Design of growth factor sequestering biomaterials

Abstract

Growth factors (GFs) are major regulatory proteins that can govern cell fate, migration, and organization. Numerous aspects of the cell milieu can modulate cell responses to GFs, and GF regulation is often achieved by the native extracellular matrix (ECM). For example, the ECM can sequester GFs and thereby control GF bioavailability. In addition, GFs can exert distinct effects depending on whether they are sequestered in solution, at two-dimensional interfaces, or within three-dimensional matrices. Understanding how the context of GF sequestering impacts cell function in the native ECM can instruct the design of soluble or insoluble GF sequestering moieties, which can then be used in a variety of bioengineering applications. This Feature Article provides an overview of the natural mechanisms of GF sequestering in the cell milieu, and reviews the recent bioengineering approaches that have sequestered GFs to modulate cell function. Results to date demonstrate that the cell response to GF sequestering depends on the affinity of the sequestering interaction, the spatial proximity of sequestering in relation to cells, the source of the GF (supplemented or endogenous), and the phase of the sequestering moiety (soluble or insoluble). We highlight the importance of context for the future design of biomaterials that can leverage endogenous molecules in the cell milieu and mitigate the need for supplemented factors.

Hydrogels for therapeutic cardiovascular angiogenesis

“…Understanding the duality of the ECM's role in binding cells and liberating sequestered growth factors is crucial for designing instructive bioactive materials that effectively guide tissue morphogenesis [8]. In angiogenesis, there are several ECM componentsboth soluble and insoluble -that are capable of binding angiogenic growth factors such as VEGF and liberating them in response to cell-mediated enzymatic degradation of the ECM [9]. The exact role of growth factor binding motifs and the liberation of growth factors in this process is highly complex and variable, involving the formation of gradients in vivo that can guide directional sprouting of new vessels [10]].…”

Mechanotransduction and Growth Factor Signalling to Engineer Cellular Microenvironments

“…This approach has been called in some papers affinity-based systems. [26][27][28] In addition, these systems allow presentation of GFs that can be further internalized following receptor binding. [29,30] Seeking to engineer localized GFs reservoirs, layer-by-layer (LbL) assemblies of polyelectrolytes, which alternate positive and negative charged macromolecules have been used.…”

Taking cues from the extracellular matrix to design bone-mimetic regenerative scaffolds

“…Mechanisms for rVEGF delivery have largely centered on either hydrogel vehicles or physical adsorption to various scaffolds [9,152]. CaPs with adsorbed rVEGF have been tested in multiple bone defect models for angiogenic and osteogenic potential [153–155].…”