Wiens, Matthias; Niem, Thomas; Elkhooly, Tarek A.; Steffen, Renate; Neumann, Sebastian; Schloßmacher, Ute; Müller, Werner E. G.
doi: 10.1039/c3tb20325epmid: 32260923
A P(UDMA-co-MPS) copolymer was surface-functionalized through the polycondensation activity of the enzyme silicatein. The resulting biosilica coating significantly enhanced mineralization of osteoblastic cells, thereby revealing its osteogenic potential. Consequently, the functionalized copolymer may be explored as an alternative to conventionally used acrylics in applications where stable bone–material interfaces are required.
Wang, Ya; Jia, Hui-Zhen; Han, Kai; Zhuo, Ren-Xi; Zhang, Xian-Zheng
doi: 10.1039/c3tb20509fpmid: 32260924
Cancer is considered to be the leading factor which threatens human lives nowadays, and 90% of cancer-related deaths are attributed to the metastasis of cancer. Thus an effective and simultaneous separation and therapeutic method for circulating tumor cells is crucial for improving the diagnosis, prognosis, and treatment of cancer. Here, we report the design of theranostic magnetic nanoparticles conjugated with the targeting peptide SP94 and the anticancer drug doxorubicin (DOX) (symbolized as Fe3O4–DOX/SP94) for the targeted isolation of the human hepatocellular carcinoma cell line (HepG2), followed by the in situ chemotherapy of cancer cells upon capture. It was found that the capture efficiencies of 400 μg Fe3O4–DOX/SP94 for HepG2 cells and human embryonic kidney transformed 293 cells (293T) were around 75% and 5% respectively after 15 min incubation. Furthermore, it is worth mentioning that DOX was covalently conjugated via pH-sensitive hydrazone bonds, and the in vitro release studies demonstrated that DOX was released much faster at pH 5.0 than at pH 7.4. According to the in vitro cytotoxicity assays, significantly reduced cell viability was observed in HepG2 cells when the concentration of Fe3O4–DOX/SP94 nanoparticles was 300 μg mL−1. Such a rapid and facile approach has considerable potential for the targeted capture as well as effective chemotherapy of circulating tumor cells, in an attempt to improve the curative effects against metastatic diseases.
Marin, Luminita; Stoica, Iuliana; Mares, Mihai; Dinu, Valentina; Simionescu, Bogdan C.; Barboiu, Mihail
doi: 10.1039/c3tb20558dpmid: 32260925
Vanillin–chitosan biodynamers have been prepared and structure–morphology correlations revealed the pathway of progressive incorporation of the aldehyde onto chitosan backbones. Such dynamic biopolymers or biodynamers, generated from reversibly interacting components, offer the possibility to address the dynamic covalent behaviour of the reversible imine-bond formation/hydrolysis equilibria between vanillin and chitosan polymeric backbones. The reaction takes place with very low conversion in acidic aqueous solutions (7–12%), but the imine bond formation is amazingly improved (∼80%) when the reaction takes place while solution–solid state transition and solid state phase-organization events occur. The chitosan–vanillin biopolymeric films described here present interesting Candida albicans antifungal activity compared with other common bacterial strands, which suggests the implementation of these biocompatible materials as thin layer protecting systems for medical devices.
de Araújo Farias, Virgínea; López-Peñalver, Jesús J.; Sirés-Campos, Julia; López-Ramón, María Victoria; Moreno-Castilla, Carlos; Oliver, Francisco Javier; Ruiz de Almodóvar, José Mariano
doi: 10.1039/c3tb20305kpmid: 32260926
Messager, Léa; Portecop, Naïra; Hachet, Emilie; Lapeyre, Véronique; Pignot-Paintrand, Isabelle; Catargi, Bogdan; Auzély-Velty, Rachel; Ravaine, Valérie
doi: 10.1039/c3tb20300jpmid: 32260927
We present the preparation of nanogels made of hyaluronic acid (HA) with a well-controlled structure. To this end, HA precursors with polymerizable methacrylate groups (HA-MA) were confined within water-in-oil nanoemulsion droplets as nanoreactors and further photopolymerized under UV. Particular attention was paid to the preparation of a stable nanoemulsion template with a homogeneous droplet size. Upon UV irradiation of the emulsion containing HA-MA, crosslinked HA-MA particles with a well-defined size were obtained. Moreover, by varying the photopolymerization conditions, i.e. the number of received photons, we could control the conversion rate of the polymerization, as proved by 1H-NMR. Nanogels with controlled cross-linking densities were thus obtained. Not only could their crosslinking densities be controlled by the number of incident photons, but also by the degree of methacrylation (DM) of HA-MA derivatives. In addition, the swelling properties of the nanogels depended on external factors, showing their pH and ionic strength responsiveness. We show that these structures were highly biocompatible, stable under storage and enzymatically biodegradable, which opens the route for their application as drug delivery systems. Finally, insulin was loaded in the nanogels and its pH-dependent release was demonstrated. This versatile method of nanogel preparation, which can be applied to every type of hydrophilic precursor, offers a potential synthetic route to design other types of fully biocompatible drug delivery systems.
