Aufbau von gradierten, chiralen und stimuli-responsiven Nanokomposit-Hydrogelen mittels 3D-Bioprinting als multifunktionale Biomaterialien zur Untersuchung von Zell/Biomaterial-Wechselwirkungen

• Antragstellerin: Dr. Nermin Seda Kehr
• Fachliche Zuordnung: Biomaterialien ; Herstellung und Eigenschaften von Funktionsmaterialien
• Förderung: Förderung von 2015 bis 2022
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 268394705

• Erstellungsjahr: 2022

Zusammenfassung der Projektergebnisse

Our research results demontrated that (a) cells distinguishes between the enantiomers on the NMs surfaces; thus, cells’ adhesion, proliferation, and migration were influenced by chirality on the NMs surfaces and within the 3D network of the NC hydrogels (chirality-dependent cell adhesion and migration). (b) chirality-dependent cell adhesion was directly correlated with differentiated adsorption behavior of proteins on chiral surfaces. The specific stereoselective interactions between proteins and chiral surfaces resulted in new stereochemistries on the chiral surfaces, which in turn influenced cell affinity. (c) step-gradient or triphasic NC hydrogels can be prepared using 3D printing techniques in XY and XZ plane. So we were able to direct the migration of fibroblast cells and the osteogenic differentiation of hBM MSCs towards areas in a 3D hydrogel network with higher concentrations of functional NMs or with biomolecules delivery from the pH-responsive NMs. The controlled migration and subsequent differentiation of stem cells is important to avoid pathological conditions such as cancer and metastasis. (d) we can prepare acidic-pH-responsive NMs and 3D NC hydrogels for controlled surface-mediated high-dosage drug delivery to malignant cells and spare healthy cells (proof of principle for pH-responsive local drug delivery). The acidic environment of cancer cells triggered the release of higher amounts of anticancer drugs from the pH-responsive NMs than did the environment of healthy cells, indicating the potential application of our system in cancer treatment. (e) we can prepare bifunctional NMs that reduce bacterial bioluminescence and biofilm formation of pathogenic bacteria while enhancing the viability of eukaryotic cells on biomaterial surfaces which is crucial for wound healing and wound dressing development. (f) we can prepare drug loaded perfluorcarbon-based NMs and injectable hydrogels as new oxygen and drug co-releasing biomaterials that reduce cancer cell viability while promoting the proliferation of healthy cells, which is important for minimally-invasive cancer treatment. Potential applications of our results include chirality-dependent cell enrichment, cell-cell separation and migration, local drug delivery, minimally invasive cancer treatment, and the generation of wound healing and/or wound dressing materials.

Projektbezogene Publikationen (Auswahl)

• “3D Bioprinting of Triphasic Nanocomposite Hydrogels and Scaffolds for Cell Adhesion and Migration”, Biofabrication, 2019, 11, 035022
  A. Motealleh, P. Dorri, A. H. Schäfer, and N. S. Kehr
  
• “3D Printing of Step-Gradient Nanocomposite Hydrogels for Controlled Cell Migration”, Biofabrication, 2019, 11, 045015
  A. Motealleh, B. Celebi-Saltik, N. Ermis, S. Nowak, A. Khademhosseini, and N. S. Kehr
  
• “Stimuli-responsive Local Drug Molecule Delivery to Adhered Cells in a 3D Nanocomposite Scaffold”, J. Mater. Chem. B., 2019, 7, 3716
  A. Motealleh, R. De Marco, and N. S. Kehr
  
• “Directed Vertical Cell Migration via Bifunctionalized Nanomaterials in 3D Step-gradient Nanocomposite Hydrogels”, Biomater. Sci., 2020, 8, 5628
  A. Motealleh, N. S. Kehr
  
• “Injectable Polymer/Nanomaterial Composites for the Fabrication of Three-Dimensional Biomaterial Scaffolds”, Biomed. Mater, 2020, 15, 045021
  A. Motealleh, P. Dorri, N. S. Kehr
  
• “Recent Advances in Injectable Hydrogels for Controlled and Local Drug Delivery”, Adv. Healthcare Mater. 2021, 2001341
  F. Rizzo, N. S. Kehr
  
• “Step-gradient Composite Hydrogels for Local Drug Delivery and Directed Cell Migration”, Adv. NanoBiomed Res. 1, 2021, 2000114
  A. Motealleh, N. S. Kehr
  
• „3D Printed Step-gradient Composite Hydrogels for Directed Migration and Osteogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells”, Nano Select, 2021, 3, 411
  A. Motealleh, A. Schulten, N. S. Kehr
  
• „Functional Nanomaterials and 3D- Printable Nanocomposite Hydrogels for Enhanced Cell Proliferation and for the Reduction of Bacterial Biofilm Formation”, ACS Appl. Mater. Interfaces 2021, 13, 43755
  A. Motealleh, D. Kart, M. Czieborowski, N. S. Kehr
  
• „3D-Printable Oxygen- and Drug-carrying Nanocomposite Hydrogels for Enhanced Cell Viability”, Nanomaterials 2022, 12, 1304
  R. Kumar, N. S. Kehr