pHEMA-nHA encapsulation and delivery of vancomycin and rhBMP-2 enhances its role as a bone graft substitute.
BACKGROUND
Bone grafts are widely used in orthopaedic procedures. Autografts are limited by donor site morbidity while allografts are known for considerable infection and failure rates. A synthetic composite bone graft substitute poly(2-hydroxyethyl methacrylate)-nanocrystalline hydroxyapatite (pHEMA-nHA) was previously developed to stably press-fit in and functionally repair critical-sized rat femoral segmental defects when it was preabsorbed with a single low dose of 300 ng recombinant human bone morphogenetic protein-2/7 (rhBMP-2/7).


OBJECTIVE
To facilitate clinical translation of pHEMA-nHA as a synthetic structural bone graft substitute, we examined its ability to encapsulate and release rhBMP-2 and the antibiotic vancomycin.


METHODS
We analyzed the compressive behavior and microstructure of pHEMA-nHA as a function of vancomycin incorporation doses using a dynamic mechanical analyzer and a scanning electron microscope. In vitro release of vancomycin was monitored by ultraviolet-visible spectroscopy. Release of rhBMP-2 from pHEMA-nHA-vancomycin was determined by ELISA. Bioactivity of the released vancomycin and rhBMP-2 was examined by bacterial inhibition and osteogenic transdifferentiation capabilities in cell culture, respectively.


RESULTS
Up to 4.8 wt% of vancomycin was incorporated into pHEMA-nHA without compromising its structural integrity and compressive modulus. Encapsulated vancomycin was released in a dose-dependent and sustained manner in phosphate-buffered saline over 2 weeks, and the released vancomycin inhibited Escherichia coli culture. The pHEMA-nHA-vancomycin composite released preabsorbed rhBMP-2 in a sustained manner over 8 days and locally induced osteogenic transdifferentiation of C2C12 cells in culture.


CONCLUSIONS
pHEMA-nHA can encapsulate and deliver vancomycin and rhBMP-2 in a sustained and localized manner with reduced loading doses.


CONCLUSIONS
The elasticity, osteoconductivity, and rhBMP-2/vancomycin delivery characteristics of pHEMA-nHA may benefit orthopaedic reconstructions or fusions with enhanced safety and efficiency and reduced infection risk.
Department of Orthopedics & Physical Rehabilitation, University of Massachusetts Medical School, 55 Lake Avenue North, S4-834, Worcester, MA 01655, USA.
Xinning
X
Li
Jianwen
J
Xu
Tera M
TM
Filion
David C
DC
Ayers
Jie
J
Song
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry; D018786:Bone Substitutes / Q000737:chemistry*; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D020099:Coated Materials, Biocompatible; D019245:Compressive Strength; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004548:Elasticity; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D006882:Hydroxyapatites / Q000737:chemistry*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis / Q000187:drug effects; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013499:Surface Properties; D013997:Time Factors; D014640:Vancomycin / Q000008:administration & dosage* / Q000737:chemistry
D000900:Anti-Bacterial Agents; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006882:Hydroxyapatites; D011109:Polymethacrylic Acids; D011994:Recombinant Proteins; C583512:poly(2-hydroxyethyl methacrylate)-nanocrystalline hydroxyapatite; D014640:Vancomycin