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1.
    
Cells embedded in the extracellular matrix of tissues play a critical role in maintaining homeostasis while promoting integration and regeneration following damage or disease. Emerging engineered biomaterials utilize decellularized extracellular matrix as a tissue-specific support structure; however, many dense, structured biomaterials unfortunately demonstrate limited formability, fail to promote cell migration, and result in limited tissue repair. Here, a reinforced composite material of densely packed acellular extracellular matrix microparticles in a hydrogel, termed tissue clay, that can be molded and crosslinked to mimic native tissue architecture is developed. Hyaluronic acid-based hydrogels are utilized, amorphously packed with acellular cartilage tissue particulated to ≈125–250 microns in diameter and defined a percolation threshold of 0.57 (v/v) beyond which the compressive modulus exceeded 300 kPa. Remarkably, primary chondrocytes recellularize particles within 48 h, a process driven by chemotaxis, exhibit distributed cellularity in large engineered composites, and express genes consistent with native cartilage repair. In addition, broad utility of tissue clays through recellularization and persistence of muscle, skin, and cartilage composites in an in vivo mouse model is demonstrated. The findings suggest optimal material architectures to balance concurrent demands for large-scale mechanical properties while also supporting recellularization and integration of dense musculoskeletal and connective tissues.  相似文献   

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Cells in vivo are surrounded by fibrous extracellular matrix (ECM), which can mediate the propagation of active cellular forces through stressed fiber bundles and regulate various biological processes. However, the mechanisms for multi-cellular organization and collective dynamics induced by cell-ECM mechanical couplings, which are crucial for the development of novel ECM-based biomaterial for cell manipulation and biomechanical applications, remain poorly understood. Herein, the authors design an in vitro quasi-3D experimental system and demonstrate a transition between spreading and aggregating in collective organizational behaviors of discrete multi-cellular systems, induced by engineered ECM-cell mechanical coupling, with the observed phenomena and underlying mechanisms differing fundamentally from those of cell monolayers. During the process of collective cell organization, the collagen substrate undergoes reconstruction into a dense fiber network structure, which is correlated with local cellular density and consistent with observed enhanced cells' motility; and the weakening of fiber bundle formation within the hydrogel reduces cells’ movement. Moreover, cells can respond to the curvature and shape of the original cell population and form different aggregation patterns. These results elucidate important physical factors involved in collective cell organization and provide important references for potential applications of biomaterials in new therapies and tissue engineering.  相似文献   

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Hydrogels are commonly used as engineered extracellular matrix (ECM) mimics in applications ranging from tissue engineering to in vitro disease models. Ideal mechanisms used to crosslink ECM‐mimicking hydrogels do not interfere with the biology of the system. However, most common hydrogel crosslinking chemistries exhibit some form of crossreactivity. The field of bioorthogonal chemistry has arisen to address the need for highly specific and robust reactions in biological contexts. Accordingly, bioorthogonal crosslinking strategies are incorporated into hydrogel design, allowing for gentle and efficient encapsulation of cells in various hydrogel materials. Furthermore, the selective nature of bioorthogonal chemistries can permit dynamic modification of hydrogel materials in the presence of live cells and other biomolecules to alter matrix mechanical properties and biochemistry on demand. This review provides an overview of bioorthogonal strategies used to prepare cell‐encapsulating hydrogels and highlights the potential applications of bioorthogonal chemistries in the design of dynamic engineered ECMs.  相似文献   

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In recent decades, collagen is one of the most versatile biomaterials used in biomedical applications, mostly due to its biomimetic and structural composition in the extracellular matrix (ECM). Several attempts are proposed for designing innovative collagen‐based biomaterials and applying them in tissue regeneration. The regeneration of different tissues is prompted by different types and diverse physical forms of collagen‐based biomaterials prepared by various methods. Based on such concepts, the source, structure, and classification of collagen are briefly introduced in this review. Here, the commonly used physical forms and modification methods of collagen‐based biomaterials are reviewed, including hydrogels, scaffolds, and microspheres, followed by their applications in the regeneration of tissues and organs. Important proof‐of‐concept examples are described to demonstrate the outcomes on material characteristics, cellular reactions, and tissue regeneration. A concise assessment of the limitations that still exist and the developing trends in the future of collagen‐based biomaterials are put forward.  相似文献   

