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

• Published in: Tissue engineering Vol. 10; no. 7-8; pp. 1037 - 1045
• Main Authors: Yang, Xuebin B, Whitaker, Martin J, Sebald, Walter, Clarke, Nicholas, Howdle, Steven M, Shakesheff, Kevin M, Oreffo, Richard O C
• Format: Journal Article
• Language: English
• Published: United States 01.07.2004
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biomimetic Materials - chemistry; Biomimetic Materials - pharmacology; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - physiology; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - chemistry; Bone Morphogenetic Proteins - pharmacology; Cell Culture Techniques - methods; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cells, Cultured; Coated Materials, Biocompatible - chemistry; Coated Materials, Biocompatible - pharmacology; Extracellular Matrix - chemistry; Extracellular Matrix - physiology; Female; Humans; Lactic Acid - chemistry; Male; Materials Testing; Middle Aged; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - physiology; Osteogenesis - drug effects; Osteogenesis - physiology; Polyesters; Polymers - chemistry; Porosity; Protein Binding; Tissue Engineering - methods; Transforming Growth Factor beta - chemistry; Transforming Growth Factor beta - pharmacology
• ISSN: 1076-3279; 1076-3279
• DOI: 10.1089/1076327041887718

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 three-dimensional 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.