Research on a microsphere-scaffold delivery system with encapsulated BMP-2

In bone tissue engineering, materials such as collagenous bone matrix, collagen and ceramics have been investigated as carriers for bone morphogenetic potein-2 (BMP-2). Among those materials, synthetic calcium phosphate ceramics manufactured from deproteinized bovine bone (DBB) combined with BMP-2 have gained interest widely. Despite BMP-2 was proven efficacy in various dental or medical applications, it is complicated by its short biological half-live, systemic side effects and rapid clearance. Delivery systems that minimize BMP-2 diffusion away from its therapeutic target are desirable not only to enhance bone formation, but also to limit unwanted pathologies. Chitosan(CS) has been widely used for the controlled delivery of proteins in the format of microspheres. Therefore, DBB and chitosan microspheres (CMs) were chosen as carriers for BMP-2 delivery to overcome those disadvantages.

Objectives: The aim was to increase the osteogenic effect of a microsphere-scaffold fabricated from a porous calcium phosphate (DBB) and a biodegradable polymer (CS). The BMP-2 was pre-encapsulated in CMs to control protein release patterns.

Methods: Firstly, both degradable and non-degradable CMs loaded with BMP-2 were prepared by an emulsion-ionic cross-linking method. Secondly, CMs with BMP-2 was embedded into DBB by a dip-coating process. Afterwards, the physical characteristics were observed by XRD,FT-IR and SEM, and the BMP-2 release was investigated, and the proliferation and differentiation of preosteoblastic cell line MC3T3-E1 were estimated.

Results: The results of XRD indicated that the materials have the both pattern of the HA and β-TCP. The SEM images showed a porous structure and the cells attachment growth. In vitro studies indicated the ability of the materials to support growth and osteogenic differentiation of MC3T3-E1. The results of BMP-2 release at 12hr, 1, 3, 7, 14 and 28 days suggested the material decelerated the release of BMP-2.

Conclusion: this novel material is a potential candidate for bone tissue engineering.