Self‐Assembled Proteins and Peptides as Scaffolds for Tissue Regeneration

Abstract

and their complex biological functions closely link to their high order organization; therefore such scaffolds need to mimic the hierarchical structure of natural tissues in order to provide the necessary structural and biomechanical framework. Furthermore, biomimetic scaffolds need to display the necessary biochemical and signaling cues for cellular function. The native ECM provides structural support and instructive cues to cells through the macromolecules found in its structure such as proteins, glycosaminoglycans and polysaccharides. ECM macromolecules contain bioactive signal sequences that are recognized by cells via cell transmembrane receptors called integrins. Interaction between integrins and bioactive epitopes of ECM activates signal transduction mechanisms, which can induce specifi c cellular functions including adhesion, migration, proliferation and differentiation. Such bioactive epitopes include: the RGD adhesive sequence found in the structure of ECM proteins such as fi bronectin and vitronectin, [ 1 ] the IKVAV peptide sequence from laminin known to induce neural attachment, migration and neurite outgrowth; [ 2 ] and the YIGSR peptide sequence derived from the laminin β-chain. [ 3 ] Moreover, the native ECM provides to cells a highly dynamic complex microenvironment that enables cell motility and time-varying display of bioactive cues via continuous matrix remodeling. In natural cellular microenvironment, ECM is constantly degraded by proteases and remodeled by proteins secreted from cells. Mimicking the ECM can therefore be the best strategy to develop advanced functional materials to control cellular behavior and Self-assembling proteins and peptides are increasingly gaining interest for potential use as scaffolds in tissue engineering applications. They selforganize from basic building blocks under mild conditions into supramolecular structures, mimicking the native extracellular matrix. Their properties can be easily tuned through changes at the sequence level. Moreover, they can be produced in suffi cient quantities with chemical synthesis or recombinant technologies to allow them to address homogeneity and standardization issues required for applications. Here. recent advances in self-assembling proteins, peptides, and peptide amphiphiles that form scaffolds suitable for tissue engineering are reviewed. The focus is on a variety of motifs, ranging from minimalistic dipeptides, simplistic ultrashort aliphatic peptides, and peptide amphiphiles to large "recombinamer" proteins. Special emphasis is placed on the rational design of self-assembling motifs and biofunctionalization strategies to infl uence cell behavior and modulate scaffold stability. Perspectives for combination of these "bottom-up" designer strategies with traditional "top-down" biofabrication techniques for new generations of tissue engineering scaffolds are highlighted.

Targeting Antitumoral Proteins to Breast Cancer by Local Administration of Functional Inclusion Bodies

“…[32] Some of them, such as the bovine α-lactalbumin [33] or the hen egg white lysozyme, [34] have already proved their utility as the basis of wide spectrum antitumoral drugs. [32] Some of them, such as the bovine α-lactalbumin [33] or the hen egg white lysozyme, [34] have already proved their utility as the basis of wide spectrum antitumoral drugs.…”

Bacterial Inclusion Bodies: Discovering Their Better Half

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Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles

“…The identification [2,3] and exploitation [4,5] of oligomerization domains, the tailored fibrillation of amyloidal protein forms [6] and the de novo design of protein-protein interacting patches [7,8] offer a wide spectrum of possibilities regarding the generation of supramolecular materials to be used in biological interfaces [9][10][11]. Being functional but also biocompatible and biodegradable, protein materials show a still unexplored biomedical potential in both regenerative medicine and conventional or cell-targeted drug delivery [12,13]. The natural tendency of GFP to oligomerize [14] and the more recent manipulation of GFP assembling [15,16] have attracted interest as this beta-sheet rich protein represents a compact, structurally stable building block for the assay of controlled oligomer formation and material characterization.…”