Clinical Orthopaedics and Related Research®

, Volume 472, Issue 4, pp 1318–1328

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

Authors

  • Frank G. Lyons
    • Tissue Engineering Research Group, Department of AnatomyRoyal College of Surgeons in Ireland
    • Trinity Centre for BioengineeringTrinity College Dublin
    • Cappagh National Orthopaedic Hospital
    • Mater Misericordiae University Hospital
  • John P. Gleeson
    • Tissue Engineering Research Group, Department of AnatomyRoyal College of Surgeons in Ireland
    • Trinity Centre for BioengineeringTrinity College Dublin
  • Sonia Partap
    • Tissue Engineering Research Group, Department of AnatomyRoyal College of Surgeons in Ireland
    • Trinity Centre for BioengineeringTrinity College Dublin
  • Karen Coghlan
    • Tissue Engineering Research Group, Department of AnatomyRoyal College of Surgeons in Ireland
    • Trinity Centre for BioengineeringTrinity College Dublin
    • Advanced Materials and Bioengineering Research (AMBER) CentreRoyal College of Surgeons in Ireland, Trinity College Dublin
    • Tissue Engineering Research Group, Department of AnatomyRoyal College of Surgeons in Ireland
    • Trinity Centre for BioengineeringTrinity College Dublin
    • Advanced Materials and Bioengineering Research (AMBER) CentreRoyal College of Surgeons in Ireland, Trinity College Dublin
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