Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering

Download
2009-07-01
Yilgor, Pinar
Tuzlakoglu, Kadriye
Reis, Rui L.
Hasırcı, Nesrin
Hasırcı, Vasıf Nejat
The aim of this study was to develop a 3-D construct carrying an inherent sequential growth factor delivery system. Poly(lactic acid-co-glycolic acid) (PLGA) nanocapsules loaded with bone morphogenetic protein BMP-2 and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanocapsules loaded with BIVIP-7 made the early release of BMP-2 and longer term release of BMP-7 possible. 3-D fiber mesh scaffolds were prepared from chitosan and from chitosan-PEO by wet spinning. Chitosan of 4% concentration in 2% acetic acid (CHI4-HAc2) and chitosan (4%) and PEO (2%) in 5% acetic acid (CHI4-PEO2-HAc5) yielded scaffolds with smooth and rough fiber surfaces, respectively. These scaffolds were seeded with rat bone marrow mesenchymal stem cells (MSCs). When there were no nanoparticles the initial differentiation rate was higher on (CHI4-HAc2) scaffolds but by three weeks both the scaffolds had similar alkaline phosphatase (ALP) levels. The cell numbers were also comparable by the end of the third week. Incorporation of nanoparticles into the scaffolds was achieved by two different methods: incorporation within the scaffold fibers (NP-IN) and on the fibers (NP-ON). It was shown that incorporation on the CHI4-HAc2 fibers (NP-ON) prevented the burst release observed with the free nanoparticles, but this did not influence the total amount released in 25 days. However NP-IN for the same fibers revealed a much slower rate of release; ca. 70% released at the end of incubation period. The effect of single, simultaneous and sequential delivery of BMP-2 and BMP-7 from the CHI4-HAc2 scaffolds was studied in vitro using samples prepared with both incorporation methods. The effect of delivered agents was higher with the NP-ON samples. Delivery of BMP-2 alone suppressed cell proliferation while providing higher ALP activity compared to BMP-7. Simultaneous delivery was not particularly effective on cell numbers and ALP activity. The sequential delivery of BMP-2 and BMP-7, on the other hand, led to the highest ALP activity per cell (while suppressing proliferation) indicating the synergistic effect of using both growth factors holds promise for the production of tissue engineered bone.

Suggestions

Sequential BMP-2/BMP-7 delivery from polyester nanocapsules
Yilgor, P.; Hasırcı, Nesrin; Hasırcı, Vasıf Nejat (2010-05-01)
The aim of this study was to develop a nanosized, controlled growth factor release system to incorporate into tissue engineering scaffolds and thus activate the cells seeded in the scaffold. Nanocapsules of poly(lactic acid-co-glycolic acid) (PLGA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) were loaded with the bone morphogenetic proteins BMP-2 and BMP-7, respectively, and with bovine serum albumin (BSA), the model protein. BSA-loading efficiency and release kinetics were used to determine the ...
Effect of scaffold architecture and BMP-2/BMP-7 delivery on in vitro bone regeneration
Yilgor, Pinar; Sousa, Rui A.; Reis, Rui L.; Hasırcı, Nesrin; Hasırcı, Vasıf Nejat (2010-11-01)
The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo conditions through a self-contained growth factor delivery system. A set of nanoparticles providing the release of BMP-2 initially followed by the release of BMP-7 were incorporated in poly(epsilon-caprolactone) scaffolds with different 3-D architectures produced by 3-D plotting and wet spinning. The release patterns were: each growth factor alone, simultaneous, and sequential. The orientation of the fibers did not ...
Sequential growth factor delivery from complexed microspheres for bone tissue engineering
Basmanav, F. Buket; KÖSE, GAMZE; Hasırcı, Vasıf Nejat (2008-11-01)
Aim of the study was to design a 3D tissue-engineering scaffold capable of sequentially delivering two bone morphogenetic proteins (BMP). The novel delivery system consisted of microspheres of polyelectrolyte complexes of poly(4-vinyl pyridine) (P4VN) and alginic acid loaded with the growth factors BMP-2 and BMP-7 which themselves were loaded into the scaffolds constructed of PLGA. Microspheres carrying the growth factors were prepared using polyelectrolyte solutions with different concentrations (4-10%) to...
DEVELOPMENT OF AN INTERFEROMETRIC TECHNIQUE TO BE USED IN MEASURING MICRON LEVEL CLEARANCES FILLED WITH A LUBRICANT
Yildirim, Murat; Dursunkaya, Zafer; Okutucu Özyurt, Hanife Tuba (2009-10-21)
The aim of this study is to develop an interferometric technique to measure micron level clearances occurring in small piston-cylinder arrangements; such as hermetically sealed compressors. A Cartesian model of the piston cylinder arrangement is manufactured and lateral and vertical motions are generated via a step motor, and micrometers, respectively, to simulate the piston motion and the change of clearance during the motion. Experiments are conducted in air and a lubricant. Measurements show the importan...
design and implementation of a two-axes linear positioning system for rapid prototyping applications
Yazıcıoğlu, Faruk; Söylemez, Erses; Department of Mechanical Engineering (2007)
In this study, a two axes linear positioning system for testing and applying different rapid prototyping techniques was designed and manufactured. A cable/ pulley mechanism is utilized in the system for transmitting motion from motors into linear motion. Use of a cable/ pulley mechanism overcomes the problems resulting from the utilization of conventional drive systems like ball screws and decreases the overall cost of the system. The carriage elements of both axes were designed and manufactured by using in...
Citation Formats
P. Yilgor, K. Tuzlakoglu, R. L. Reis, N. Hasırcı, and V. N. Hasırcı, “Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering,” BIOMATERIALS, pp. 3551–3559, 2009, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30656.