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

  • Basic Research
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Clinical Orthopaedics and Related Research®

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.

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Acknowledgments

We thank the following members of the RCSI Tissue Engineering Research Group for their input with this project: John M. O’Byrne FRCSI, Cappagh National Orthopaedic Hospital and Royal College of Surgeons in Ireland; Keith A. Synnott FRCSI, Mater Misericordiae University Hospital and University College Dublin; and Hester McAllister MVB and Lynne Hughes MVB, University Veterinary Hospital and University College Dublin.

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Correspondence to Fergal J. O’Brien PhD.

Additional information

One of the authors certifies that he (FGL), or a member of his immediate family, has or may receive payments or benefits, during the study period, an amount of USD (USD 10,000–USD 100,000), from the clinical research PhD fellowship program of the Health Research Board, Irish Government Department of Health, Dublin, Ireland. Authors John P Gleeson and Fergal J O’Brien hold intellectual property with a commercial product related to the collagen-hydroxyapatite scaffold used in this study.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.

Clinical Orthopaedics and Related Research neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use.

Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at the Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland; and the Trinity Centre for Bioengineering, Department of Mechanical Engineering, Trinity College, Dublin, Ireland. Three-dimensional micro-CT reconstruction and analysis were done with assistance from Scanco Medical, Wangen-Brüttisellen, Switzerland.

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Lyons, F.G., Gleeson, J.P., Partap, S. et al. Novel Microhydroxyapatite Particles in a Collagen Scaffold: A Bioactive Bone Void Filler?. Clin Orthop Relat Res 472, 1318–1328 (2014). https://doi.org/10.1007/s11999-013-3438-0

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  • DOI: https://doi.org/10.1007/s11999-013-3438-0

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