The complexity and dynamism of biological tissues present a myriad of challenges for understanding these living composites, and for rebuilding them to benefit human health. Fortunately, this biological complexity can also serve as a boon to biomedical engineers by offering multifunctional cellular workhorses that are already predisposed to perform unique tasks. Arguably, the most valuable of such cellular tools are stem cells: systems which are naturally primed to form and repair human tissues. However, stem cells are so ripe with potential, being able to differentiate (i.e., gradually transform themselves) into many diverse tissue-specific cell types, that a key challenge in tissue engineering is learning how to direct stem cells to behave in predictable ways. As highlighted in a recent review article by P. Chandra and S.-J. Lee of Wake Forest School of Medicine in Biomarker Insights (DOI: 10.4137/BMI.S20057; p. 105), innovations in biomaterial design and synthesis can play a significant role in enabling improved platforms for stem cell engineering.
An ideal tissue-sculpting biomaterial would be able to mimic natural environmental niches that can coax stem cells into an appropriate series of responses along their tissue formation trajectory. These responses include adhesion, migration, proliferation, and differentiation (see Figure). In practice, designing the right environment is highly challenging, as native niches exhibit chemical, biological, and mechanical elements (e.g., small-molecule growth factors, signaling proteins, and extracellular matrix polymers) that contribute in concerted ways to direct stem cell fate. Progress, however, is being made, and Chandra and Lee survey this progressive research landscape.
Schematic illustration of interactions between endogenous stem cells and synthetic microenvironment. Stem cells’ fate in a particular microenvironment is regulated by intricate reciprocal molecular interactions with its surroundings. Credit: Biomarker Insights.
Specifically, Chandra and Lee’s review overviews and analyzes the results from more than 90 studies in which synthetic biomaterials have been applied to influence stem cell behavior. The authors discuss the roles of salient properties that affect a biomaterial’s performance as an artificial niche, including biocompatibility, drug release behavior, mechanical elasticity, surface chemistry, and surface topography. Current favored materials show promise, but require further optimization. For example, electrospun polymers—such as poly(lactic-co-glycolide)—can be fabricated with tunable growth factor release kinetics, but the nanoscale morphological features of such materials are difficult to control reliably (thus hampering simultaneous control over the role of surface topography on stem cell response).
Due to the extensive combinatorial factors that influence stem cell proliferation and differentiation, the authors call for increased high throughput and computational studies as the field works toward a better understanding of extracellular matrix signals and their roles in controlling stem cell fate. However, despite the many lessons that remain ahead, the union of stem cells and engineered biomaterials holds great promise. Chandra and Lee emphasize this fact as they close their report by highlighting a variety of biomaterial-cell products that are currently under clinical development.
