The Use of Small-Molecule Compounds for Cell Adhesion and Migration in Regenerative Medicine

Cell adhesion is essential for cell survival, communication, and regulation, and it is of fundamental importance in the development and maintenance of tissues. Cell adhesion has been widely explored due to its many important roles in the fields of tissue regenerative engineering and cell biology. This is because the mechanical interactions between a cell and its extracellular matrix (ECM) can influence and control cell behavior and function. Currently, biomaterials for regenerative medicine have been heavily investigated as substrates for promoting a cells' adhesive properties and subsequent proliferation, tissue differentiation, and maturation. Specifically, the manipulation of biomaterial surfaces using ECM coatings such as fibronectin extracted from animal-derived ECM have contributed significantly to tissue regenerative engineering as well as basic cell biology research. Additionally, synthetic and natural bioadhesive agents with pronounced abilities to enhance adhesion in numerous biological components and molecules have also been assessed in the field of tissue regeneration. Research into the use of facilitative bioadhesives has aimed to further optimize the biocompatibility, biodegradability, toxicity levels, and crosslinking duration of bioadhesive materials for improved targeted delivery and tissue repair. However, the restrictive drawbacks of some of these bioadhesive and animal-derived materials include the potential risk of disease transmission, immunogenicity, poor reproducibility, impurities, and instability. Therefore, it is necessary for alternative strategies to be sought out to improve the quality of cell adhesion to biomaterials. One promising strategy involves the use of cell-adhesive small molecules. Small molecules are relatively inexpensive, stable, and low-molecular-weight (<1000 Da) compounds with great potential to serve as efficient alternatives to conventional bioadhesives, ECM proteins, and other derived peptides. Over the past few years, a number of cell adhesive small molecules with the potential for tissue regeneration have been reported. In this review, we discuss the current progress using cell adhesive small molecules to regulate tissue regeneration.