Spray dried hyaluronic acid microparticles for adhesion controlled aggregation and potential stimulation of stem cells

Abstract

Spray-dried microparticles of a derivative of hyaluronic acid (HA) have been engineered to obtain a controlled aggregation with Human Mesenchymal Stem Cells (hMSCs) into 3D constructs. We demonstrated the utility of chemical functionalization of a native constituent of the extracellular matrix to improve processing performances and to control on stem cell adhesion and differentiation. Native hyaluronic acid (HA), cell adhesive peptides (RGD), transforming growth factor β3, dexamethasone are biological agents potentially suitable for chondrogenic stimulation of hMSCS. However unmodified HA suffers of drawbacks in terms of stability and versatility of processing. Functionalization strategies are needed to overcome these drawbacks. In this paper microparticles were produced by spray-drying of an aliphatic and amino functionalized HA derivative. Hydrophobic derivatization of HA allowed the production of microparticles stabilized by physical crosslinking and to load and to control dexamethasone release. The presence of pendant amino groups was exploited to tether cyclic RGD and transforming growth factor β3 via maleimide chemistry; cyRGDC functionalization controlled hMSCs/microparticles aggregation. Chondrogenic potential was preliminary assayed by qualitative immunohistological detection.