Extracellular macrostructure anisotropy improves cardiac tissue-like construct function and phenotypic cellular maturation.

Regenerative cardiac tissue is a promising field of study with translational potential as a therapeutic option for myocardial repair after injury, however, poor electrical and contractile function has limited translational utility. Emerging research suggests scaffolds that recapitulate the structure of the native myocardium improve physiological function. Engineered cardiac constructs with anisotropic extracellular architecture demonstrate improved tissue contractility, signaling synchronicity, and cellular organization when compared to constructs with reduced architectural order.

Adjusting the physico-chemical properties of collagen scaffolds to accommodate primary osteoblasts and endothelial cells.

Collagen-based biomaterials are used widely as tissue engineering scaffolds because of their excellent bioactivity and their similarity to the natural ECM. The regeneration of healthy bone tissue requires simultaneous support for both osteoblasts and, where angiogenesis is intended, endothelial cells. Hence it is important to tailor carefully the biochemical and structural characteristics of the scaffold to suit the needs of each cell type.

Avoiding artefacts in MicroCT imaging of collagen scaffolds: Effect of phosphotungstic acid (PTA)-staining and crosslink density.

X-ray micro-computed tomography (μ-CT) can be used to provide both qualitative and quantitative information on the structure of three-dimensional (3D) bioactive scaffolds. When performed in a dry state, μ-CT accurately reflects the structure of collagen-based scaffolds, but imaging in a wet state offers challenges with radiolucency. Here we have used phosphotungstic acid (PTA) as a contrast agent to visualise fully hydrated collagen scaffolds in a physiologically relevant environment.

Tailoring the biofunctionality of collagen biomaterials via tropoelastin incorporation and EDC-crosslinking.

Recreating the cell niche of virtually all tissues requires composite materials fabricated from multiple extracellular matrix (ECM) macromolecules. Due to their wide tissue distribution, physical attributes and purity, collagen, and more recently, tropoelastin, represent two appealing ECM components for biomaterials development. Here we blend tropoelastin and collagen, harnessing the cell-modulatory properties of each biomolecule.

Collagen Film Activation with Nanoscale IKVAV-Capped Dendrimers for Selective Neural Cell Response.

Biocompatible neural guidance conduits are alternatives to less abundant autologous tissue grafts for small nerve gap injuries. To address larger peripheral nerve injuries, it is necessary to design cell selective biomaterials that attract neuronal and/or glial cells to an injury site while preventing the intrusion of fibroblasts that cause inhibitory scarring. Here, we investigate a potential method for obtaining this selective cellular response by analysing the responses of rat Schwann cells and human dermal fibroblasts to isoleucine-lysine-valine-alanine-valine (IKVAV)-capped dendrimer-activated collagen films.

Collagen scaffolds functionalized with triple-helical peptides support 3D HUVEC culture.

Porous biomaterials which provide a structural and biological support for cells have immense potential in tissue engineering and cell-based therapies for tissue repair. Collagen biomaterials that can host endothelial cells represent promising tools for the vascularization of engineered tissues. Three-dimensional collagen scaffolds possessing controlled architecture and mechanical stiffness are obtained through freeze-drying of collagen suspensions, followed by chemical cross-linking which maintains their stability.

Poly-l-Lactic Acid Nanotubes as Soft Piezoelectric Interfaces for Biology: Controlling Cell Attachment Polymer Crystallinity.

It has become increasingly evident that the mechanical and electrical environment of a cell is crucial in determining its function and the subsequent behavior of multicellular systems. Platforms through which cells can directly interface with mechanical and electrical stimuli are therefore of great interest. Piezoelectric materials are attractive in this context because of their ability to interconvert mechanical and electrical energy, and piezoelectric , in particular, are ideal candidates for tools within mechanobiology, given their ability to both detect and apply small forces on a length scale that is compatible with cellular dimensions.

Impact of UV- and carbodiimide-based crosslinking on the integrin-binding properties of collagen-based materials.

Collagen constructs are widely used for tissue engineering. These are frequently chemically crosslinked, using EDC, to improve their stability and tailor their physical properties. Although generally biocompatible, chemical crosslinking can modify crucial amino acid side chains, such as glutamic acid, that are involved in integrin-mediated cell adhesion.

