The Biocompatibility of Vancomycin Containing PLLA/β -TCP Composite and Its Role in Implant Related Osteomyelitis

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Authors: Korkusuz F, Kankilic B, Korkusuz P, Dagdeviren S, Bayramli E, Kilic E, Bilgic E.
Hacettepe University,  Altındag Turkey

Title: The Biocompatibility of Vancomycin Containing PLLA/β -TCP Composite and Its Role in Implant Related Osteomyelitis

Background: Osteomyelitis caused by MRSA often requires surgery and systemic antibiotic treatment. Recently, the disease is treated with local antibiotic delivery systems.

Hypothesis/Purpose: A vancomycin containing poly-l-lactic acid/β-tricalcium phosphate (PLLA/β-TCP) composite was developed and characterized and asked whether these composite was biocompatible and control implant related osteomyelitis.

Methods: Vancomycin-containing (VC) and vancomycin-free (VUC) composites were produced using PLLA, β-TCP and chloroform. Some of the VC composites were further dip-coated with PLLA (CVC) to delay the release of antibiotic. Vancomycin release was studied. Adhesion, proliferation and mineralization were assessed with mesenchymal stem (MSC) and Saos type 2 cells. Later, VUC, VC, and CVC were implanted into implant related osteomyelitis (IRO) sites. Radiology, histology, and microbiology findings were quantified.

Results: VC and CVC released 100% and 63.1% of their vancomycin on day 1. At the end of 6 weeks, CVC released 91.9 % of its vancomycin. For antimicrobial susceptibility test, zones between 10 to 11 mm were considered intermediate and those that were 12 mm or greater were considered sensitive to MRSA. The CVC, VC, and control groups developed 11 mm, 17 mm, and 18 mm inhibition zone diameters, respectively. MSC and Saos type 2 cells attached and proliferated well on composites on days 3 and 7. IRO resolved in the VC group but not in the VUC group. Microbiology, radiology and histology scores of the VC and CVC groups improved by week 6.

Discussion: In the conventional IRO therapy, antibiotics should be given parentally for 4-6 weeks. CVC released its vancomycin for 42 days. On the other hand, VC burst all the vancomycin entrapped in day 1 but IRO was still controlled according to the results. Radiological scores correlated with histological scores and improvement was achieved in the VC. Histological findings with the VC and CVC presented favorable biocompatibility. Microbiologic findings revealed control with the VC and CVC groups.

Conclusion: Vancomycin-containing PLLA/β-TCP composites are biocompatible and control IRO.