Professor of Orthopaedic Surgery and Biomedical Engineering Department of Orthopedic Surgery, University of California, Davis, United States
Introduction: The extracellular matrix (ECM) is the fabric that supports tissue-specific functions of associated cells by presenting a complex milieu of soluble and insoluble signals. Biomaterial design provides an exciting opportunity to mimic the endogenous ECM in order to regulate the survival and function of relevant cell populations. Furthermore, biomaterials can be engineered to model both healthy and diseased ECMs to understand the physiological development or reveal new targets in the pathophysiology of cells in disease. Key biophysical characteristics of natural and synthetic biomaterials can be manipulated to interrogate cell behavior. For example, macroporous composite scaffolds made from synthetic aliphatic polyesters such as poly(lactide-co-glycolide) and synthetic bone-like minerals are used to model the mineralized characteristics of bone tissue as models for bone development or metastasis of primary cancers to bone tissue. Hydrogels derived from natural and/or synthetic polymers can be readily engineered to explore the influence of stiffness, viscoelasticity, matrix composition, and even porosity on a range of cell response including angiogenesis, tumorigenesis, macrophage polarization, and migration of cell aggregates or organoids. These biomaterials induce dramatic effects on associated cells, and cell response can provide clues for how to regulate the behavior of cells for therapeutic purposes. Essential ECM components have been identified that promote cell adhesion, migration, self-assembly into larger structures, and differentiation. However, this bottom-up approach to biomaterials design, commonly employing individual proteins or functional peptide sequences of proteins, fails to capture beneficial interactions with other ligands and restricts the potential benefit of ECMs to guide cell fate. Cell-secreted ECMs preserve the complex nature of ECMs and have utility as bioactive platforms to instruct stem and progenitor cells. Following decellularization, acellular ECMs can be used as coatings on various substrates to recapitulate physical and chemical cues that guide cell function. Furthermore, the composition and function of these engineered ECMs can be designed by manipulating the cell culture conditions during deposition. Our laboratory has used these cell secreted ECMs as drug delivery vehicles, coatings on macroporous scaffolds, and substrates to modulate survival and differentiation. Moreover, these constituents can be combined with substrates containing novel morphology to guide progenitor cell differentiation toward bone, cartilage, and other lineages.