Cellular response to collagen-elastin composite materials.

Collagen is used extensively in tissue engineering due to its biocompatibility, near-universal tissue distribution, low cost and purity. However, native tissues are composites that include diverse extracellular matrix components, which influence strongly their mechanical and biological properties. Here, we provide important new findings on the differential regulation, by collagen and elastin, of the bio-response to the composite material.

Plasma processing of PDMS based spinal implants for covalent protein immobilization, cell attachment and spreading.

PDMS is widely used for prosthetic device manufacture. Conventional ion implantation is not a suitable treatment to enhance the biocompatibility of poly dimethyl siloxane (PDMS) due to its propensity to generate a brittle silicon oxide surface layer which cracks and delaminates. To overcome this limitation, we have developed new plasma based processes to balance the etching of carbon with implantation of carbon from the plasma source.

Correction to: Evaluation of cell binding to collagen and gelatin: a study of the effect of 2D and 3D architecture and surface chemistry.

The article "Evaluation of cell binding to collagen and gelatin: a study of the effect of 2D and 3D architecture and surface chemistry", written by Natalia Davidenko, Carlos F. Schuster, Daniel V. Bax, Richard W.

Selecting the correct cellular model for assessing of the biological response of collagen-based biomaterials.

Unlabelled: Accurate evaluation of the biological performance of biomaterials requires the correct assessment of their native-like cell ligation properties. However, cell attachment studies often overlook the details of the substrate-cell binding mechanisms, be they integrin-mediated or non-specific, and ignore the class- and species-specificities of the cell adhesion receptor involved. In this work we have used different collagen (Col) substrates (fibrillar collagens I, II and III and network-forming Col IV), containing different affinity cell-recognition motifs, to establish the influence of the receptor identity and species-specificity on collagen-cell interactive properties.

Fundamental insight into the effect of carbodiimide crosslinking on cellular recognition of collagen-based scaffolds.

Unlabelled: Research on the development of collagen constructs is extremely important in the field of tissue engineering. Collagen scaffolds for numerous tissue engineering applications are frequently crosslinked with 1-ethyl-3-(3-dimethylaminopropyl-carbodiimide hydrochloride (EDC) in the presence of N-hydroxy-succinimide (NHS). Despite producing scaffolds with good biocompatibility and low cellular toxicity the influence of EDC/NHS crosslinking on the cell interactive properties of collagen has been overlooked.

Evaluation of cell binding to collagen and gelatin: a study of the effect of 2D and 3D architecture and surface chemistry.

Studies of cell attachment to collagen-based materials often ignore details of the binding mechanisms-be they integrin-mediated or non-specific. In this work, we have used collagen and gelatin-based substrates with different dimensional characteristics (monolayers, thin films and porous scaffolds) in order to establish the influence of composition, crosslinking (using carbodiimide) treatment and 2D or 3D architecture on integrin-mediated cell adhesion. By varying receptor expression, using cells with collagen-binding integrins (HT1080 and C2C12 L3 cell lines, expressing α2β1, and Rugli expressing α1β1) and a parent cell line C2C12 with gelatin-binding receptors (αvβ3 and α5β1), the nature of integrin binding sites was studied in order to explain the bioactivity of different protein formulations.

Optimisation of UV irradiation as a binding site conserving method for crosslinking collagen-based scaffolds.

Short wavelength (λ = 254 nm) UV irradiation was evaluated over a range of intensities (0.06 to 0.96 J/cm(2)) as a means of cross-linking collagen- and gelatin-based scaffolds, to tailor their material characteristics whilst retaining biological functionality.

Characterization of Endothelial Progenitor Cell Interactions with Human Tropoelastin.

The deployment of endovascular implants such as stents in the treatment of cardiovascular disease damages the vascular endothelium, increasing the risk of thrombosis and promoting neointimal hyperplasia. The rapid restoration of a functional endothelium is known to reduce these complications. Circulating endothelial progenitor cells (EPCs) are increasingly recognized as important contributors to device re-endothelialization.

Surface plasma modification and tropoelastin coating of a polyurethane co-polymer for enhanced cell attachment and reduced thrombogenicity.

