The extracellular matrix (ECM) is a complex, hierarchical material containing structural and bioactive components. This complexity makes decoupling the effects of biomechanical properties and cell-matrix interactions difficult, especially when studying cellular processes in a 3D environment. Matrix mechanics and cell adhesion are both known regulators of specific cellular processes such as stem cell proliferation and differentiation. However, more information is required about how such variables impact various neural lineages that could, upon transplantation, therapeutically improve neural function after a central nervous system injury or disease. Rapidly Assembling Pentapeptides for Injectable Delivery (RAPID) hydrogels are one biomaterial approach to meet these goals, consisting of a family of peptide sequences that assemble into physical hydrogels in physiological media. In this study, we studied our previously reported supramolecularly-assembling RAPID hydrogels functionalized with the ECM-derived cell-adhesive peptide ligands RGD, IKVAV, and YIGSR. Using molecular dynamics simulations and experimental rheology, we demonstrated that these integrin-binding ligands at physiological concentrations (3–12 m
The extracellular matrix (ECM) has force‐responsive (i.e., mechanochemical) properties that enable adaptation to mechanical loading through changes in fibrous network structure and interfiber bonding. Imparting such properties into synthetic fibrous materials will allow reinforcement under mechanical load, the potential for material self‐adhesion, and the general mimicking of ECM. Multifiber hydrogel networks are developed through the electrospinning of multiple fibrous hydrogel populations, where fibers contain complementary chemical moieties (e.g., aldehyde and hydrazide groups) that form covalent bonds within minutes when brought into contact under mechanical load. These fiber interactions lead to microscale anisotropy, as well as increased material stiffness and plastic deformation. Macroscale structures (e.g., tubes and layered scaffolds) are fabricated from these materials through interfiber bonding and adhesion when placed into contact while maintaining a microscale fibrous architecture. The design principles for engineering plasticity described can be applied to numerous material systems to introduce unique properties, from textiles to biomedical applications.
more » « less- NSF-PAR ID:
- 10458674
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 32
- Issue:
- 8
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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m ) did not impact the assembly of the KYFIL peptide system. In simulations, molecular measures of assembly such as hydrogen bonding and pi-pi interactions appeared unaffected by cell-adhesion sequence or concentration. Visualizations of clustering and analysis of solvent-accessible surface area indicated that the integrin-binding domains remained exposed. KYFIL or AYFIL hydrogels containing 3 mm of integrin-binding domains resulted in mechanical properties consistent with their non-functionalized equivalents. This strategy of doping RAPID gels with cell-adhesion sequences allows for the precise tuning of peptide ligand concentration, independent of the rheological properties. The controllability of the RAPID hydrogel system provides an opportunity to investigate the effect of integrin-binding interactions on encapsulated neural cells to discern how hydrogel microenvironment impacts growth, maturation, or differentiation. -
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