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Scientific Unit
Strategies for neural tissue repair heavily depend on our ability to temporally reconstruct the natural cellular microenvironment of neural cells. Biomaterials play a fundamental role in this context, as they provide the mechanical support for cells to attach and migrate to the injury site, as well as fundamental signals for differentiation. This review describes how different cellular processes (attachment, proliferation, and (directional) migration and differentiation) have been supported by different material parameters, in vitro and in vivo. Although incipient guidelines for biomaterial design become visible, literature in the field remains rather phenomenological. As in other fields of tissue regeneration, progress will depend on more systematic studies on cell-materials response, better understanding on how cells behave and understand signals in their natural milieu from neurobiology studies, and the translation of this knowledge into engineered microenvironments for clinical use.
Mechanically Reinforced Catechol-Containing Hydrogels with Improved Tissue Gluing Performance
(2017)
In situ forming hydrogels with catechol groups as tissue reactive functionalities are interesting bioinspired materials for tissue adhesion. Poly(ethylene glycol) (PEG)–catechol tissue glues have been intensively investigated for this purpose. Different cross-linking mechanisms (oxidative or metal complexation) and cross-linking conditions (pH, oxidant concentration, etc.) have been studied in order to optimize the curing kinetics and final cross-linking degree of the system. However, reported systems still show limited mechanical stability, as expected from a PEG network, and this fact limits their potential application to load bearing tissues. Here, we describe mechanically reinforced PEG–catechol adhesives showing excellent and tunable cohesive properties and adhesive performance to tissue in the presence of blood. We used collagen/PEG mixtures, eventually filled with hydroxyapatite nanoparticles. The composite hydrogels show far better mechanical performance than the individual components. It is noteworthy that the adhesion strength measured on skin covered with blood was >40 kPa, largely surpassing (>6 fold) the performance of cyanoacrylate, fibrin, and PEG–catechol systems. Moreover, the mechanical and interfacial properties could be easily tuned by slight changes in the composition of the glue to adapt them to the particular properties of the tissue. The reported adhesive compositions can tune and improve cohesive and adhesive properties of PEG–catechol-based tissue glues for load-bearing surgery applications
Abstract Living materials are an emergent material class, infused with the productive, adaptive, and regenerative properties of living organisms. Property regulation in living materials requires encoding responsive units in the living components to allow external manipulation of their function. Here, an optoregulated Escherichia coli (E. coli)-based living biomaterial that can be externally addressed using light to interact with mammalian cells is demonstrated. This is achieved by using a photoactivatable inducer of gene expression and bacterial surface display technology to present an integrin-specific miniprotein on the outer membrane of an endotoxin-free E. coli strain. Hydrogel surfaces functionalized with the bacteria can expose cell adhesive molecules upon in situ light-activation, and trigger cell adhesion. Surface immobilized bacteria are able to deliver a fluorescent protein to the mammalian cells with which they are interacting, indicating the potential of such a bacterial material to deliver molecules to cells in a targeted manner.
Strategies for regeneration after injury or during aging require the development of biomaterials able to reconstruct the essential components and properties of natural extracellular microenvironment. A particular feature in neural regeneration is the oriented disposition of neurons within nerves and cortex. In this thesis, through the spatiotemporal control of the availability of adhesive ligands at the surface of a biomaterial, these biomaterials allow directing the migration of neuron. This Thesis is structured in four parts. The first part presents microcontact printed patterns with adhesive compositions and geometries to allow directional migration and, uniquely, in vitro reconstruction of the somal translocation events occurring during cortical layering. In part 2 in situ directed neurites extension in defined directions is demonstrated using biomaterials functionalized with photo-activatable peptidomimetics of the laminin. In part 3 spatiotemporal and reversible regulations of actin dynamics in living cells is demonstrated using light-dosed delivery of Cytochalasin D. In the last part, the first demonstration of a light-regulated adhesive interaction between mammalian cells and a bacterial biointerface is provided.
The study of the actin cytoskeleton and related cellular processes requires tools to specifically interfere withactin dynamics in living cell cultures, ideally with spatiotemporal control and compatible with real time imaging.A phototriggerable derivative of the actin disruptor Cytochalasin D (CytoD) is described and tested here. Itincludes a nitroveratryloxycarbonyl (Nvoc) photoremovable protecting group (PPG) at the hydroxyl group atC7 of CytoD. The attachment of the PPG renders Nvoc-CytoD temporarily inactive, and enables light-doseddelivery of the active drug CytoD to living cells. This article presents the full structural and physicochemicalcharacterization, the toxicity analysis. It is complemented with biological tests to show the time scales(seconds) and spatial resolution (cellular level) achievable with a UV source in a regular microscopy setup.
