Periodic Reporting for period 4 - ANISOGEL (Injectable anisotropic microgel-in-hydrogel matrices for spinal cord repair)
Período documentado: 2019-09-01 hasta 2021-08-31
The newly developed minimal invasive material is termed ‚Anisogel‘. If you aim to enhance the regeneration of damaged spinal cord tissue, you need to come up with a new material concept. We use micrometer-sized building blocks and assemble them into 3D hierarchically organized structures. Anisogel consists of two gel components. Many, microscopically small, soft rod-shaped gels, incorporated with a low amount of magnetic nanoparticles, are the first component. Using a weak magnetic field, scientists can orient the gel rods, after which a very soft surrounding gel matrix is crosslinked, forming the structural guidance system. The gel rods, being stabilized by the gel matrix, maintain their orientation, even after removal of the magnetic field. Using cell culture experiments, we demonstrate that cells can easily migrate through this gel matrix, and that nerve cells and fibroblasts orient along the paths provided by this guidance system. A low amount of one percent gel rods inside the entire Anisogel volume is proven to be sufficient to induce linear nerve growth. The material is the first injectable biomaterial, which assembles into a controlled oriented structure after injection and provides a functional guidance system for cells.
Cell culture experiments revealed that cells and nerves feel the physical and mechanical anisotropy of the Anisogel, resulting in unidirectional growth. Only a minimal amount of rod-shaped guiding elements was required, all the way down to 1 vol% in the case of nerve cells. This work was recently published in the journal Nano Letters (June 2017, front cover).
Later, the effect of biofunctional molecules attached to the microgels was investigated and demonstrated that introducing cell adhesiveness of the microgels enhanced fibroblast attachment and alignment. Interestingly, modifying the microgels with cell-adhesive peptides, such as RGD, reduced the need of the cells to produce their own extracellular proteins, as a significan reduction of fibronectin was observed. This shows that the microgels nicely mimicked the natural ECM proteins available for the cells to attach to. As the produced fibronectin is also aligned, a positive feedback is presented for the cells, where the natural proteins can over time take over the function of the degradable microgels.
Based on this work, one additional paper was published open access in Small (September 2017, front cover plus an additional video abstract (featured on the Wiley website and https://youtu.be/136xwXsLWGg)).
In the second half of Anisogel, we will study the effect of microgel dimensions and aspect ratios on the rate of magnetic orientation and directed cell growth inside the Anisogel. We will also further modify the microgels with different peptides to affect specific cell types. Further the function of the Anisogel will be investigated to grow aligned blood vessels (angiogenesis) and glial cells, present in the nervous system to insulate the nerves with myeling and enhance electrical nerve signaling.
The animal protocol will be submitted in 2017 to hopefully start testing the Anisogels in a rat contusion spinal cord injuyr model in 2018. These in vivo studies are crucial to proof the potential of the Anisogels for clinical therapies.