Controllable Release Nanocapsmles Immobilized By Amphiphilic Materials For Inducing Stem Cell Differentiation

The success of regenerative tissue medical engineering is inseparable from reliable in vitro stem cell culture,however,it's the key and difficult point to establish controllable stem cell growth and differentiation conditions for artificial implants.The key to solving this problem is to immobilize protein-like cell signal factors on the surface of the material,on the same time,maintain their biological activity and control their release.Herein,we successfully synthesized an amphiphilic graft polymer based on poly-L-lysine(PLL)(OA-PLL-PEG-N3,named OPP),and achieved the surface biological functionalization for polycaprolactone(PCL)electrospun nanofibers based on its hydrophobicity.Finally,we immobilize the pH-responsive nanocapsules on the surface of electrospun nanofibers,and by encapsulating bone morphogenetic protein-2(BMP-2)in nanocapsules,we can realize the controllable release of BMP-2 and the induction of stem cell differentiation.The results show that the synthesized PLL-based amphiphilic graft copolymer can functionalize the PCL surface,for which the static water contact angle proves that the surface has changed from hydrophobic to hydrophilic,and the infrared spectrum shows the presence of azide groups.The surface fluorescence experiment proved that it can immobilize dibenzocyclooctyne(DBCO)modified nanocapsules on the surface,and can stably release BMP-2,thereby inducing rat bone marrow mesenchymal stem cells(BMSCs)to differentiate into osteoblasts.The construction of this method can flexibly select the number of main chains,hydrophobic and hydrophilic side chains of the amphiphilic graft copolymer by optimizing the binding capacity of amphiphilic materials,based on the different surface charges,hydrophilic and hydrophobic properties,and the number of amphiphilic graft copolymers(and structure)of electrospun nanofiber.At the same time,cell signal factors encapsulated nanocapsules can be immobilization to the electrospun nanofiber by chemical coupling to the ends of the hydrophilic side chain without change the properties of the bulk polymer of the electrospun nanofibers,which can fit the need of stem cell differentiation and different tissue microenvironment,realize the controlled release of cell signaling factors and induce stem cell differentiation,treat tissue damage,repair organs,etc.We hope to provide a material selection and surface biofunctionalization method for regenerative tissue medical engineering and in vitro stem cell culture,as well as provide a new idea for the controllable release of cell signaling factors and the induction of stem cell differentiation.