Effects of transforming growth factor β1 released from biodegradable polymer microparticles on marrow stromal osteoblasts cultured on poly(propylene fumarate) substrates

Susan J. Peter, Lichun Lu, Daniel J. Kim, Georgios N. Stamatas, Michael J. Miller, Michael J Yaszemski, Antonios G. Mikos

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Recombinant human transforming growth factor β1 (TGF-β1) 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-β1 in the microparticles containing 5% PEG was 40.3 ± 1.2% for a TGF-β1 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-β1 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-β1 released from the microparticles similar to that of added TGF-β1, indicating the activity of TGF-β1 was retained during microparticle fabrication and after TGF-β1 release. An optimal TGF-β1 dosage of 1.0 ng/mL was determined through a 3-day dose response study for maximal alkaline phosphatase (ALP) activity. The TGF-β1 released from the microparticles loaded with 6.0 ng TGF-β1/1 mg of microparticles for the optimal dosage of TGF-β1 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/cm2, 22.8 ± 1.5 x 10-7 μmol/min/cell, and 15.9 ± 1.5 x 10-6 ng/cell, respectively, after 21 days as compared to cells cultured under control conditions without TGF-β1. These results suggest that controlled release of TGF-β1 from the PLGA/PEG blend microparticles may find applications in modulating cellular response during bone healing at a skeletal defect site. (C) 2000 John Wiley and Sons, Inc.

Original languageEnglish (US)
Pages (from-to)452-462
Number of pages11
JournalJournal of Biomedical Materials Research
Volume50
Issue number3
DOIs
StatePublished - 2000

Fingerprint

Biodegradable polymers
Osteoblasts
Transforming Growth Factors
Polypropylenes
Substrates
Polyethylene glycols
glycolic acid
Phosphatases
poly(propylene fumarate)
Intercellular Signaling Peptides and Proteins
Alkaline Phosphatase
Osteocalcin
Acids
Rats

Keywords

  • Biodegradable polymers
  • Bone tissue engineering
  • Growth factor delivery
  • Marrow stromal cells
  • Poly(propylene fumarate)
  • Transforming growth factor β1

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials

Cite this

Effects of transforming growth factor β1 released from biodegradable polymer microparticles on marrow stromal osteoblasts cultured on poly(propylene fumarate) substrates. / Peter, Susan J.; Lu, Lichun; Kim, Daniel J.; Stamatas, Georgios N.; Miller, Michael J.; Yaszemski, Michael J; Mikos, Antonios G.

In: Journal of Biomedical Materials Research, Vol. 50, No. 3, 2000, p. 452-462.

Research output: Contribution to journalArticle

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AB - Recombinant human transforming growth factor β1 (TGF-β1) 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-β1 in the microparticles containing 5% PEG was 40.3 ± 1.2% for a TGF-β1 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-β1 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-β1 released from the microparticles similar to that of added TGF-β1, indicating the activity of TGF-β1 was retained during microparticle fabrication and after TGF-β1 release. An optimal TGF-β1 dosage of 1.0 ng/mL was determined through a 3-day dose response study for maximal alkaline phosphatase (ALP) activity. The TGF-β1 released from the microparticles loaded with 6.0 ng TGF-β1/1 mg of microparticles for the optimal dosage of TGF-β1 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/cm2, 22.8 ± 1.5 x 10-7 μmol/min/cell, and 15.9 ± 1.5 x 10-6 ng/cell, respectively, after 21 days as compared to cells cultured under control conditions without TGF-β1. These results suggest that controlled release of TGF-β1 from the PLGA/PEG blend microparticles may find applications in modulating cellular response during bone healing at a skeletal defect site. (C) 2000 John Wiley and Sons, Inc.

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