ABSTRACT
Optimization of cell-material interactions is crucial for the success of synthetic biomaterials in guiding tissue regeneration. To do so, catechol chemistry is often used to introduce adhesiveness into biomaterials. Here, a supramolecular approach based on ureido-pyrimidinone (UPy) modified polymers is combined with catechol chemistry in order to achieve improved cellular adhesion onto supramolecular biomaterials. UPy-modified hydrophobic polymers with non-cell adhesive properties are developed that can be bioactivated via a modular approach using UPy-modified catechols. It is shown that successful formulation of the UPy-catechol additive with the UPy-polymer results in surfaces that induce cardiomyocyte progenitor cell adhesion, cell spreading, and preservation of cardiac specific extracellular matrix production. Hence, by functionalizing supramolecular surfaces with catechol functionalities, an adhesive supramolecular biomaterial is developed that allows for the possibility to contribute to biomaterial-based regeneration.
Subject(s)
Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Catechols/chemistry , Catechols/pharmacology , Cell Adhesion/drug effects , Cell Line , Cell Survival/drug effects , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Gene Expression Regulation/drug effects , Polymers/chemistry , Pyrimidinones/chemistry , Surface PropertiesABSTRACT
In the cardiac microenvironment, cardiomyocytes (CMs) are embedded in an aligned and structured extracellular matrix (ECM) to maintain the coordinated contractile function of the heart. The cardiac fibroblast (cFB) is the main cell type responsible for producing and remodeling this matrix. In cardiac diseases, however, adverse remodeling and CM death may lead to deterioration of the aligned myocardial structure. Here, we present an in vitro cardiac model system with uniaxial and biaxial constraints to induce (an)isotropy in 3D microtissues, thereby mimicking 'healthy' aligned and 'diseased' disorganized cardiac matrices. A mixture of neonatal mouse CMs and cFBs was resuspended in a collagen-matrigel hydrogel and seeded to form microtissues to recapitulate the in vivo cellular composition. Matrix disarray led to a stellate cell shape and a disorganized sarcomere organization, while CMs in aligned matrices were more elongated and had aligned sarcomeres. Although matrix disarray has no detrimental effect on the force generated by the CMs, it did have a negative effect on the homogeneity of contraction force distribution. Furthermore, proliferation of the cFBs affected microtissue contraction as indicated by the negative correlation between the percentage of cFBs in the microtissues and their beating frequency. These results suggest that in regeneration of the diseased heart, reorganization of the disorganized matrix will contribute to recover the coordinated contraction but restoring the ratio in cellular composition (CMs and cFBs) is also a prerequisite to completely regain tissue function.
