Multilayered inorganic microparticles for tunable dual growth factor delivery

There is an increasing need to control the type, quantity, and timing of growth factors released during tissue healing. Sophisticated delivery systems offering the ability to deliver multiple growth factors with independently tunable kinetics are highly desirable. Here, a multilayered, mineral coated microparticle (MCMs) platform that can serve as an adaptable dual growth factor delivery system is developed. Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) are bound to the mineral coatings with high binding efficiencies of up to 80%. BMP-2 is firstly bound onto a 1^st mineral coating layer; then VEGF is bound onto a 2^nd mineral coating layer. The release of BMP-2 is sustained over a period of 50 days while the release of VEGF is a typical two-phase release with rapid release in the first 14 days and more sustained release for the following 36 days. Notably, the release behaviors of both growth factors can be independently tailored by changing the intrinsic properties of the mineral coatings. Furthermore, the release of BMP-2 can be tuned by changing the thickness of the 2^nd layer. This injectable microparticle based delivery platform with tunable growth factor release has immense potential for applications in tissue engineering and regenerative medicine. A multilayered, mineral coated microparticle platform is developed for tunable dual growth factor delivery. Distinct release kinetics of BMP-2 and VEGF is achieved by binding the growth factors on different coating layers and manipulating the intrinsic properties of the mineral coatings. This multiple protein delivery system has immense potential in tissue engineering to better mimic the natural healing process.