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The development of brain in vitro models requires the application of novel biocompatible materials and biopolymers as scaffolds for controllable and effective cell growth and functioning. The “ideal” brain in vitro model should demonstrate the principal features of brain plasticity like synaptic transmission and remodeling, neurogenesis and angiogenesis, and changes in the metabolism associated with the establishment of new intercellular connections. Therefore, the extracellular scaffolds that are helpful in the establishment and maintenance of local microenvironments supporting brain plasticity mechanisms are of critical importance. In this review, we will focus on some carbohydrate metabolites—lactate, pyruvate, oxaloacetate, malate—that greatly contribute to the regulation of cell-to-cell communications and metabolic plasticity of brain cells and on some resorbable biopolymers that may reproduce the local microenvironment enriched in particular cell metabolites.