Editorial Type:
Bone, Joint, and Cartilage

In vivo assessment of a multicomponent and nanostructural polymeric matrix as a delivery system for antimicrobials and bone morphogenetic protein-2 in a unicortical tibial defect in goats

Marjolaine Rousseau Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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 DMV, MS
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David E. Anderson Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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 DVM, MS
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James D. Lillich Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Michael D. Apley Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Peder J. Jensen Orlumet LLC, 2501 Crestwood Rd, Ste 102, North Little Rock, AR 72116.

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Alexandru S. Biris Center for Integrative Nanotechnology Sciences, Department of Systems Engineering, College of Engineering and Information Technology, University of Arkansas, Little Rock, AR 72204.

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DOI:
https://doi.org/10.2460/ajvr.75.3.240
Volume/Issue:
Volume 75: Issue 3
Online Publication Date:
01 Mar 2014
Restricted access
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Abstract

Objective—To determine the response of cortical bone to a multicomponent and nanostructural polymeric matrix as a drug delivery system for enhancing bone healing.

Animals—20 healthy adult crossbred goats.

Procedures—A 3.5-mm-diameter unicortical defect was created in each tibia (day 0), and goats (4 goats/group) were treated as follows: not treated (control group), grafted with the matrix, grafted with antimicrobial (tigecycline and tobramycin)–impregnated matrix, grafted with recombinant human bone morphogenetic protein type 2 (rhBMP-2)–impregnated matrix, or grafted with antimicrobial- and rhBMP-2–impregnated matrix. Elution kinetics of antimicrobials was monitored through plasma concentrations. Bone response was assessed with radiographic scoring (days 1 and 30) and dual-energy x-ray absorptiometry (days 1, 14, and 30). Goats were euthanized on day 30, and histomorphologic analysis was performed. Categorical variables were analyzed with a generalized linear model, and continuous variables were analyzed with an ANOVA.

Results—Plasma antimicrobial concentrations indicated continued release throughout the study. Radiography and dual-energy x-ray absorptiometry did not reveal significant differences among treatments on day 30. Periosteal reactions were significantly greater surrounding bone defects grafted with rhBMP-2–impregnated matrix than those not treated or grafted with matrix or with antimicrobial-impregnated matrix; periosteal reactions were similar in bone defects grafted with rhBMP-2–impregnated matrix and antimicrobial- and rhBMP-2–impregnated matrix.

Conclusions and Clinical Relevance—The matrix served as an antimicrobial delivery system and stimulated bone proliferation when rhBMP-2 was present. Antimicrobial and rhBMP-2 can be used concurrently, but the presence of antimicrobials may affect the performance of rhBMP-2.

Abstract

Objective—To determine the response of cortical bone to a multicomponent and nanostructural polymeric matrix as a drug delivery system for enhancing bone healing.

Animals—20 healthy adult crossbred goats.

Procedures—A 3.5-mm-diameter unicortical defect was created in each tibia (day 0), and goats (4 goats/group) were treated as follows: not treated (control group), grafted with the matrix, grafted with antimicrobial (tigecycline and tobramycin)–impregnated matrix, grafted with recombinant human bone morphogenetic protein type 2 (rhBMP-2)–impregnated matrix, or grafted with antimicrobial- and rhBMP-2–impregnated matrix. Elution kinetics of antimicrobials was monitored through plasma concentrations. Bone response was assessed with radiographic scoring (days 1 and 30) and dual-energy x-ray absorptiometry (days 1, 14, and 30). Goats were euthanized on day 30, and histomorphologic analysis was performed. Categorical variables were analyzed with a generalized linear model, and continuous variables were analyzed with an ANOVA.

Results—Plasma antimicrobial concentrations indicated continued release throughout the study. Radiography and dual-energy x-ray absorptiometry did not reveal significant differences among treatments on day 30. Periosteal reactions were significantly greater surrounding bone defects grafted with rhBMP-2–impregnated matrix than those not treated or grafted with matrix or with antimicrobial-impregnated matrix; periosteal reactions were similar in bone defects grafted with rhBMP-2–impregnated matrix and antimicrobial- and rhBMP-2–impregnated matrix.

Conclusions and Clinical Relevance—The matrix served as an antimicrobial delivery system and stimulated bone proliferation when rhBMP-2 was present. Antimicrobial and rhBMP-2 can be used concurrently, but the presence of antimicrobials may affect the performance of rhBMP-2.

Contributor Notes

Dr. Rousseau's present address is Département de sciences cliniques, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, Canada.

Dr. Anderson's present address is Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

This study was performed at the Ruminant Models Laboratory, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

Supported by the Kansas City Area Life Sciences Institutes Inc, Orlumet LLC, and the US Army Telemedicine and Advanced Technology Research Center.

Presented in part at the American College of Veterinary Surgeons Symposium, Seattle, October 2010.

The authors thank Drs. Brad White and Guy Beauchamp for assistance with statistical analysis, Drs. Sanjeev Narayanan and Carl Myers for assistance with microscopic photography, Dr. Daniel Thomson and Cindy Thomson for assistance with laboratory analysis, and Dr. Fumiya Watanabe for assistance with atomic force microscopy analysis and image processing.

Address correspondence to Dr. Rousseau (marjolaine.rousseau@umontreal.ca).
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Mar 2014

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