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Using an innovative, tissue‐independent approach to decellularized tissue processing and biomaterial fabrication, the development of a series of “tissue papers” derived from native porcine tissues/organs (heart, kidney, liver, muscle), native bovine tissue/organ (ovary and uterus), and purified bovine Achilles tendon collagen as a control from decellularized extracellular matrix particle ink suspensions cast into molds is described. Each tissue paper type has distinct microstructural characteristics as well as physical and mechanical properties, is capable of absorbing up to 300% of its own weight in liquid, and remains mechanically robust (E = 1–18 MPa) when hydrated; permitting it to be cut, rolled, folded, and sutured, as needed. In vitro characterization with human mesenchymal stem cells reveals that all tissue paper types support cell adhesion, viability, and proliferation over four weeks. Ovarian tissue papers support mouse ovarian follicle adhesion, viability, and health in vitro, as well as support, and maintain the viability and hormonal function of nonhuman primate and human follicle‐containing, live ovarian cortical tissues ex vivo for eight weeks postmortem. “Tissue papers” can be further augmented with additional synthetic and natural biomaterials, as well as integrated with recently developed, advanced 3D‐printable biomaterials, providing a versatile platform for future multi‐biomaterial construct manufacturing.  相似文献   

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Restoring extracellular matrix (ECM) with supportive and osteoinductive abilities is of great significance for bone tissue regeneration. Current approaches involving cell‐based scaffolds or nanoparticle‐modified biomimic‐ECM have been met with additional biosafety concerns. Herein, the natural biomineralization process is first analyzed and is found that mesenchymal stem cells‐derived extracellular vesicles (EVs) from early and late stages of osteoinduction play different roles during the mineralization process. The functional EVs hierarchically with blood‐derived autohydrogel (AH) are then incorporated to form an osteoinductive biomimetic extracellular matrix (BECM). The alkaline phosphatase‐rich EVs are released from the outer layers to induce osteoblast differentiation during early stages. Thereafter, as the degradation of AH occurred, calcium/phosphorus (Ca/P)‐rich EVs are liberated to promote the nucleation of extracellular mineral crystals. Additionally, BECM contains considerable collagen fibrils that provide additional nucleation sites for crystallites deposition, thus reaching self‐mineralization in situ. In conclusion, this research provides a promising, versatile mineralization‐instructive platform to tackle the challenges faced in bone‐tissue engineering.  相似文献   

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Biomimetic scaffolds generally aim at structurally and compositionally imitating native tissue, thus providing a supportive microenvironment to the transplanted or recruited cells in the tissue. Native decellularized porcine extracellular matrix (ECM) is becoming the ultimate bioactive material for the regeneration of different organs. Particularly for cardiac regeneration, ECM is studied as a patch and injectable scaffolds, which improve cardiac function, yet lack reproducibility and are difficult to control or fine‐tune for the desired properties, like most natural materials. Seeking to harness the natural advantages of ECM in a reproducible, scalable, and controllable scaffold, for the first time, a matrix that is produced from whole decellularized porcine cardiac ECM using electrospinning technology, is developed. This unique electrospun cardiac ECM mat preserves the composition of ECM, self‐assembles into the same microstructure of cardiac ECM ,and ,above all, preserves key cardiac mechanical properties. It supports cell growth and function, and demonstrates biocompatibility in vitro and in vivo. Importantly, this work reveals the great potential of electrospun ECM‐based platforms for a wide span of biomedical applications, thus offering the possibility to produce complex natural materials as tailor‐made, well‐defined structures.  相似文献   

