title: Vancomycin-bearing synthetic bone graft delivers rhBMP-2 and promotes healing of critical rat femoral segmental defects.
abstract: BACKGROUND
  Bone grafts simultaneously delivering therapeutic proteins and antibiotics may be valuable in orthopaedic trauma care. Previously, we developed a poly(2-hydroxyethyl methacrylate)-nanocrystalline hydroxyapatite (pHEMA-nHA) synthetic bone graft that, when preabsorbed with 400-ng rhBMP-2/7, facilitated the functional repair of critical-size rat femoral defects. Recently, we showed that pHEMA-nHA effectively retains/releases vancomycin and rhBMP-2 in vitro. The success of such a strategy requires that the incorporation of vancomycin does not compromise the structural integrity of the graft nor its ability to promote bone healing.
  
  
  OBJECTIVE
  (1) To evaluate the ability of pHEMA-nHA-vancomycin composites in combination with 3-µg rhBMP-2 to repair 5 mm rat femoral segmental defects, and (2) To determine if the encapsulated vancomycin impairs the graft/rhBMP-2-assisted bone repair.
  
  
  METHODS
  pHEMA-nHA-vancomycin, pHEMA-nHA, or collagen sponge control with/without 3-µg rhBMP-2 were press-fit in 5 mm femoral defects in SASCO-SD male rats (289-300 g). Histology, microcomputed tomography, and torsion testing were performed on 8- and 12-week explants to evaluate the extent and quality of repair. The effect of vancomycin on the temporal absorption of endogenous BMP-2 and stromal cell-derived factor-1 was evaluated by immunohistochemistry. These factors are important for bone healing initiation and stem cell recruitment, respectively.
  
  
  RESULTS
  Partial bridging of the defect with bony callus by 12 weeks was observed with pHEMA-nHA-vancomycin without rhBMP-2 while full bridging with substantially mineralized callus and partial restoration of torsional strength was achieved with 3-µg rhBMP-2. The presence of vancomycin changed the absorption patterns of endogenous proteins on the grafts, but did not appear to substantially compromise graft healing.
  
  
  CONCLUSIONS
  The composite pHEMA-nHA-vancomycin preabsorbed with 3-µg rhBMP-2 promoted repair of 5 mm rat femoral segmental defects. With the sample sizes applied, vancomycin encapsulation did not appear to have a negative effect on bone healing.
  
  
  CONCLUSIONS
  pHEMA-nHA-vancomycin preabsorbed with rhBMP-2 may be useful in the repair of critical-size long bone defects prone to infections.
authors.affiliation: Department of Orthopedics & Physical Rehabilitation, University of Massachusetts Medical School, 55 Lake Ave. North S4-834, Worcester, MA, USA.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Skelly
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lange
authors.forename: Tera M
authors.initials: TM
authors.lastname: Filion
authors.forename: Xinning
authors.initials: X
authors.lastname: Li
authors.forename: David C
authors.initials: DC
authors.lastname: Ayers
authors.forename: Jie
authors.initials: J
authors.lastname: Song
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000378:metabolism; D018786:Bone Substitutes; D016025:Bone Transplantation / Q000295:instrumentation* / Q000379:methods; D054377:Chemokine CXCL12 / Q000378:metabolism; D020099:Coated Materials, Biocompatible; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D017102:Fracture Healing / Q000187:drug effects*; D006882:Hydroxyapatites / Q000737:chemistry*; D008297:Male; D016348:Osseointegration / Q000187:drug effects; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011474:Prosthesis Design; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors; D054159:Torsion, Mechanical; D014640:Vancomycin / Q000008:administration & dosage*; D055114:X-Ray Microtomography
chemical_list: D000900:Anti-Bacterial Agents; C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D020099:Coated Materials, Biocompatible; D006882:Hydroxyapatites; D011109:Polymethacrylic Acids; D011994:Recombinant Proteins; C583512:poly(2-hydroxyethyl methacrylate)-nanocrystalline hydroxyapatite; D014640:Vancomycin
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