Collagen nanofibril self-assembly on a natural polymeric material for the osteoinduction of stem cells in vitro and biocompatibility in vivo

Abstract

This manuscript reports the characterization of molecularly self-assembled collagen nanofibers on a natural polymeric microporous structure and their ability to support stem cell differentiation in vitro and host tissue response in vivo. Specifically, cellulose acetate (CA) and poly(lactic acid-co-glycolic acid) (PLGA) produced two different microporous structures that were coated with self-assembled type I collagen (PLGAc and CAc). Though the total content of collagen was similar between the two materials after coating, the material chemistries significantly affected the molecular collagen self-assembly resulting in a more biomimetic nanofibrillar D-banding pattern on CA (mean fiber diameter of 80 nm) and a sheet like coating on PLGA (mean fiber diameter of 150 nm). Human mesenchymal stem cells (hMSCs) cultured on CA and CAc showed a significantly higher degree of in vitro osteoblastic progression, in contrast to PLGA and PLGAc. Furthermore, at 2 weeks post subcutaneous implantation, collagen coated CA materials showed increased matrix cellularization and enhanced biocompatibility. At 12 weeks both CA and CAc showed significantly greater matrix cellularity and immune acceptance compared to PLGA. This work illustrates the role of materials chemistry to dictate nanoscale protein assembly and its effect in terms of in vitro stem cell differentiation and in vivo host immune response. We also have proved that inclusion of nanoscale self-assembled ECM components such as collagen can enhance the stem cell inductive capabilities and biocompatibility of hydrophilic natural polymeric materials, making them viable alternatives to widely used synthetic polymers.