The effect of lysophosphatidic acid using a hydrogel or collagen sponge carrier on bone healing in dogs

Kelly R. Might; Steven A. Martinez; Norman Karin; Genyao Lin; Barbara Tarasevich; Roy R. Pool

doi:10.3415/VCOT-15-08-0137

Veterinary and Comparative Orthopaedics and Traumatology, Table of Contents

Vet Comp Orthop Traumatol 2016; 29(04): 306-313
DOI: 10.3415/VCOT-15-08-0137

Original Research

Schattauer GmbH

The effect of lysophosphatidic acid using a hydrogel or collagen sponge carrier on bone healing in dogs

Kelly R. Might

¹Comparative Orthopedics Research Laboratory, Washington State University, Pullman, WA, USA

⁶Current: Mobile Veterinary Specialist, Austin, TX, USA

,

Steven A. Martinez

¹Comparative Orthopedics Research Laboratory, Washington State University, Pullman, WA, USA

,

Norman Karin

²University of Buffalo, Roswell Park Cancer Institute, Buffalo, NY, USA

,

Genyao Lin

³Solvay, Leetsdale, PA, USA

,

Barbara Tarasevich

⁴Pacific Northwest National Laboratory, Richland, WA, USA

,

Roy R. Pool

⁵Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, Department of Veterinary Pathobiology, College Station, TX, USA

› Author Affiliations

Abstract

Summary

Objectives: The purposes of this study were to determine: 1) the efficacy of polycaprolac-tone-g-polyethylene glycol (PCL-g-PEG) and polylactic-co-glycolic acid (PLGA-g-PEG) hydrogels and an absorbable collagen sponge (ACS) as carriers for lysophosphatidic acid (LPA), 2) the effect of LPA on bone healing in dogs, and 3) the ideal dose of LPA to maximally stimulate bone healing.

Methods: Bilateral ulnar ostectomies were performed on purpose bred dogs. Control defects were filled with a PCL-g-PEG or PLGA-g-PEG hydrogel, or a saline soaked ACS. Contralateral defects were filled with a PCL-g-PEG or PLGA-g-PEG hydrogel, or an ACS with each carrying differing concentrations of an LPA solution. Dual-energy X-ray absorptiometry (DXA) was performed. Total bone area (TBA), mineral density (BMD), and mineral content (BMC) were determined at each time point. Relationships between the effect of treatment over time on TBA, BMC and BMD were determined.

Results: Phase 1 - There was no significant difference in DXA-based TBA (p = 0.09), BMC (p = 0.33), or BMD (p = 0.74) over time between LPA treatments, or between the LPA treated and control groups TBA (p = 0.95), BMC (p = 0.99), or BMD (p = 0.46). Phase 2 - There was no significant difference over time between LPA treatments in DXA-based TBA (p = 0.33), BMC (p = 0.45), or BMD (p = 0.43), or between the LPA treated and control groups TBA (p = 0.94), BMC (p = 0.38), or BMD (p = 0.17). Phase 3 - There was no significant difference over time between LPA treatments in DXA-based TBA (p = 0.78), BMC (p = 0.88), or BMD (p = 0.35), or between the LPA treated and control groups TBA (p = 0.07), BMC (p = 0.85), or BMD (p = 0.06). There was a significant increase in TBA (p <0.0001) and BMC (p = 0.0014), but a significant decrease in BMD (p <0.0001) was noted over time when all groups were combined.

Clinical significance: Although LPA has shown promise as an osteoinductive agent in research, its performance as a bone graft substitute, as utilized in this study, is unsupported. Further studies are necessary to determine the incorporation and elution kinetics of LPA from the PLGA-g-PEG hydrogel and from an ACS. Hydrogels may have clinical applications for delaying or preventing bone formation.

Keywords

Lysophosphatidic acid - hydrogel - polycaprolactone - bone healing - osteogenesis

Full Text

References

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