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Vancomycin-bearing Synthetic Bone Graft Delivers rhBMP-2 and Promotes Healing of Critical Rat Femoral Segmental Defects

  • Basic Research
  • Published:
Clinical Orthopaedics and Related Research®

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.

Questions/purposes

(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.

Clinical Relevance

pHEMA-nHA-vancomycin preabsorbed with rhBMP-2 may be useful in the repair of critical-size long bone defects prone to infections.

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Acknowledgments

The authors thank April Mason-Savas for histology support and Dr. James Potts for discussions on statistical analysis.

Author information

Authors and Affiliations

  1. Department of Orthopedics & Physical Rehabilitation, University of Massachusetts Medical School, 55 Lake Ave. North S4-834, Worcester, MA, USA

    Jordan D. Skelly ME, Jeffrey Lange MD, Tera M. Filion PhD, Xinning Li MD, David C. Ayers MD & Jie Song PhD

  2. Department of Cell & Developmental Biology, University of Massachusetts Medical School, Worcester, MA, USA

    Tera M. Filion PhD & Jie Song PhD

Authors
  1. Jordan D. Skelly ME
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  2. Jeffrey Lange MD
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  3. Tera M. Filion PhD
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  4. Xinning Li MD
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  5. David C. Ayers MD
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  6. Jie Song PhD
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Corresponding author

Correspondence to Jie Song PhD.

Additional information

The institution of all of the authors has received, during the study period, funding from the National Institutes of Health (R01AR055615).

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 or waived approval for the reporting of this investigation and that all investigations were conducted in conformity with ethical principles of research.

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Skelly, J.D., Lange, J., Filion, T.M. et al. Vancomycin-bearing Synthetic Bone Graft Delivers rhBMP-2 and Promotes Healing of Critical Rat Femoral Segmental Defects. Clin Orthop Relat Res 472, 4015–4023 (2014). https://doi.org/10.1007/s11999-014-3841-1

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  • DOI: https://doi.org/10.1007/s11999-014-3841-1

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