Cell-Instructive Alginate Hydrogels Targeting RhoA
| Autor: | Emma Cavalli, Florian A. Formica, Marcy Zenobi-Wong, Nicolas Broguiere |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
RHOA Botulinum Toxins Alginates Cell Biomedical Engineering Pharmaceutical Science Bioengineering Biocompatible Materials 02 engineering and technology Matrix (biology) 03 medical and health sciences Mice Chondrocytes medicine Animals Cytoskeleton Pharmacology ADP Ribose Transferases biology Tissue Scaffolds Chemistry Regeneration (biology) Cartilage Organic Chemistry Hydrogels Cell Dedifferentiation 021001 nanoscience & nanotechnology Chondrogenesis Enzymes Immobilized In vitro Cell biology 030104 developmental biology medicine.anatomical_structure biology.protein 0210 nano-technology rhoA GTP-Binding Protein Biomarkers Biotechnology |
| Zdroj: | Bioconjugate Chemistry, 29 (9) |
| ISSN: | 1520-4812 1043-1802 |
| Popis: | Cellular processes involve dynamic rearrangement of the cytoskeleton. The GTPase RhoA plays a fundamental role in controlling cytoskeletal architecture. The phenotypic stability of chondrocytes is enhanced through inhibition of RhoA, whereas RhoA activation leads to dedifferentiation. We hypothesized that local inhibition of this pathway could induce chondrogenesis and cartilage regeneration. In this study, a novel alginate-derived hydrogel system was developed for sustained RhoA targeting. Specifically, an engineered variant of C. botulinum C3 transferase, a potent RhoA inhibitor, was immobilized onto a hydrogel to achieve sustained release and enzymatic activity. Chondrocytes encapsulated within this fully biocompatible, mechanically stable scaffold produced a stable collagen type II-rich matrix in vitro which matured over a six-week period. Samples were implanted subcutaneously in mice, and similar production of a collagen type II-rich matrix was observed. The intrinsically versatile system has the potential to treat a number of clinical disorders, including osteoarthritis, linked with RhoA dysregulation. Bioconjugate Chemistry, 29 (9) ISSN:1043-1802 ISSN:1520-4812 |
| Databáze: | OpenAIRE |
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