Chapter 3 The central nervous system (CNS) consists of a dense network of cells leaving a smaller volume for the extracellular matrix (ECM) components (10‐20% for the brain unlike most other tissues (Cragg, 1979)). The reaction of the nervous tissue to any injury leading to scar tissue formation acts as a barrier for regeneration in the CNS, while it supports regeneration in the peripheral nervous system (PNS). By mimicking several unique characteristics of the natural environment of cells, synthetic materials for neural regeneration can be improved chemically and biologically. Especially bioactivation of materials can be achieved by addition of small chemical moieties to the scaffold particularly found in specific tissues or addition of biologically active molecules derived from natural ECM. The ECM‐derived short peptides are promising candidates to be presented as functional domains on the scaffold surface for use in neural regeneration.