Anisometric Microstructures to Determine Minimal Critical Physical Cues Required for Neurite Alignment

Advanced Healthcare Materials, vol. 10, pp. e2100874

Abstract

In nerve regeneration, scaffolds play an important role in providing an artificial extracellular matrix with architectural, mechanical, and biochemical cues to bridge the site of injury. Directed nerve growth is a crucial aspect of nerve repair, often introduced by engineered scaffolds imparting linear tracks. The influence of physical cues, determined by well-defined architectures, has been mainly studied for implantable scaffolds and is usually limited to continuous guiding features. In this report, the potential of short anisometric microelements in inducing aligned neurite extension, their dimensions, and the role of vertical and horizontal distances between them, is investigated. This provides crucial information to create efficient injectable 3D materials with discontinuous, in situ magnetically oriented microstructures, like the Anisogel. By designing and fabricating periodic, anisometric, discreet guidance cues in a high-throughput 2D in vitro platform using two-photon lithography techniques, the authors are able to decipher the minimal guidance cues required for directed nerve growth along the major axis of the microelements. These features determine whether axons grow unidirectionally or cross paths via the open spaces between the elements, which is vital for the design of injectable Anisogels for enhanced nerve repair.

Authors 6

1. Sitara Vedaraman Aachen Institute for Technical and Macromolecular Chemistry DWI - Leibniz Institute for Interactive Materials

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI‐Leibniz Institute for Interactive Materials Forckenbeckstrasse 50 Aachen 52074 Germany

   Institute for Technical and Macromolecular Chemistry RWTH Aachen Worringerweg 1–2 Aachen 52074 Germany

   DWI-Leibniz Institute for Interactive Materials, Forckenbeckstrasse 50, Aachen, 52074 Germany

2. Amaury Perez-Tirado Aachen DWI - Leibniz Institute for Interactive Materials

   DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI‐Leibniz Institute for Interactive Materials Forckenbeckstrasse 50 Aachen 52074 Germany

   DWI-Leibniz Institute for Interactive Materials, Forckenbeckstrasse 50, Aachen, 52074 Germany

3. Tamás Haraszti Aachen Institute for Technical and Macromolecular Chemistry DWI - Leibniz Institute for Interactive Materials

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI‐Leibniz Institute for Interactive Materials Forckenbeckstrasse 50 Aachen 52074 Germany

   Institute for Technical and Macromolecular Chemistry RWTH Aachen Worringerweg 1–2 Aachen 52074 Germany

   DWI-Leibniz Institute for Interactive Materials, Forckenbeckstrasse 50, Aachen, 52074 Germany

4. José Gerardo‐Nava Aachen DWI - Leibniz Institute for Interactive Materials

   DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI‐Leibniz Institute for Interactive Materials Forckenbeckstrasse 50 Aachen 52074 Germany

   DWI-Leibniz Institute for Interactive Materials, Forckenbeckstrasse 50, Aachen, 52074 Germany

5. Akihiro Nishiguchi

   National Institute for Materials Science

   Affiliation as printed

   Biomaterials Field Research Center for Functional Materials National Institute for Materials Science Tsukuba 305‐0044 Japan

   Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, 305-0044 Japan

6. Laura De Laporte corresponding Aachen Institute for Technical and Macromolecular Chemistry Institute of Applied Medical Engineering Department of Advanced Materials for Biomedicine DWI - Leibniz Institute for Interactive Materials

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI‐Leibniz Institute for Interactive Materials Forckenbeckstrasse 50 Aachen 52074 Germany

   Institute for Technical and Macromolecular Chemistry RWTH Aachen Worringerweg 1–2 Aachen 52074 Germany

   Institute of Applied Medical Engineering Department of Advanced Materials for Biomedicine RWTH University Forckenbeckstraße 55 Aachen 52074 Germany

   DWI-Leibniz Institute for Interactive Materials, Forckenbeckstrasse 50, Aachen, 52074 Germany