Using Mean Field Theory to Guide Biofunctional Materials Design

Abstract

research has revealed that, together with the provision of morphogens and the presentation of adhesion ligands, [ 2 ] the mechanical characteristics of extracellular matrices have a decisive infl uence on cell fate, provoking the development of materials with effective physical properties. [ 3 ] This interplay of biomolecular and biophysical signals thus defi nes an obvious, but until now unmet, need for a new generation of biomaterials that can be selectively and independently tuned for biomolecular properties and physical material parameters. A conceptual basis to address this need is currently missing. As such, we have developed a rational design approach relying on mean fi eld concepts to guide the design of biofunctional matrices. Considering the decisive role of electrostatic interactions in functional assemblies of living matter we selected a system that allows for a far-reaching modulation of structure-determining forces: crosslinking a hydrophilic and fl exible, multi-armed polymer (with four-armed, amino-terminated poly(ethylene glycol) (starPEG) as an example system known for its anti-adhesive characteristics towards proteins, [ 4 ] with a multifunctional, highly charged crosslinker (such as heparin (HEP) or a similarly charged glycosaminoglycan), which can function as a multivalent binding site capable of complexing a plethora of important bioactive molecules. [ 5 ] We explored whether and how the combination of the particular gel components permits varying the physical and biomolecular characteristics of the swollen materials independently.Based on the successful experimental verifi cation of the theoretical predictions and the functionalization of starPEG-heparin gels with adhesive ligand peptides (such as the integrinbinding arginine-glycine-aspartic acid sequence (RGD))) and morphogens (vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2)) through covalent and noncovalent conjugation schemes we were able to illustrate the resulting options for two selected example systems: studying the interplay of matrix elasticity and growth factor presentation in inducing the pro-angiogenic state of human endothelial cells and promoting osteogenic differentiation of human mesenchymal stem cells we identifi ed effective combinations of matrix parameters and demonstrated exciting options for the fully matrix controlled direction of the cells, i.e., removed the Using Mean Field Theory to Guide Biofunctional Materials DesignCell-instructive characteristics of extracellular matrices (ECM) resulting from a subtle balance of biomolecular and biophysical signals must be recapitulated in engineered biomaterials to facilitate regenerative therapies. However, no material explored so far allows the independent tuning of the involved molecular and physical cues due to the inherent correlation between biopolymer concentration and material properties. Addressing the resulting challenge, a rational design strategy for ECM-inspired biohybrid hydrogels based on multi-armed poly(ethylene glycol) and he...

Glycosaminoglycan‐Based Biohybrid Hydrogels: A Sweet and Smart Choice for Multifunctional Biomaterials

“…[4a] Based on this property, we developed a biohybrid hydrogel utilizing HEP as a major building block together with star-shaped PEG to form cell-instructive hydrogel matrices. [16] The high HEP concentration of the hydrogel allows the efficient administration of HEP-affine growth factors, such as FGF-2, [16] VEGF, [133] BMP-2, [134] SDF-1α, [135] GDNF, [136] NGF, [67] and TGF-β, [137] as well as the less-affine EGF. [138] Due to the high HEP concentration (i.e., the high number of protein-binding sites) in HEP-based hydrogels, multiple factors can be independently administered, as was shown for the parallel release of FGF-2 and VEGF [139] as well as FGF-2 and GDNF.…”

“…[134] A mean field approach was applied to identify conditions in which the balance of elastic, electrostatic/osmotic, and excluded volume forces resulted in a constant HEP volume density within starPEG-HEP hydrogels with gradually varied network properties (see Figure 18 A and B). Using this approach, the mechanical properties (storage moduli) of the biohybrid hydrogel could be varied over a broad range, from ~1 kPa to ~15 kPa, at an invariant HEP concentration (see Figure 18B).…”

Modular GAG-matrices to promote mammary epithelial morphogenesis in vitro

“…adhesion ligands, growth factors, etc.) [16, 17]. To assess the impact of biophysical properties of PEG-HEP matrices on MEC morphogenesis, the stiffness (storage modulus) of the hydrogels was increased to 1600 ± 350 Pa (Fig.…”

“…To this end, we developed a modular and multifunctional glycosaminoglycan- (GAG-) based matrix system wherein the mechanical and biochemical properties of the matrix are precisely and independently tuned to study their effects on mammary epithelial morphogenesis [16, 17]. GAGs are major components of ECMs and are involved in diverse biological processes, including growth factor presentation, ECM assembly, and cell adhesion [18, 19].…”

“…Incorporation of the GAG heparin into synthetic matrices allows precise control of biochemical properties, e.g. biomimetic application of growth factors and presentation of cell adhesion binding sites [17, 20-22]. The glycosaminoglycan building block is crosslinked by inert multi-arm starPEG or starPEG-peptide conjugates with a cell-degradable, matrix metalloproteinase-(MMP-) cleavable peptide sequence (GPQG↓IWGQ, the arrow indicating the cleavage site).…”