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, DMV, MS; David E. Anderson, DVM, MS; James D. Lillich, DVM, MS; Michael D. Apley, DVM, PhD; Peder J. Jensen, DMD; Alexandru S. Biris, PhD
March 2014
American Journal of Veterinary Research

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.