An In Vitro Model of the Blood-Brain Barrier for the Investigation and Isolation of the Key Drivers of Barriergenesis.

The blood-brain barrier (BBB) tightly regulates substance transport between the bloodstream and the brain. Models for the study of the physiological processes affecting the BBB, as well as predicting the permeability of therapeutic substances for neurological and neurovascular pathologies, are highly desirable. Existing models, such as Transwell utilizing-models, do not mimic the extracellular environment of the BBB with their stiff, semipermeable, non-biodegradable membranes.

Bioinspired mineralization of engineered living materials to promote osteogenic differentiation.

In this work, Engineered Living Materials (ELMs), based on the combination of genetically-modified bacteria and mineral-reinforced organic matrices, and endowed with self-healing or regenerative properties and adaptation to specific biological environments were developed. Concretely, we produced ELMs combining human mesenchymal stem cells (hMSCs) and Lactococcus lactis (L. lactis), which was specifically programmed to deliver bone morphogenetic protein (BMP-2) upon external stimulation using nisin, into mineralized alginate matrices.

Living Biomaterials to Engineer Hematopoietic Stem Cell Niches.

Living biointerfaces are a new class of biomaterials combining living cells and polymeric matrices that can act as biologically active and instructive materials that host and provide signals to surrounding cells. Here, living biomaterials based on Lactococcus lactis to control hematopoietic stem cells in 2D surfaces and 3D hydrogels are introduced. L.

Borax induces osteogenesis by stimulating NaBC1 transporter via activation of BMP pathway.

The intrinsic properties of mesenchymal stem cells (MSCs) make them ideal candidates for tissue engineering applications. Efforts have been made to control MSC behavior by using material systems to engineer synthetic extracellular matrices and/or include soluble factors in the media. This work proposes a simple approach based on ion transporter stimulation to determine stem cell fate that avoids the use of growth factors.

Simultaneous Boron Ion-Channel/Growth Factor Receptor Activation for Enhanced Vascularization.

Boron ion is essential in metabolism and its concentration is regulated by ion-channel NaBC1. NaBC1 mutations cause corneal dystrophies such as Harboyan syndrome. Here a 3D molecular model for NaBC1 is proposed and it is shown that simultaneous stimulation of NaBC1 and vascular endothelial growth factor receptors (VEGFR) promotes angiogenesis in vitro and in vivo with ultralow concentrations of VEGF.

Bacteria-Based Materials for Stem Cell Engineering.

Materials can be engineered to deliver specific biological cues that control stem cell growth and differentiation. However, current materials are still limited for stem cell engineering as stem cells are regulated by a complex biological milieu that requires spatiotemporal control. Here a new approach of using materials that incorporate designed bacteria as units that can be engineered to control human mesenchymal stem cells (hMSCs), in a highly dynamic-temporal manner, is presented.

Engineered microenvironments for synergistic VEGF - Integrin signalling during vascularization.

We have engineered polymer-based microenvironments that promote vasculogenesis both in vitro and in vivo through synergistic integrin-growth factor receptor signalling. Poly(ethyl acrylate) (PEA) triggers spontaneous organization of fibronectin (FN) into nanonetworks which provide availability of critical binding domains. Importantly, the growth factor binding (FNIII) and integrin binding (FNIII) regions are simultaneously available on FN fibrils assembled on PEA.

Living biointerfaces based on non-pathogenic bacteria support stem cell differentiation.

Lactococcus lactis, a non-pathogenic bacteria, has been genetically engineered to express the III7-10 fragment of human fibronectin as a membrane protein. The engineered L. lactis is able to develop biofilms on different surfaces (such as glass and synthetic polymers) and serves as a long-term substrate for mammalian cell culture, specifically human mesenchymal stem cells (hMSC).

Borax-Loaded PLLA for Promotion of Myogenic Differentiation.

Boron is an essential metalloid, which plays a key role in plant and animal metabolisms. It has been reported that boron is involved in bone mineralization, has some uses in synthetic chemistry, and its potential has been only recently exploited in medicinal chemistry. However, in the area of tissue engineering, the use of boron is limited to works involving certain bioactive glasses.

Controlled Assembly of Fibronectin Nanofibrils Triggered by Random Copolymer Chemistry.

Fibronectin fibrillogenesis is the physiological process by which cells elaborate a fibrous FN matrix. Poly(ethyl acrylate), PEA, has been described to induce a similar process upon simple adsorption of fibronectin (FN) from a protein solution-in the absence of cells-leading to the so-called material-driven fibronectin fibrillogenesis. Poly(methyl acrylate), PMA, is a polymer with very similar chemistry to PEA, on which FN is adsorbed, keeping the globular conformation of the protein in solution.

Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation.

Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII(7-10) fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII(7-10) fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L.

Functional living biointerphases.

Lactococcus lactis is modified to express a fibronectin fragment (FNIII₇₋₁₀) as a membrane protein. This interphase, based on a living system, can be further exploited to provide spatio-temporal factors to direct cell function at the material interface. This approach establishes a new paradigm in biomaterial surface functionalization for biomedical applications.