Surface-engineering of glycidyl methacrylated dextran/gelatin microcapsules with thermo-responsive poly(N-isopropylacrylamide) gates for controlled delivery of stromal cell-derived factor-1α

In situ tissue engineering has been proposed as a promising method to address the need for the clinical regeneration of a wide variety of damaged tissues. This approach comprises the use of a cell-free instructive scaffold that incorporates and releases topical chemotactic factors to recruit host endogenous stem/progenitor cells for tissue regrowth at the locus of implantation. However, the clinical translation of this concept is hampered when repeated doses of medication must be administrated over an extended period of time. In this study, we designed a delivery platform characterized by microcapsules containing thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm) gates on their outer pore surfaces for the controlled release of stromal cell-derived factor (SDF)-1α, an important chemokine for stem cell recruitment/homing. Double-phase emulsified condensation polymerization was used to prepare interconnected porous glycidyl methacrylated dextran (Dex-GMA)/gelatin microcapsules, and plasma-graft pore-filling polymerization was used to graft PNIPAAm into the surface pores of the microcapsules. The in vitro results showed that the PNIPAAm-grafted microcapsules featured thermo-responsive drug release properties due to the swollen-shrunken property of PNIPAAm gates in response to temperature changes. After subcutaneous implantation, the thermally responsive microcapsules resulted in a more sustained and long-term SDF-1α release compared with those without PNIPAAm-grafting. In the future, this delivery system may have great potential for use in cell recruiting biomaterials for various tissue engineering and regenerative medicine applications.