2D Nanosilicates for Sustained and Prolong Therapeutic Delivery

Therapeutic delivery remains a significant clinical challenge due to the lack of biomaterials capable of sequestering and delivering biomolecules in a sustained manner over prolonged durations. Here, we present two-dimensional (2D) nanosilicates as a versatile platform for the sustained delivery of various growth factors, promoting stem cell differentiation and angiogenesis. The high surface area and charged properties of nanosilicates enable the prolonged release (>30 days) of therapeutic molecules while maintaining protein conformation and bioavailability. We demonstrate the efficacy of nanosilicates in delivering a range of growth factors, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and bone morphogenetic protein 2 (BMP2). Incorporating pro-angiogenic therapeutics-loaded nanosilicates into polymeric hydrogels stimulates endothelial cell invasion in 3D in vitro angiogenesis models, with invasion controlled by the specific growth factors conjugated to the nanosilicates. Moreover, BMP2 released from nanosilicates maintains high efficacy, enhancing osteogenic differentiation in human mesenchymal stem cells (hMSCs) at lower concentrations compared to exogenous controls. Overall, this work underscores the potential of nanosilicates as a platform technology for non-covalent conjugation and sustained delivery of therapeutic growth factors, offering a promising solution for directing cell functions in regenerative medicine.