title: PDGF-BB Delays Degeneration of the Intervertebral Discs in a Rabbit Preclinical Model.
abstract: METHODS
  Preclinical animal study.
  
  
  OBJECTIVE
  Determine the in vivo effects of platelet-derived growth factor BB (PDGF-BB) delivered in a thiol-modified hyaluronic acid (TMHA) hydrogel on intervertebral disk (IVD) degeneration.
  
  
  BACKGROUND
  IVD degeneration is a worldwide health concern and remains without an effective treatment. Several in vitro studies have demonstrated the potential of PDGF-BB, a primary component of platelet-rich plasma, as a therapy for IVD degeneration. Our hypotheses were that treatment of injured IVDs with PDGF would inhibit degeneration and that administration of PDGF in a TMHA hydrogel would improve its efficacy.
  
  
  METHODS
  IVD degeneration was induced using the rabbit annular puncture model. Four weeks after injury, IVDs were treated with either PDGF-BB or PDGF-BB delivered within a TMHA hydrogel. The efficacy of treatment was determined using x-ray, MRI, histology, and biomechanical testing.
  
  
  RESULTS
  At 4 weeks after treatment, cell apoptosis and deposition of matrix containing type III collagen a1 (Col3a1) was demonstrated in both the nucleus pulposus and annulus fibrosus, while this was inhibited by PDGF. At 8 weeks after treatment, disc area and MRI indices of injured IVDs treated with PDGF were significantly higher (P < 0.05) than those treated with the TMHA alone. Similarly, degenerative scores for saline- and TMHA-treated IVDs demonstrated significantly more degeneration (P < 0.05) than PDGF-treated IVDs at 8 weeks. Biomechanical assessments found fewer indicators of degeneration in PDGF-TMHA-treated IVDs at both 4 and 8 weeks post-treatment, compared to saline-, TMHA-, and PDGF-only-treated IVDs. Both PDGF- and PDGF-TMHA-treated IVDs also demonstrated a significant increase (P < 0.05) in compressive strength to failure, compared with controls at 8 weeks post-treatment.
  
  
  CONCLUSIONS
  The results of this study suggest that PDGF-BB significantly decreases disc degeneration and when delivered in a TMHA gel scaffold, helps prevent both apoptosis and Col3 matrix production, while maintaining disc structure and biomechanical function.
  
  
  METHODS
  NA.
authors.affiliation: From the UConn Health Center, Department of Orthopaedic Surgery, Farmington, CT.
authors.forename: David N
authors.initials: DN
authors.lastname: Paglia
authors.forename: Hardeep
authors.initials: H
authors.lastname: Singh
authors.forename: Teja
authors.initials: T
authors.lastname: Karukonda
authors.forename: Hicham
authors.initials: H
authors.lastname: Drissi
authors.forename: Isaac L
authors.initials: IL
authors.lastname: Moss
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077214:Becaplermin; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000187:drug effects* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology* / Q000627:therapeutic use*; D011817:Rabbits
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin