Effects of transforming growth factor ?1 released from biodegradable polymer microparticles on marrow stromal osteoblasts cultured on poly(propylene fumarate) substrates
✍ Scribed by Peter, Susan J. ;Lu, Lichun ;Kim, Daniel J. ;Stamatas, Georgios N. ;Miller, Michael J. ;Yaszemski, Michael J. ;Mikos, Antonios G.
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 337 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0021-9304
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✦ Synopsis
Recombinant human transforming growth factor 1 (TGF-1) was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) to create a delivery vehicle for the growth factor. The entrapment efficiency of TGF-1 in the microparticles containing 5% PEG was 40.3 ± 1.2% for a TGF-1 loading density of 6.0 ng/1 mg of microparticles. For the same loading, 17.9 ± 0.6 and 32.1 ± 2.5% of the loaded TGF-1 was released after 1 and 8 days, respectively, followed by a plateau for the remaining 3 weeks. Rat marrow stromal cells showed a dose response to TGF-1 released from the microparticles similar to that of added TGF-1, indicating the activity of TGF-1 was retained during microparticle fabrication and after TGF-1 release. An optimal TGF-1 dosage of 1.0 ng/mL was determined through a 3-day dose response study for maximal alkaline phosphatase (ALP) activity. The TGF-1 released from the microparticles loaded with 6.0 ng TGF-1/1 mg of microparticles for the optimal dosage of TGF-1 enhanced the proliferation and osteoblastic differentiation of marrow stromal cells cultured on poly-(propylene fumarate) substrates. The cells showed significantly increased total cell number, ALP activity, and osteocalcin production with values reaching 138,700 ± 3300 cells/ cm 2 , 22.8 ± 1.5 × 10 -7 mol/min/cell, and 15.9 ± 1.5 × 10 -6 ng/cell, respectively, after 21 days as compared to cells cultured under control conditions without TGF-1. These results suggest that controlled release of TGF-1 from the PLGA/PEG blend microparticles may find applications in modulating cellular response during bone healing at a skeletal defect site.