Supramolecular hydrogels for regenerative medicine

\u3cp\u3eRegenerative medicine is the science of re-creating or repairing living functional tissue, often inside the body. Biomaterials for regenerative medicine are inspired by the extracellular matrix (ECM), which provides the natural scaffold for cells inside the body. The use of supramolecular hydrogels as man-made tunable replacements for the ECM is being investigated because hydrogels offer an aqueous environment. In addition, supramolecular systems offer modularity and dynamics, also found in the ECM. This chapter gives an overview of translational research on different supramolecular hydrogels, showing systems that have been used in vivo in the field of regenerative medicine. We discuss the chemical structures and biomedical applications of various natural compounds, biosynthetic compounds, biohybrid systems, and fully synthetic materials. Furthermore, we discuss tuning of the mechanical properties and functionalization of these hydrogels with bioactive compounds. Both characteristics are essential for their function in contact with cells and for the creation of a regenerative niche, thereby controlling cellular adherence, proliferation, homing, and differentiation.\u3c/p\u3

Cell and protein fouling properties of polymeric mixtures containing supramolecular poly(ethylene glycol) additives

\u3cp\u3eFouling properties of new biomaterials are important for the performance of a material in a biological environment. Here, a set of three supramolecular polymeric additives consisting of ureidopyrimidinone (UPy)-functionalized poly(ethylene glycol) (UPyPEG) were formulated with UPy-modified polycaprolactone into thin supramolecular material films. The antifouling properties of these material films were determined by investigation of the relation of cell adhesion and protein adsorption on these materials films. The presence of the UPyPEG additives at the surface of the films was evident by an increased hydrophilicity. Adhesion of human epithelial and endothelial cells was strongly reduced for two of the UPyPEG-containing films. Analysis of adsorption of the first three proteins from the Vroman series, albumin, γ-globulin, and fibrinogen, using quartz crystal microbalance with dissipation in combination with viscoelastic modeling, revealed that the surfaces containing the UPyPEG additives had a limited effect on adsorption of these proteins. Despite a limited reduction of protein adsorption, UPyPEG-containing mixtures were non-cell-adhesive, which shows that non-cell-adhesive properties of supramolecular polymer surfaces are not always directly correlated to protein adsorption.\u3c/p\u3

Materiomics using synthetic materials:Metals, cements, covalent polymers and supramolecular systems

\u3cp\u3eTo screen biomaterials in a materiomics approach, libraries of materials are produced. Different materials are used, varying from metals and cements, to covalent polymers that can be either premixed or polymerized in situ, to supramolecular systems that can be applied in a modular approach. This chapter describes the generation of such libraries using different kinds of materials and chemistries. Additionally, the advantages and limitations of the application of these different systems/biomaterials in a materiomics approach are discussed. Different synthetic biomaterials are used for many biomedical applications, varying from metals and ceramic cements, to polymers and supramolecular systems. To screen these biomaterials in a materiomics approach, as said above, libraries of materials are produced. Variations in biomaterials are screened as continuous gradients or in a discrete fashion. The properties that are varied and methods used to create variation within these libraries depend on the type of biomaterial. For the hard metal and ceramic-based biomaterials, the surface interaction with tissue is the property of most interest, and therefore properties such as surface roughness and topography are varied. Covalent polymers are diversified using combinatorial chemistry. The dynamic and self-assembling nature of supramolecular systems allows for the development of material libraries using a modular approach by mixing and matching of different compounds modified with supramolecular moieties.\u3c/p\u3

An injectable and drug-loaded supramolecular hydrogel for local catheter injection into the pig heart

Supramolecular hydrogelators based on ureido-pyrimidinones allow full control over the macroscopic gel properties and the sol–gel switching behavior using pH. Here, we present a protocol for formulating and injecting such a supramolecular hydrogelator via a catheter delivery system for local delivery directly in relevant areas in the pig heart

A fast pH-switchable and self-healing supramolecular hydrogel carrier for guided, local catheter-injection in the infarcted myocardium

Minimally invasive intervention strategies after myocardial infarction use state-of-the-art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH-switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1-m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self-healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model