Metal-organic frameworks (MOFs) are promising platforms for the synthesis of nanoparticles for diverse medical applications. Their fundamental design principles allow for significant control of the framework architecture and pore chemistry, enabling directed functionalization for nanomedical applications. However, before applying novel nanomaterials to patients, it is imperative to understand their potential health risks. In this study, the nanosafety of different MOF nanoparticles is analyzed comprehensively for diverse medical applications. The authors first evaluate the effects of MOFs on human endothelial and mouse lung cells, which constitute a first line of defense upon systemic blood-mediated and local lung-specific applications of nanoparticles. Second, we validated these MOFs for multifunctional surface coatings of dental implants using human gingiva fibroblasts. Moreover, biocompatibility of MOFs is assessed for surface coating of nerve guidance tubes using human Schwann cells and rat dorsal root ganglion cultures. The main finding of this study is that the nanosafety and principal suitability of our MOF nanoparticles as novel agents for drug delivery and implant coatings strongly varies with the effector cell type. We conclude that it is therefore necessary to carefully evaluate the nanosafety of MOF nanomaterials with respect to their particular medical application and their interacting primary cell types, respectively.
Biodegradable materials play a crucial role in both material and medical sciences and are frequently used as a primary commodity for implants generation. Due to their material inherent properties, they are supposed to be entirely resorbed by the patients' body after fulfilling their task as a scaffold. This makes a second intervention (e.g. for implant removal) redundant and significantly enhances a patient's post-operative life quality. At the moment, materials for resorbable and biodegradable implants (e.g. polylactic acid or poly-caprolactone polymers) are still intensively studied. They are able to provide mandatory demands such as mechanical strength and attributes needed for high-quality implants. Implants, however, not only need to be made of adequate material, but must also to be personalized in order to meet the customers' needs. Combining three dimensional-printing and high-resolution imaging technologies a new age of implant production comes into sight. Three dimensional images (e.g. magnetic resonance imaging or computed tomography) of tissue defects can be utilized as digital blueprints for personalized implants. Modern additive manufacturing devices are able to use a variety of materials to fabricate custom parts within short periods of time. The combination of high-quality resorbable materials and personalized three dimensional-printing for the custom application will provide the patients with the best suitable and sustainable implants. In this study, we evaluated and compared four resorbable and three dimensional printable materials for their in vitro biocompatibility, in vitro rate of degradation, cell adherence and behavior on these materials as well as support of osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells. The tests were conducted with model constructs of 1 cm surface area fabricated with fused deposition modeling three dimensional-printing technology.
Cytocompatibility is essential for implant approval. However, initial in vitro screenings mainly include the quantity of adherent immortalized cells and cytotoxicity. Other vital parameters, such as cell migration and an in-depth understanding of the interaction between native tissue cells and implant surfaces, are rarely considered. We investigated different laser-fabricated spike structures using primary and immortalized cell lines of fibroblasts and osteoblasts and included quantification of the cell area, aspect ratio, and focal adhesions. Furthermore, we examined the three-dimensional cell interactions with spike topographies and developed a tailored migration assay for long-term monitoring on opaque materials. While fibroblasts and osteoblasts on small spikes retained their normal morphology, cells on medium and large spikes sank into the structures, affecting the composition of the cytoskeleton and thereby changing cell shape. Up to 14 days, migration appeared stronger on small spikes, probably as a consequence of adequate focal adhesion formation and an intact cytoskeleton, whereas human primary cells revealed differences in comparison to immortalized cell lines. The use of primary cells, analysis of the cell–implant structure interaction as well as cell migration might strengthen the evaluation of cytocompatibility and thereby improve the validity regarding the putative in vivo performance of implant material.
Metal‐organic frameworks (MOFs) are a promising platform for the synthesis of porous nanoparticles for diverse medical applications. Stefan Wuttke, Silke Meiners, and co‐workers comprehensively investigate the nanosafety and hence the general applicability of different MOF nanoparticles for distinct fields of medical applications (e.g. drug delivery or implant coatings) in article 1600818. Data presented here suggest the need to evaluate the nanosafety of each MOF nanomaterial with respect to their particular medical application.
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