Human osteoprogenitor bone formation using encapsulated bone morphogenetic protein 2 in porous polymer scaffolds

Yang, Xuebin B., Whitaker, Martin J., Sebald, Walter, Clarke, Nicholas, Howdle, Steven M., Shakesheff, Kevin M. and Oreffo, Richard O.C. (2004) Human osteoprogenitor bone formation using encapsulated bone morphogenetic protein 2 in porous polymer scaffolds. Tissue Engineering, 10 (7), 1037-1045. (doi:10.1089/ten.2004.10.1037).

Abstract

The ability to deliver, over time, biologically active osteogenic growth factors by means of designed scaffolds to sites of tissue regeneration offers tremendous therapeutic opportunities in a variety of musculoskeletal diseases. The aims of this study were to generate porous biodegradable scaffolds encapsulating an osteogenic protein, bone morphogenetic protein 2 (BMP-2), and to examine the ability of the scaffolds to promote human osteoprogenitor differentiation and bone formation in vitro and in vivo. BMP-2-encapsulated poly(DL-lactic acid) (PLA) scaffolds were generated by an innovative supercritical fluid process developed for solvent-sensitive and thermolabile growth factors. BMP-2 released from encapsulated constructs promoted adhesion, migration, expansion, and differentiation of human osteoprogenitor cells on three-dimensional scaffolds. Enhanced matrix synthesis and cell differentiation on growth factor-encapsulated scaffolds was observed after culture in an ex vivo model of bone formation developed on the basis of the chick chorioallantoic membrane model. BMP-2-encapsulated polymer scaffolds showed morphologic evidence of new bone matrix and cartilage formation after subcutaneous implantation and within diffusion chambers implanted into athymic mice as assessed by X-ray analysis and immunocytochemistry. The generation of threedimensional biomimetic structures incorporating osteoinductive factors such as BMP-2 indicates their potential for de novo bone formation that exploits cell–matrix interactions and, significantly, realistic delivery protocols for growth factors in musculoskeletal tissue engineering.

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Contributors

Author: Richard O.C. Oreffo

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