We are grateful to M. instruct cell responses through a control of the cell adhesion pathway activation play a crucial role in tissue engineering and have been thoroughly investigated in several studies.1 Unlike natural polymers, synthetic polymeric biomaterials used in tissue engineering applications lack biological activity and typically do not promote excellent cell adhesion and growth. Therefore, scaffold functionalization with growth factors, adhesion peptides, and cytokines BQ-788 has been receiving considerable attention since it plays an important role in the communication and information transfer between the cells and their microenvironment.2 The control of cell adhesion, so that particular signaling pathways would be enhanced or suppressed, can be achieved through bioactive scaffolds that are able to engage cells through specific integrins.3 Integrins are a family of cell adhesion receptors4 constituted of two independent subunits, alpha () and beta (), which in mammals assemble into 24 heterodimeric pairs each with peculiar functions and tissue specificity. Integrins are not just adhesion receptors that mediate dynamic adhesive cellCcell and cellCmatrix interactions, but they can transmit information into cells to regulate migration, survival, and growth. The activation of intracellular signaling pathways, called outside-in signaling, occurs upon the binding of specific ligands in the extracellular domain of the integrins.5a The outside-in signaling, in turn, triggers a vast array of intracellular signaling events that control cell shape, motility, proliferation, and cell-type-specific gene expression.5b Several studies were devoted to finding non-natural ligands which inhibit integrin function (antagonists), and some preclinical studies suggested that integrin antagonists might be useful to suppress tumor angiogenesis and growth.6 Less attention was addressed to those ligands that promote integrin activation, but it was recently found that integrin agonists could open novel opportunities for therapeutics, which gain benefits in increasing rather than reducing integrin-dependent adhesion.7 Recently, a novel series of monocyclic -lactam derivatives was designed and synthesized by a structure-based strategy to target RGD-binding and leukocyte integrins.8 From a biological standpoint, the -lactam ring is considered to be a privileged structure because of its peculiar heterocyclic platform able to provide ligands BQ-788 with different pharmacological profiles.9 The chemical structure of the new integrin ligands was designed with an amine, a carboxylate side chain, and the -lactam ring as a site of conformational restriction to provide a favorable alignment within the receptor to satisfy the crucial requirements for integrin affinity and selectivity. The library of -lactam derivatives was evaluated by investigating the effects on integrin-mediated cell adhesion and signaling BQ-788 in cell lines overexpressing integrins v3, v5, v6, 51, IIb3, 41, and L2.8a Among the new compounds, potent agonists that could induce cell adhesion and promote cell signaling mediated by integrins v3, v5, 51, or 41 were successfully obtained.8 To stimulate cell adhesion on biomaterials, some adhesive peptides that contain the RGD tripeptide were used.10 However, it would be important to consider the RGD sequence is identified by different integrin classes, so the specificity of cell activation BQ-788 could be highly limited.11 On the contrary, the use of the new -lactam integrin agonists could provide the possibility to generate new functional biomaterials with targeted cell specificity because of the integrin selectivity exerted by the new ligands. Electrospinning is definitely a powerful technology to fabricate nanofibrous scaffolds.12 The great potential of electrospun systems is mainly indicated in the biomedical field where they are employed for cells engineering applications, drug delivery Itgb1 systems, diagnostics, and as biosensors.13 Most of the functionalization approaches of electrospun scaffolds with biomoleculessuch as growth factor, nucleic acids, cell adhesive peptides, therapeutic molecules, bioprobes, and integrin-binding ligandsare related.