Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration

Currently, functional treatment of fracture non-unions and bone loss remain s a significant challenge in the held of orthopaedic surgery. Tissue engine ering of bone has emerged as a new treatment alternative in bone repair and regeneration. Our approach is to combine a polymeric matrix with a cellula r vehicle for delivery of bone morphogenetic protein-2 (BMP-2), constructed through retroviral gene transfer. The objective of this study is to develo p an osteoinductive, tissue-engineered bone replacement system by culturing BMP-2-producing cells on an osteoinductive, biodegradable, polymeric-ceram ic matrix. The hypothesis is that retroviral gene transfer can be used effe ctively in combination with a biodegradable matrix to promote bone formatio n. First, we examined the in vitro attachment and growth of transfected BMP -producing cells on a PLAGA-HA scaffold. Second, the bioactivity of the pro duced BM P in vitro was evaluated using a mouse model. It was found that th e polymer-ceramic scaffold supported BMP-2 production, allowing the attachm ent and growth of retroviral transfected, BMP-2-producing cells. In vivo, t he scaffold successfully functioned as a delivery vehicle for bioactive BMP -2, as it induced heterotopic bone formation in a SCID mouse model. (C) 200 1 Elsevier Science Ltd. All rights reserved.