(559a) Nanoengineered Biomaterials for Sustained and Prolong Therapeutic Delivery

Therapeutic delivery remains a major clinical challenge due to lack of biomaterials to sequester and deliver biomolecules in sustained manner for prolong duration. Here, we introduce two-dimensional (2D) nanosilicates as a platform technology to sequester and deliver a multitude of growth factors to stimulate stem cell differentiation and angiogenesis. The high surface area and charged characteristics of nanosilicates prolong release (>30 days) of therapeutic molecules. The nanosilicates also show high binding efficacy without altering the protein conformation. Interestingly, nanosilicates can maintain bioavailability compared to exogenously delivered biomolecules. We will illustrate the efficacy of nanosilicates to deliver a range of growth factors including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet derived growth factor (PDGF), or bone morphogenetic protein 2 (BMP2). Incorporation of pro-angiogenic therapeutics-loaded nanosilicates within polymeric hydrogels stimulates endothelial cell invasion in a 3D in vitro models of angiogenesis. The results show that endothelial cell invasion is controlled predominately by the type of growth factors conjugated to the nanosilicates. Moreover, the released BMP2 were able to maintain high efficacy as demonstrated by enhanced osteogenic differentiation in human mesenchymal stem cells (hMSCs) at a lower concentration compared to exogenous control. Overall, this work illustrates the importance of nanosilicates as a platform technology to non-covalently conjugate therapeutic growth factors to direct cell functions.