Abstract
Controlled differentiation of Human mesenchymal stem cells (hMSCs) is required for timely induction of bone growth in implantable biomaterials. Differentiation of hMSCs towards a particular lineage depends upon their microenvironment, which is a complex mixture of various physical, chemical and biological parameters. The role of Bone morphogenic protein (BMP2) in early induction of bone formation is well established. Clinical experience and in vitro study has shown that presentation of this protein in small quantities by surface immobilisation significantly induces osteogenic differentiation compared to large quantities provided in solution. This project focuses on developing and understanding responsive micro/nano porous interfaces which deliver BMP2 in a dose dependent fashion to control osteogenic diffentiation of hMSCs. We hypothesise that use of porous membranes primed with LbL deposition of biomacromolecules such as COL and HA will help in induction of cell attachment and growth whilst controlled and localised delivery of BMP2 released from the layers of these porous constructs will induce sustained differentiation of hMSCs. By controlling pore size of membranes, rate of release of BMP2 can be controlled. We use fluorescently labelled Dextran (Flu-DEX) as model protein to study control release mechanism, which is of similar size to BMP2. Polycarbonate (PC) track etched membranes with various pore sizes were used for LbL assembly of COL/HA/Flu-DEX along with hydrolytically degradable polymer Poly-Beta amino ester (Poly2). Six bilayers were constructed into porous membranes with (COL-Flu-DEX)6 and (Poly2-Flu-DEX)6. Use of hydrolytically degradable polymer significantly enhances release of Flu-DEX compared to control (COL-Flu-DEX)6 assembly. Compared to flat (non porous) surface, release from porous samples maintained a relatively slow and steady release. We are currently investigating release of BMP2 using this approach and their influence on the differentiation of hMSCs in vitro
