Sustained release of BMP-2 in a lipid-based microtube vehicle.

Sustained release systems have been developed for the use of growth factors in tissue engineering applications. However, many of these systems continue to have limitations associated with low loading efficiencies and reduced biological activity after release. In this paper, we utilized a lipid-based microtube system for the sustained release of BMP-2. The lipid microtubes were fabricated using a self-assembly method, in order to avoid the use of harsh organic solvents that may damage the protein. BMP-2 was loaded into the microtubes by rehydrating dried microtubes in the protein solution. The loading efficiency and release kinetics of BMP-2 in the microtubes were measured using in vitro immunoassays. Loading efficiency was found to be dependent on microtube concentration. The potential for this system to deliver biologically active BMP-2 was assessed using the alkaline phosphatase assay and von Kossa staining on human mesenchymal stem cell cultures. The results demonstrate that the lipid microtube system is able to provide sustained delivery of biologically active BMP-2 and thereby induce osteogenic differentiation.

[1]  Jay R Lieberman,et al.  The role of growth factors in the repair of bone. Biology and clinical applications. , 2002, The Journal of bone and joint surgery. American volume.

[2]  R. Bellamkonda,et al.  Sustained release of plasmid DNA using lipid microtubules and agarose hydrogel. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[3]  T. Sakou Bone morphogenetic proteins: from basic studies to clinical approaches. , 1998, Bone.

[4]  K. Lyons,et al.  Bone morphogenetic protein-2: biology and applications. , 1996, Clinical orthopaedics and related research.

[5]  C. Ooi,et al.  Hydrolytic degradation and drug release properties of ganciclovir-loaded biodegradable microspheres. , 2008, Acta biomaterialia.

[6]  K. Takaoka,et al.  Heparin Potentiates the in Vivo Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2* , 2006, Journal of Biological Chemistry.

[7]  Paul Yager,et al.  Formation of Tubules by a Polymerizable Surfactant , 1984 .

[8]  Zhifeng Xiao,et al.  The effect of crosslinking heparin to demineralized bone matrix on mechanical strength and specific binding to human bone morphogenetic protein-2. , 2008, Biomaterials.

[9]  P. Giannoudis,et al.  Molecular aspects of fracture healing: which are the important molecules? , 2007, Injury.

[10]  Young-tae Kim,et al.  In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury. , 2006, Biomaterials.

[11]  David J Mooney,et al.  Protein-based signaling systems in tissue engineering. , 2003, Current opinion in biotechnology.

[12]  Xiaojun Yu,et al.  Tissue-engineered scaffolds are effective alternatives to autografts for bridging peripheral nerve gaps. , 2003, Tissue engineering.

[13]  K. Anseth,et al.  Heparin functionalized PEG gels that modulate protein adsorption for hMSC adhesion and differentiation. , 2005, Acta biomaterialia.

[14]  S. Feng,et al.  Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles prepared by high pressure homogenization for paclitaxel chemotherapy. , 2007, International journal of pharmaceutics.

[15]  David J Mooney,et al.  Quantitative assessment of scaffold and growth factor‐mediated repair of critically sized bone defects , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[16]  V. Sikavitsas,et al.  Effect of bone extracellular matrix synthesized in vitro on the osteoblastic differentiation of marrow stromal cells. , 2005, Biomaterials.

[17]  B. Spargo,et al.  Controlled release of transforming growth factor-β from lipid-based microcylinders , 1995 .

[18]  R. Bellamkonda,et al.  Lipid-based microtubular drug delivery vehicles. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[19]  R. Levy,et al.  Sustained delivery and expression of DNA encapsulated in polymeric nanoparticles , 2000, Gene Therapy.

[20]  C Vigneron,et al.  Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[21]  S. -. Lee,et al.  Cytokine delivery and tissue engineering. , 2000, Yonsei medical journal.

[22]  Hollinger,et al.  Sustained release emphasizing recombinant human bone morphogenetic protein-2. , 1998, Advanced drug delivery reviews.

[23]  A. Khademhosseini,et al.  Bone regeneration through controlled release of bone morphogenetic protein-2 from 3-D tissue engineered nano-scaffold. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[24]  R. Kamijo,et al.  Sulfated Polysaccharides Enhance the Biological Activities of Bone Morphogenetic Proteins* , 2003, Journal of Biological Chemistry.

[25]  S. Boden The ABCs of BMPs. , 2005, Orthopedic nursing.

[26]  P. Yager,et al.  Zero-order interfacial enzymatic degradation of phospholipid tubules. , 1997, Biophysical journal.

[27]  Heterogeneous and anomalous diffusion inside lipid tubules. , 2007, The journal of physical chemistry. B.

[28]  Yasuhiko Tabata,et al.  Tissue regeneration based on growth factor release. , 2003, Tissue engineering.

[29]  S. Bhang,et al.  Long-term delivery enhances in vivo osteogenic efficacy of bone morphogenetic protein-2 compared to short-term delivery. , 2008, Biochemical and biophysical research communications.