Clinical Orthopaedics and Related Research®

, Volume 472, Issue 4, pp 1318–1328

Novel Microhydroxyapatite Particles in a Collagen Scaffold: A Bioactive Bone Void Filler?

  • Frank G. Lyons
  • John P. Gleeson
  • Sonia Partap
  • Karen Coghlan
  • Fergal J. O’Brien
Basic Research

DOI: 10.1007/s11999-013-3438-0

Cite this article as:
Lyons, F.G., Gleeson, J.P., Partap, S. et al. Clin Orthop Relat Res (2014) 472: 1318. doi:10.1007/s11999-013-3438-0

Abstract

Background

Treatment of segmental bone loss remains a major challenge in orthopaedic surgery. Traditional techniques (eg, autograft) and newer techniques (eg, recombinant human bone morphogenetic protein-2 [rhBMP-2]) have well-established performance limitations and safety concerns respectively. Consequently there is an unmet need for osteoinductive bone graft substitutes that may eliminate or reduce the use of rhBMP-2.

Questions/purposes

Using an established rabbit radius osteotomy defect model with positive (autogenous bone graft) and negative (empty sham) control groups, we asked: (1) whether a collagen-glycosaminoglycan scaffold alone can heal the defect, (2) whether the addition of hydroxyapatite particles to the collagen scaffold promote faster healing, and (3) whether the collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds are able to promote faster healing (by carrying a low dose rhBMP-2).

Methods

A 15-mm transosseous radius defect in 4-month-old skeletally mature New Zealand White rabbits were treated with either collagen-hydroxyapatite or collagen-glycosaminoglycan scaffolds with and without rhBMP-2. Autogenous bone graft served as a positive control. Time-series radiographs at four intervals and postmortem micro-CT and histological analysis at 16 weeks were performed. Qualitative histological analysis of postmortem explants, and qualitative and volumetric 3-D analysis of standard radiographs and micro-CT scans enabled direct comparison of healing between test groups.

Results

Six weeks after implantation the collagen-glycosaminoglycan group had callus occupying greater than ½ the defect, whereas the sham (empty) control defect was still empty and the autogenous bone graft defect was completely filled with unremodeled bone. At 6 weeks, the collagen-hydroxyapatite scaffold groups showed greater defect filling with dense callus compared with the collagen-glycosaminoglycan controls. At 16 weeks, the autogenous bone graft groups showed evidence of early-stage medullary canal formation beginning at the proximal and distal defect borders. The collagen-glycosaminoglycan and collagen-glycosaminoglycan-rhBMP-2 groups had nearly complete medullary canal formation and anatomic healing at 16 weeks. However, collagen-hydroxyapatite-rhBMP-2 scaffolds showed the best levels of healing, exhibiting a dense callus which completely filled the defect.

Conclusions

The collagen-hydroxyapatite scaffold showed comparable healing to the current gold standard of autogenous bone graft. It also performed comparably to collagen-glycosaminoglycan-rhBMP-2, a representative commercial device in current clinical use, but without the cost and safety concerns.

Clinical Relevance

The collagen-glycosaminoglycan scaffold may be suitable for a low load-bearing defect. The collagen-hydroxyapatite scaffold may be suitable for a load-bearing defect. The rhBMP-2 containing collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds may be suitable for established nonunion defects.

Copyright information

© The Association of Bone and Joint Surgeons® 2013

Authors and Affiliations

  • Frank G. Lyons
    • 1
    • 2
    • 3
    • 4
  • John P. Gleeson
    • 1
    • 2
  • Sonia Partap
    • 1
    • 2
  • Karen Coghlan
    • 1
    • 2
    • 5
  • Fergal J. O’Brien
    • 1
    • 2
    • 5
  1. 1.Tissue Engineering Research Group, Department of AnatomyRoyal College of Surgeons in IrelandDublin 2Ireland
  2. 2.Trinity Centre for BioengineeringTrinity College DublinDublin 2Ireland
  3. 3.Cappagh National Orthopaedic HospitalDublinIreland
  4. 4.Mater Misericordiae University HospitalDublinIreland
  5. 5.Advanced Materials and Bioengineering Research (AMBER) CentreRoyal College of Surgeons in Ireland, Trinity College DublinDublinIreland