Zhou, Yinghong; Wu, Chengtie; Zhang, Xufang; Han, Pingping; Xiao, Yin
doi: 10.1039/c3tb20445fpmid: 32260928
Periodontitis results from the destructive inflammatory reaction of the host elicited by a bacterial biofilm adhering to the tooth surface and if left untreated, may lead to the loss of the teeth and the surrounding tissues, including the alveolar bone. Cementum is a specialized calcified tissue covering the tooth root and an essential part of the periodontium which enables the attachment of the periodontal ligament to the root and the surrounding alveolar bone. Periodontal ligament cells (PDLCs) represent a promising cell source for periodontal tissue engineering. Since cementogenesis is the critical event for the regeneration of periodontal tissues, this study examined whether inorganic stimuli derived from bioactive bredigite (Ca7MgSi4O16) bioceramics could stimulate the proliferation and cementogenic differentiation of PDLCs, and further investigated the involvement of the Wnt/β-catenin signalling pathway during this process via analysing gene/protein expression of PDLCs which interacted with bredigite extracts. Our results showed that the ionic products from bredigite powder extracts led to significantly enhanced proliferation and cementogenic differentiation, including mineralization–nodule formation, ALP activity and a series of bone/cementum-related gene/protein expression (ALP, OPN, OCN, BSP, CAP and CEMP1) of PDLCs in a concentration dependent manner. Furthermore, the addition of cardamonin, a Wnt/β-catenin signalling inhibitor, reduced the pro-cementogenesis effect of the bredigite extracts, indicating the involvement of the Wnt/β-catenin signalling pathway in the cementogenesis of PDLCs induced by bredigite extracts. The present study suggests that an entirely inorganic stimulus with a specific composition of bredigite bioceramics possesses the capacity to trigger the activation of the Wnt/β-catenin signalling pathway, leading to stimulated differentiation of PDLCs toward a cementogenic lineage. The results indicate the therapeutic potential of bredigite ceramics in periodontal tissue engineering application.
Chong, E. Y. W.; Ng, C. Y. P.; Choi, V. W. Y.; Yan, L.; Yang, Y.; Zhang, W. J.; Yeung, K. W. K.; Chen, X. F.; Yu, K. N.
doi: 10.1039/c3tb20114gpmid: 32260929
Efficient delivery of biomolecules to cells is of great importance in biology and medicine. To achieve this, we designed a novel type of densely packed diamond nanocone array to conveniently transport molecules to the cytoplasm of a great number of cells. The nanocone array was fabricated by depositing a thin layer of diamond film on a silicon substrate followed by bias-assisted reactive ion etching. The height of the diamond nanocones varied from 200 nm to 1 μm with tip radii of approximately 10 nm. Our fluorescein and propidium iodide staining results clearly demonstrated that dramatically enhanced delivery of fluorescein into cells was realized without leading to noticeable cell death with the aid of nanocone treatment. As a test case of the drug delivery application of the device, MC-3T3 cells in differentiation medium were applied to the nanocone array for enhanced intracellular delivery of the medium. This was confirmed by the fact that nanocone treated cells experienced much higher differentiation ability at an early stage in comparison with untreated cells. Overall, the results indicate that the diamond nanocone array provides a very simple but yet very effective approach to achieve delivery of molecules to a large number of cells.
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We have investigated the capacity of activated carbon cloth to support the growth and differentiation of human mesenchymal umbilical-cord stromal stem cells. Our results demonstrate that this scaffold provides suitable conditions for the development of cell-derived matrix proteins and facilitates the growth of undifferentiated stem cells with the ability to induce osteogenic and chondrogenic differentiation. Immunoflourescence staining revealed extensive expression of collagen in all the samples, and collagen type II and osteopontin within the samples cultivated in specific differentiation-inducing media. Cell growth and the formation of natural collagen, calcium–magnesium carbonate and hydroxyapatite crystals, together with the self-assemblage of collagen to produce suprafibrillar arrangements of fibrils all occur simultaneously and can be studied together ex vivo under physiological conditions. Furthermore, the spontaneous differentiation of stem cells cultured on activated carbon cloth with no osteogenic supplements opens up new possibilities for bone-tumour engineering and treatment of traumatic and degenerative bone diseases.