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Tissue‐derived decellularized extracellular matrices (dECM) have gradually become the gold standard of scaffolds for tissue engineering, owing to their close mirroring of the intricate composition, architecture, and topology of the native extracellular matrix (ECM). Intriguingly, further manipulation of these acellular tissues through various processing techniques has been demonstrated to be an effective strategy to control their characteristics and impart them with ample valuable new traits, thereby expanding their applicability to a significantly wider spectrum of research and translational applications. Herein, state‐of‐the‐art processed dECM platforms and their potential applications are focused on. The ECM characteristics that make it so appealing for tissue engineering are presented, followed by a concise discussion on the main considerations for choosing a dECM source for such applications. The key methodologies for dECM processing, including hydrogel production, bioprinting, electrospinning, and production of porous scaffolds, microcarriers, and microcapsules, as well as their inherent advantages and challenges, are introduced. To demonstrate the use of processed dECM platforms for tissue engineering, selected in vivo and in vitro applications recently developed utilizing these platforms are highlighted. Finally, concluding remarks and a prospective outlook for future developments and improvements in the field of processed dECM‐based devices are given.  相似文献   

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The therapeutic benefits of mesenchymal stromal cell (MSC) transplantation are attributed to their secreted factors, including extracellular vesicles (EVs) and soluble factors. The potential of employing the MSC secretome as an alternative acellular approach to cell therapy is being investigated in various tissue injury indications, but EVs administered via bolus injections are rapidly sequestered and cleared. However, biomaterials offer delivery platforms to enhance EV retention rates and healing efficacy. This review highlights the mechanisms underpinning the therapeutic effects of MSC‐EVs and soluble factors as effectors of immunomodulation and tissue regeneration, conferred primarily via their nucleic acid and protein contents. Discussed is how manipulating the cell culture microenvironment or genetic modification of MSCs can further augment the potency of their secretions. The most recent advances in the development of EV‐functionalized biomaterials that mediate enhanced angiogenesis and cell survival, while attenuating inflammation and fibrosis, are presented. Finally, some technical challenges to be considered for the clinical translation of biomaterials carrying MSC‐secreted bioactive cargo are discussed.  相似文献   

11.
Native tissues are endowed with a highly organized nanofibrous extracellular matrix (ECM) that directs cellular distribution and function. The objective of this study is to create a purely natural, uniform, and highly aligned nano­fibrous ECM scaffold for potential tissue engineering applications. Synthetic nanogratings (130 nm in depth) are used to direct the growth of human dermal fibroblasts for up to 8 weeks, resulting in a uniform 70 μm‐thick fibroblast cell sheet with highly aligned cells and ECM nanofibers. A natural ECM scaffold with uniformly aligned nanofibers of 78 ± 9 nm in diameter is generated after removing the cellular components from the fibroblast sheet. The elastic modulus of the scaffold is well maintained after the decellularization process because of the preservation of elastin fibers. Reseeding human mesenchymal stem cells (hMSCs) shows the excellent capacity of the scaffold in directing and supporting cell alignment and proliferation along the underlying fibers. The scaffold's biocompatibility is further examined by an in vitro inflammation assay with seeded macrophages. The aligned ECM scaffold induces a significantly lower immune response compared to its unaligned counterpart, as detected by the pro‐inflammatory cytokines secreted from macrophages. The aligned nanofibrous ECM scaffold holds great potential in engineering organized tissues.  相似文献   

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Synapse formation in complex neuronal network is a pivotal process for normal functioning of nervous system. Although intense research has been conducted, how neurons and axons are guided toward the target remains largely unclear. In traditional opinions, axons are directed through chemotaxis, while recently mechanotaxis has been brought up as a potential complementary mechanism, as it can provide delicately controlled signals in addition to the random diffusive chemical cues. To further explore the path-finding mechanism, a quasi-3D in vitro model for neuronal cells is constructed by integrating hydrogel collagen I as extracellular matrix (ECM), and primary mouse cortical neurons and PC12 cells are tested. It is strikingly found out that axons and neuronal cells can be precisely guided toward target neurites via ECM. By developing a label-free traction force microscopy technique, the force networks among neurons are presented, validating that the fibrous matrix-transmitted paratensile signals can assist the axon pathfinding. This precise axon guidance is related to the activation of mechanosensitive ion channels, calcium signaling, and probably the following F-actin assembly. This mechanism can potentially assist developing clinical applications and designing biomaterials in near future.  相似文献   

