Albumin-derived nanoparticles: A flexible biointerface for enhanced adhesion, spatial guidance and growth factor stimulation of human mesenchymal stem cells.

摘要

Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into a variety of cell types and have been widely investigated as a possible alternative treatment strategy for wound healing. A major challenge to the direct application of MSCs in severe wounds is the limited engraftment of these cells at the wound sites (<1%) and a lack of spatial control of MSC adhesion and activation, which could be potentially enhanced through engineered nanoscale multifunctional substrates. The use of human albumin-derived nanoparticles (ANPs) as a foundational nanoscale substrate to display RGD-containing fibronectin FIII9-10 fragment (Abbreviated: Fnf) has been previously reported in the Moghe laboratory. When presented in 2-D cell cultures on ANPs, this ligand has been proven to promote cell motility and extracellular matrix assembly. Here we showed Fnf-ANPs promoted human MSCs (hMSCs) adhesion as well as integrin clustering in cell protrusions and were able to spatially direct the adhesion and growth of hMSC on 2-D polymer substrates. Furthermore, hMSC morphology and its organization of focal adhesion were sensitively modulated by nanoscale size of ANPs. The adhesion of hMSC was cooperatively promoted in the presence of Fnf-ANPs and growth factor, bFGF. In order to promote similar synergies between the biofunctionalized ANPs and growth factors, we engineered albumin nanoparticles with P14 peptide, a fibronectin-derived growth factor sequestering peptide proven to bind to a variety of growth factors. Thus, we demonstrate that albumin-derived nanoparticles can be used as a flexible system for nanoscale presentation of adhesion and growth factors, the combination of which could potentially control hMSC phenotype and functions.