Nanoscale engineering of biomimetic surfaces: cues from the extracellular matrix

Abstract

The ultimate goal in the design of biomimetic materials for use in tissue engineering as permanent or resorbable tissue implants is to generate biocompatible scaffolds with appropriate biomechanical and chemical properties to allow the adhesion, ingrowth, and survival of cells. Recent efforts have therefore focused on the construction and modification of biomimetic surfaces targeted to support tissue-specific cell functions including adhesion, growth, differentiation, motility, and the expression of tissue-specific genes. Four decades of extensive research on the structure and biological influence of the extracellular matrix (ECM) on cell behavior and cell fate have shown that three types of information from the ECM are relevant for the design of biomimetic surfaces: (1) physical properties (elasticity, stiffness, resilience of the cellular environment), (2) specific chemical signals from peptide epitopes contained in a wide variety of extracellular matrix molecules, and (3) the nanoscale topography of microenvironmental adhesive sites. Initial physical and chemical approaches aimed at improving the adhesiveness of biomaterial surfaces by sandblasting, particle coating, or etching have been supplemented by attempts to increase the bioactivity of biomaterials by coating them with ECM macromolecules, such as fibronectin, elastin, laminin, and collagens, or their integrin-binding epitopes including RGD, YIGSR, and GFOGER. Recently, the development of new nanotechnologies such as photo- or electron-beam nanolithography, polymer demixing, nano-imprinting, compression molding, or the generation of TiO(2) nanotubes of defined diameters (15-200 nm), has opened up the possibility of constructing biomimetic surfaces with a defined nanopattern, eliciting tissue-specific cellular responses by stimulating integrin clustering. This development has provided new input into the design of novel biomaterials. The new technologies allowing the construction of a geometrically defined microenvironment for cells at the nanoscale should facilitate the investigation of nanotopography-dependent mechanisms of integrin-mediated cell signaling.

Basement Membranes: Cell Scaffoldings and Signaling Platforms

“…It has recently been discovered, for example, that recombinant laminin-511 is an outstanding substrate to maintain mouse and human stem cells in a pluripotent state, whereas the laminin in a more complex environment has been reported to drive pancreatic differentiation (Domogatskaya et al 2008;Higuchi et al 2010;Rodin et al 2010). Basement membrane components are also being used to modify the surface properties of biomimetic materials for use in tissue engineering, e.g., nerve conduits (reviewed in von der Mark et al 2010). …”

Pancreas organogenesis: From bud to plexus to gland

“…This latter point may be critical given the tissue complexities and multiple interactions that we have reviewed, and optimizing the 3-D culture system to include ECM components reminiscent of the developing pancreas should be considered. One could also find ways of tricking hESC grown in vitro into responding as if they were in the normal 3-D environment, and approaching novel biopolymers for support and differentiation (Kreger et al, 2010), even in combination with nanoscale bioengineering (von der Mark et al, 2010), could be excellent supplemental directions.…”

Cell-material interaction

“…The presence and organisation of individual proteins depend on the type of tissue. Coating of implant materials with full-length extracellular matrix proteins has shown to stimulate cell adhesion, proliferation, or differentiation [1,70]. Matrix proteins can be adsorbed to nearly all biomaterial surfaces, including metals, ceramics, and organic polymers.…”

“…The adsorption process can cause protein to undergo conformational changes and denaturation, which can lead to a foreign body response when implanted into the body. In addition, isolation and purification of native proteins at larger scale for tissue engineering approaches is expensive [70]. Therefore, the generation of integrin receptor ligands on material surfaces is focused on peptide domains of the matrix proteins.…”