14.
郑念 《数字通信》2012,39(6):73-75
分析了当前移动软交换组网中各种容灾备份方法,说明了主备和互备2种容灾方式的网络结构、工作方式及存在的隐患。结合移动核心网容灾备份发展趋势,重点介绍MSC pool容灾方式的优势,并结合重庆联通MSC pool的组网方式,说明了MSC pool的实现方式、优缺点等问题。  相似文献   

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Hydrogel models of metastasis traditionally focus on the invasion of cancer cells; however, other cells in the tumor microenvironment that are associated with metastasis also have the ability to migrate. Macrophage phenotype plays a key role in the tumor microenvironment, yet understanding their migration within tunable 3D in vitro models has been limited. To gain a greater understanding of macrophage invasive behavior, stable and transparent oxime-crosslinked cryogels comprised of click-crosslinked gelatin-oxyamine and hyaluronan-aldehyde (GELox-HAa) are synthesized. Fibronectin-derived, oxyamine-modified PHSRN-RGDSP peptides are incorporated to further mimic the tumor extracellular matrix without impacting cryogel mechanics. It is found that primary human macrophages migrate to a greater depth in cryogels with greater porosity and pore size. To better understand the mechanism of migration, cells are treated with either inhibitors of matrix metalloproteinases (MMPs) or rho-associated protein kinase (ROCK) and a predominantly MMP-mediated mechanism of invasion is found. Macrophage polarization studies reveal that anti-inflammatory, interleukin-4/13 (IL4/IL13)-treated macrophages migrate through cryogels to a greater extent than pro-inflammatory, interferon-gamma/lipopolysaccharide (IFNγ/LPS)-treated cells. Interestingly, polarized macrophages move through cryogels using a combination of amoeboid and mesenchymal migration. These findings of macrophage invasion in this cryogel platform set the stage for their further study in a biomimetic tumor microenvironment.  相似文献   

16.
王笛 《移动通信》2011,35(3):111-116
文章主要介绍了在株洲TD—SCDMA网络进行MSC Pool改造过程中发现的相关f引题及其分析与解决,如改造后中终端无法从GSM重选回TD—SCDMA网络、RNC与MSC Server挂接变更导致统计指标数据下降等,为MSC Pool技术改造积累经验。  相似文献   

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The directed differentiation of human pluripotent stem cells (hPSCs) into defined populations has advanced regenerative medicine, especially for Parkinson's disease where clinical trials are underway. Despite this, tumorigenic risks associated with incompletely patterned and/or quiescent proliferative cells within grafts remain. Addressing this, donor stem cells carrying the suicide gene, thymidine kinase (activated by the prodrug ganciclovir, GCV), are employed to enable the programmed ablation of proliferative cells within neural grafts. However, coinciding the short half-life of GCV with the short S-phase of neural progenitors is a key challenge. To overcome this, a smart hydrogel delivery matrix is fabricatedto prolong GCV presentation. Following matrix embedment, GCV retains its functionality, demonstrated by ablation of hPSCs and proliferating neural progenitors in vitro. A prolonged GCV release is measured by mass spectrometry following the injection of a GCV-functionalized hydrogel into mouse brains. Compared to suboptimal, daily systemic GCV injections, the intracerebral delivery of the functionalized hydrogel, as a “one-off treatment”, reduce proliferative cells in both hPSC-derived teratomas and neural grafts, without affecting the graft's functional unit (i.e., neurons). It is demonstrated that a functionalized biomaterial can enhance prodrug delivery and address safety concerns associated with the use of hPSCs for brain repair.  相似文献   

18.
通过大量现有网络统计数据的分析,对合理分配话务、简化网络扩容、优化网络资源、提升设备利用率、保证网络安全等MSCinPool组网的优势进行了验证,最后通过对实际MscinPool网络的分析观察给出了MSCPool组网规划的相关建议。  相似文献   

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本文讨论了MSC池组网的位置更新。相对传统组网,池组网因为采用共享核心网的组网策略,消除了池内的跨局位置更新,提高了MSC Server(移动交换中心服务器)的设备利用率。  相似文献   

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