most vaccines are designed to attack tumor cells by activating CD4+/CD8+ αβ T cells. Unfortunately, αβ T cells, which only recognize the peptide antigens in the complexes with polymorphic MHCI/II molecules, surrender to the tumor heterogenicity. As another subset of T cells, γδ T cells become salient in antitumor because of their unique immunotherapeutic roles. Herein, a tumor vaccine is developed with multivalent antigens by fusion of tumor cell membranes with lipids and successfully activated γδ T cells via microneedle inoculation. It is certified that the evoked γδ T cells synchronize with αβ T cells revitalizing tumor-induced immunotolerance. In turn, the tumors of mice are significantly inhibited and their median survival time is prolonged considerably. Moreover, the nanovaccine inhibits tumor recurrence after resection. The therapeutic effects are corroborated with the results from TCRδ−/− mice as well as cytokine expression in tumor.  相似文献   

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Cell encapsulation within hydrogel droplets is transforming what is feasible in multiple fields of biomedical science such as tissue engineering and regenerative medicine, in vitro modeling, and cell-based therapies. Recent advances have allowed researchers to miniaturize material encapsulation complexes down to single-cell scales, where each complex, termed a single-cell microgel, contains only one cell surrounded by a hydrogel matrix while remaining <100 μm in size. With this achievement, studies requiring single-cell resolution are now possible, similar to those done using liquid droplet encapsulation. Of particular note, applications involving long-term in vitro cultures, modular bioinks, high-throughput screenings, and formation of 3D cellular microenvironments can be tuned independently to suit the needs of individual cells and experimental goals. In this progress report, an overview of established materials and techniques used to fabricate single-cell microgels, as well as insight into potential alternatives is provided. This focused review is concluded by discussing applications that have already benefited from single-cell microgel technologies, as well as prospective applications on the cusp of achieving important new capabilities.  相似文献   

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Circulating tumor cells (CTCs) are a crucial biomarker for early cancer diagnosis and progress of cancer metastasis. However, the extremely rare CTCs with large amounts of background leukocytes seriously restricte the purity of enriched CTCs. Herein, genetically engineered cell membrane-coated magnetic nanoparticles with following properties are constructed: I) The leukocyte membrane camouflaged nanoparticles, which could significantly reduce nonspecific binding of homologous leukocytes and achieve high-purity isolation of CTCs, are prepared by simple one-step extrusion and II) the cellular membrane stably expressing single-chain variable fragment (scFv) of anti-epidermal growth factor receptor (EGFR) antibody could ensure the recognition of EGFR-positive CTCs. The binding affinity of the resulting nanoparticles toward extracellular EGFR protein improved more than 100-fold compared with natural cell membrane-coated nanoparticles. Furthermore, compared with commercial immunomagnetic nanoparticles, the functional nanoparticles achieved a greater capture efficiency in artificial blood samples and the cell purity increased from 64.8% to 93.5%. Consequently, the authors successfully isolate high pure CTCs from 6 out of 6 cancer patients using engineered cell membrane-coated nanoparticles. This platform exhibits a promising potential for CTC detection in clinical samples, offering an innovative method for cancer diagnosis and prognosis evaluation.  相似文献   

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The mechanical holdfast of the mussel, the byssus, is processed at acidic pH yet functions at alkaline pH. Byssi are enriched in Fe3+ and catechol‐containing proteins, species with chemical interactions that vary widely over the pH range of byssal processing. Currently, the link between pH, Fe3+‐catechol reactions, and mechanical function is poorly understood. Herein, it is described how pH influences the mechanical performance of materials formed by reacting synthetic catechol polymers with Fe3+. Processing Fe3+‐catechol polymer materials through a mussel‐mimetic acidic‐to‐alkaline pH change leads to mechanically tough materials based on a covalent network fortified by sacrificial Fe3+‐catechol coordination bonds. These findings offer the first direct evidence of Fe3+‐induced covalent cross‐linking of catechol polymers, reveal additional insight into the pH dependence and mechanical role of Fe3+‐catechol interactions in mussel byssi, and illustrate the wide range of physical properties accessible in synthetic materials through mimicry of mussel‐protein chemistry and processing.  相似文献   