Polymers currently utilized for dermal and vascular applications possess sub-optimal biocompatibility which reduces their efficacy. Improving the cell-binding and blood-contacting properties of these polymers would substantially improve their clinical utility. Tropoelastin is a highly extensible extracellular matrix protein with beneficial cell interactive and low thrombogenic properties.

Immobilisation of a fibrillin-1 fragment enhances the biocompatibility of PTFE.

Current vascular biomaterials exhibit poor biocompatibility characterised by failure to promote endothelialisation, predisposition to neoinitmal hyperplasia and excessive thrombogenicity. Fibrillin-1, a major constituent of microfibrils is associated with elastic fibres in the arterial wall. Fibrillin-1 binds to endothelial cells through an RGD cell adhesion motif in the fourth TB module.

A novel cell adhesion region in tropoelastin mediates attachment to integrin αVβ5.

Tropoelastin protein monomers assemble to form elastin. Cellular integrin αVβ3 binds RKRK at the C-terminal tail of tropoelastin. We probed cell interactions with tropoelastin by deleting the RKRK sequence to identify other cell-binding interactions within tropoelastin.

Cell patterning via linker-free protein functionalization of an organic conducting polymer (polypyrrole) electrode.

The interaction of proteins and cells with polymers is critical to their use in scientific and medical applications. In this study, plasma immersion ion implantation (PIII) was used to modify the surface of the conducting polymer, polypyrrole, which possesses electrical properties. PIII treatment enabled persistent, covalent binding of the cell adhesive protein, tropoelastin, without employing chemical linking molecules.

Molecular orientation of tropoelastin is determined by surface hydrophobicity.

Tropoelastin is the precursor of the extracellular protein elastin and is utilized in tissue engineering and implant technology by adapting the interface presented by surface-bound tropoelastin. The preferred orientation of the surface bound protein is relevant to biointerface interactions, as the C-terminus of tropoelastin is known to be a binding target for cells. Using recombinant human tropoelastin we monitored the binding of tropoelastin on hydrophilic silica and on silica made hydrophobic by depositing a self-assembled monolayer of octadecyl trichlorosilane.

Free radical functionalization of surfaces to prevent adverse responses to biomedical devices.

Immobilizing a protein, that is fully compatible with the patient, on the surface of a biomedical device should make it possible to avoid adverse responses such as inflammation, rejection, or excessive fibrosis. A surface that strongly binds and does not denature the compatible protein is required. Hydrophilic surfaces do not induce denaturation of immobilized protein but exhibit a low binding affinity for protein.

Directed cell attachment by tropoelastin on masked plasma immersion ion implantation treated PTFE.

The ability to generate cell patterns on polymer surfaces is critical for the detailed study of cellular biology, the fabrication of cell-based biosensors, cell separation techniques and for tissue engineering. In this study contact tape masking and steel shadow masks were used to exclude plasma immersion ion implantation (PIII) treatment from defined areas of polytetrafluoroethylene (PTFE) surfaces. This process enabled patterned covalent binding of the cell adhesive protein, tropoelastin, without employing chemical linking molecules.

Binding of the cell adhesive protein tropoelastin to PTFE through plasma immersion ion implantation treatment.

The interaction of proteins and cells with polymers is critical to their use in scientific and medical applications. In this study, plasma immersion ion implantation (PIII) was used to modify the surface of polytetrafluorethylene (PTFE), enabling the covalent binding of a cell adhesive protein, tropoelastin, without employing chemical linking molecules. Tropoelastin coating of untreated or PIII treated PFTE simultaneously promoted and blocked cell interactions respectively, i.

Stability of a therapeutic layer of immobilized recombinant human tropoelastin on a plasma-activated coated surface.

Purpose: To modify blood-contacting stainless surfaces by covalently coating them with a serum-protease resistant form of tropoelastin (TE). To demonstrate that the modified TE retains an exposed, cell-adhesive C-terminus that persists in the presence of blood plasma proteases.

Methods: Recombinant human TE and a point mutant variant (R515A) of TE were labeled with (125)Iodine and immobilized on plasma-activated stainless steel (PAC) surfaces.