Biological activity of rhBMP-2 released from PLGA microspheres.

Human recombinant bone morphogenetic protein-2 (rhBMP-2) has been proven effective in stimulating the regeneration of bone in both skeletal and extraskeletal locations. Through encapsulation within, and release from, biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) microspheres, a proven vehicle for sustained delivery of various proteins, the local concentrations of rhBMP-2 could be maintained at optimal levels to stimulate bone regeneration and remodeling at the site of healing in diverse clinical settings. Thus the purpose of this work was to investigate the encapsulation of rhBMP-2 in PLGA microspheres and its biologic activity upon release. Using in vitro tests in simulated body fluids, the effect of rhBMP-2 released from PLGA microspheres upon osteoblast cell cultures was found to be statistically similar to the effect produced by positive controls consisting of nonencapsulated aqueous rhBMP-2 in simulated body fluids. This clarifies an important step in skeletal tissue engineering strategies aimed at the use of encapsulated rhBMP-2 to stimulate bone regeneration and remodeling.

[1]  V. Rosen,et al.  Recombinant human bone morphogenetic protein-2 induces osteoblastic differentiation in W-20-17 stromal cells. , 1992, Endocrinology.

[2]  M. Lee,et al.  Bone morphogenetic proteins: background and implications for oral reconstruction. A review. , 1997, Journal of clinical periodontology.

[3]  V. Rosen,et al.  Novel regulators of bone formation: molecular clones and activities. , 1988 .

[4]  E. Canalis,et al.  Transforming growth factor beta is a bifunctional regulator of replication and collagen synthesis in osteoblast-enriched cell cultures from fetal rat bone. , 1987, The Journal of biological chemistry.

[5]  V. Rosen,et al.  The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats. , 1992, The Journal of bone and joint surgery. American volume.

[6]  T. K. Hunt,et al.  The future of recombinant growth factors in wound healing. , 1998, American journal of surgery.

[7]  D. Puleo,et al.  In vitro cellular responses to bioerodible particles loaded with recombinant human bone morphogenetic protein-2. , 1998, Journal of biomedical materials research.

[8]  A. Mikos,et al.  Guided tissue fabrication from periosteum using preformed biodegradable polymer scaffolds. , 1999, Biomaterials.

[9]  J. Wozney,et al.  Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin. , 1998, Bone.

[10]  V. Rosen,et al.  Recombinant human bone morphogenetic protein induces bone formation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[11]  A. Reddi,et al.  Role of morphogenetic proteins in skeletal tissue engineering and regeneration , 1998, Nature Biotechnology.

[12]  K. C. Ting,et al.  Microparticles of poly(dl-lactic-co-glycolic acid)/poly(ethylene glycol) blends for controlled drug delivery , 1997 .

[13]  M. Murata,et al.  Carrier-dependency of cellular differentiation induced by bone morphogenetic protein in ectopic sites. , 1998, International journal of oral and maxillofacial surgery.

[14]  T. Spelsberg,et al.  Development and characterization of a conditionally immortalized human fetal osteoblastic cell line , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[15]  Y. Hashizume,et al.  Experimental chronic compression on the spinal cord of the rabbit by ectopic bone formation in the ligamentum flavum with bone morphogenetic protein , 1997, Spinal Cord.

[16]  E. LeGrand.  Preclinical promise of becaplermin (rhPDGF-BB) in wound healing. , 1998, American journal of surgery.

[17]  D R Sumner,et al.  Use of Bone Morphogenetic Protein 2 on Ectopic Porous Coated Implants in the Rat , 1997, Clinical orthopaedics and related research.