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A strategy is proposed to achieve an enhanced capture efficiency of and low damage to human leukemic lymphoblasts (CCRF‐CEM) by the synergistic effect of topographical interactions and phenylboronic acid functional groups on nanostructures. To realize this purpose, a simple and template free method to synthesize boronic acid derivative polyaniline bioinspired nanostructures with controlled morphology is established. Different nanostructured morphologies such as nanotexture, nanofibers, nanoparticles, microsphere, and 3D porous network have been prepared by controlling the nucleation and growth rate for polymerization. The phenylboronic acid functional groups on the surface of the nanostructures during poly­merization are used as artificial lectins to reversibly capture and release circulating tumor cells (CTCs) with little damage to the cells. The method presented here is simple, rapid, and highly efficient for CTC capture and release with low cost in materials and instruments.  相似文献   

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Growth factor activity is localized within the natural extracellular matrix (ECM) by specific non-covalent interactions with core ECM biomolecules, such as proteins and proteoglycans. Recently, these interactions have inspired us and others to develop synthetic biomaterials that can non-covalently regulate growth factor activity for tissue engineering applications. For example, biomaterials covalently or non-covalently modified with heparin glycosaminoglycans can augment growth factor release strategies. In addition, recent studies demonstrate that biomaterials modified with heparin-binding peptides can sequester cell-secreted heparin proteoglycans and, in turn, sequester growth factors and regulate stem cell behavior. Another set of studies show that modular versions of growth factor molecules can be designed to interact with specific components of natural and synthetic ECMs, including collagen and hydroxyapatite. In addition, layer-by-layer assemblies of GAGs and other natural polyelectrolytes retain growth factors at a cell-material interface via specific non-covalent interactions. This review will detail the various bioinspired strategies being used to non-covalently localize growth factor activity within biomaterials, and will highlight in vivo examples of the efficacy of these materials to promote tissue regeneration.  相似文献   

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The structure of tissue plays a critical role in its function and therefore a great deal of attention has been focused on engineering native tissue‐like constructs for tissue engineering applications. Transfer printing of cell layers is a new technology that allows controlled transfer of cell layers cultured on smart substrates with defined shape and size onto tissue‐specific defect sites. Here, the temperature‐responsive swelling‐deswelling of the hydrogels with groove patterns and their versatile and simple use as a template to harvest cell layers with anisotropic extracellular matrix assembly is reported. The hydrogels with a cell‐interactive peptide and anisotropic groove patterns are obtained via enzymatic polymerization. The results show that the cell layer with patterns can be easily transferred to new substrates by lowering the temperature. In addition, multiple cell layers are stacked on the new substrate in a hierarchical manner and the cell layer is easily transplanted onto a subcutaneous region. These results indicate that the evaluated hydrogel can be used as a novel substrate for transfer printing of artificial tissue constructs with controlled structural integrity, which may hold potential to engineer tissue that can closely mimic native tissue architecture.  相似文献   

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Injectable materials often have shortcomings in mechanical and drug‐eluting properties that are attributable to their high water contents. A water‐free, liquid four‐armed PEG modified with dopamine end groups is described which changes from liquid to elastic solid by reaction with a small volume of Fe3+ solution. The elastic modulus and degradation times increase with increasing Fe3+ concentrations. Both the free base and the water‐soluble form of lidocaine can be dissolved in the PEG4‐dopamine and released in a sustained manner from the cross‐linked matrix. PEG4‐dopamine is retained in the subcutaneous space in vivo for up to 3 weeks with minimal inflammation. This material's tailorable mechanical properties, biocompatibility, ability to incorporate hydrophilic and hydrophobic drugs and release them slowly are desirable traits for drug delivery and other biomedical applications.  相似文献   

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Tough, dense polyelectrolyte complexes (PECs) with well‐defined cross‐sections are prepared using a laboratory extruder and plasticizing the complexes with salt water. Stoichiometric starting materials yield stoichiometric complexes of poly(diallyldimethylammonium) (PDADMA) and poly(styrene sulfonate) (PSS). As an example of this enabling technology, macroscopic tubes of PEC are produced. Microscopy images of cross‐sections of rods, tape, and tubes show a pore volume of less than 10% in the bulk of the extruded complex and fully dense material towards the surface, where the shear is greatest. Thermal gravimetric analysis reveals the expected salt content for PECs doped with NaCl, and a lack of salt for PECs rinsed in water. The fact that doped PECs are transparent suggests they are supersaturated with salt. Residual stress following extrusion is relieved by exposure to solutions of NaCl. Stress relaxation experiments show decreasing equilibrium moduli as a function of increasing salt doping, consistent with prior results on multilayers of the same polymers.  相似文献   

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