Bony engineering using time-release porous scaffolds to provide sustained growth factor delivery

Caroline Szpalski, Phuong D. Nguyen, Cornelia E. Cretiu Vasiliu, Ioana Chesnoiu-Matei, John L. Ricci, Elizabeth Clark, James E. Smay, Stephen M. Warren

Research output: Contribution to journalArticle

Abstract

Microporous scaffolds designed to improve bony repair have had limited success; therefore, we sought to evaluate whether time-released porous scaffolds with or without recombinant bone morphogenetic protein 2 (rhBMP-2) could enhance stem cell osteoinduction. Custom-made 15/85 hydroxyapatite/β- tricalcium phosphate scaffolds were left empty (E) or filled with rhBMP-2 (E+), calcium sulfate (CS), or CS and rhBMP-2 (CS+). All scaffolds were placed in media and weighed daily. Conditioned supernatant was analyzed for rhBMP-2 and then used to feed human adipose-derived mesenchymal stem cells (ASCs). Adipose-derived mesenchymal stem cell ALP activity, OSTERIX expression, and bone nodule formation were determined. E scaffolds retained 97% (SD, 2%) of the initial weight, whereas CS scaffolds had a near-linear 30% (SD, 3%) decrease over 60 days. E+ scaffolds released 155 (SD, 5) ng of rhBMP-2 (77%) by day 2. In contrast, CS+ scaffolds released only 30 (SD, 2) ng (10%) by day 2, and the remaining rhBMP-2 was released over 20 days. Conditioned media from E+ scaffolds stimulated the highest ALP activity and OSTERIX expression in ACSs on day 2. However, after day 6, media from CS+ scaffolds stimulated the highest ALP activity and OSTERIX expression in ASCs. Adipose-derived mesenchymal stem cells exposed to day 8 CS+-conditioned media produced significantly more bone nodules (10.1 [SD, 1.7] nodules per high-power field) than all other scaffolds. Interestingly, day 8 conditioned media from CS scaffolds simulated significantly more bone nodules than either E or E+ scaffold (P < 0.05 for both). Time-released hydroxyapatite/β-tricalcium phosphate porosity provides sustained growth factor release, enhances ASC osteoinduction, and may result in better in vivo bone formation.

Original languageEnglish (US)
Pages (from-to)638-644
Number of pages7
JournalJournal of Craniofacial Surgery
Volume23
Issue number3
DOIs
StatePublished - May 2012

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Keywords

  • Scaffold
  • bone morphogenetic protein
  • bone tissue engineering
  • ceramics
  • cytokines
  • hydroxyapatite tricalcium phosphate
  • substance release

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

Cite this

Szpalski, C., Nguyen, P. D., Cretiu Vasiliu, C. E., Chesnoiu-Matei, I., Ricci, J. L., Clark, E., Smay, J. E., & Warren, S. M. (2012). Bony engineering using time-release porous scaffolds to provide sustained growth factor delivery. Journal of Craniofacial Surgery, 23(3), 638-644. https://doi.org/10.1097/SCS.0b013e31824db8d4