Spatiotemporally Programmed Release of Aptamer Tethered Dual Angiogenic Growth Factors

Abstract

In tissue extracellular matrix (ECM), multiple growth factors (GFs) are sequestered through affinity interactions and released as needed by proteases, establishing spatial morphogen gradients in a time-controlled manner to guide cell behavior. Inspired by these ECM characteristics, we developed an intelligent biomaterial platform that spatially controls the combined bioavailability of multiple angiogenic GFs, specifically vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-BB). Utilizing aptamer affinity interactions and complementary sequences within a GelMA matrix, our platform achieves on-demand, triggered release of individual GFs which can be programmed in temporally-controlled, repeatable cycles. The platform features stable incorporation of dual aptamers specific for both GFs, functional aptamer-CS molecular recognition in a 3D microenvironment with long-term stability of at least 15 days at physiological temperature, and spatially localized sequestration of individual GFs. Additionally, the system allows differential amounts of GFs to be released from the same hydrogels at different time-points, mimicking dynamic GF presentation in a 3D matrix similar to the native ECM. This flexible control over individual GF release kinetics opens new possibilities for dynamic GF presentation, with adjustable release profiles to meet the spatiotemporal needs of growing engineered tissue.