Abstract
Implants made of poly(lactide-co-glycolide) (PLGA) are biodegradable and frequently provoke foreign body reactions (FBR) in the host tissue. In order to modulate the inflammatory response of the host tissue, PLGA implants can be loaded with anti-inflammatory drugs. The aim of this study was to analyze the impact of PLGA 80/20 rods loaded with the diclofenac sodium (DS) on local tissue reactions in the femur of rats. Special emphasis was put on bone regeneration and the presence of multinucleated giant cells (MGCs) associated with FBR. PLGA 80/20 alone and PLGA 80/20 combined with DS was extruded into rods. PLGA rods loaded with DS (PLGA+DS) were implanted into the femora of 18 rats. Eighteen control rats received unloaded PLGA rods. The follow-up period was of 3, 6 and 12 weeks. Each group comprised of six rats. Peri-implant tissue reactions were histologically and histomorphometrically evaluated. The implantation of PLGA and PLGA+DS8 rods induced the formation of a layer of newly formed bone islands parallel to the contour of the implants. PLGA+DS rods tended to reduce the presence of multi-nucleated giant cells (MGCs) at the implant surface. Although it is known that the systemic administration of DS is associated with compromised bone healing, the local release of DS via PLGA rods did not have negative effects on bone regeneration in the femora of rats throughout 12 weeks.
Highlights
Biocompatible, biostable materials such as metals have been used in traumatology and orthopedic surgery for a long time [1]
PLGA is degraded via a hydrolytic scission of its ester bonds into the monomers, lactic acid (LA) and glycolic acid (GA), which are subsequently metabolized via the tricarboxylic acid (TCA) cycle to generate CO2 and H2O, and some of GA may be excreted in the urine [11,13,16,17]
In rats treated with PLGA implants having no diclofenac sodium (DS), foreign body reactions (FBR) in terms of multi-nucleated giant cells (MGCs) tended to increase over time, whereas in the groups treated with PLGA rods loaded with DS (PLGA+DS), implants, tended to increase over time, whereas in the groups treated with PLGA+DS, implants, Peri-Implant Multinucleated Giant Cells (piMGCs) remained rather constant over the healing period of 12 weeks, which is indicative of an anti-inflammatory effect of DS on the tissues at the implant interface
Summary
Biocompatible, biostable materials such as metals have been used in traumatology and orthopedic surgery for a long time [1]. PLGA is degraded via a hydrolytic scission of its ester bonds into the monomers, lactic acid (LA) and glycolic acid (GA), which are subsequently metabolized via the tricarboxylic acid (TCA) cycle to generate CO2 and H2O, and some of GA may be excreted in the urine [11,13,16,17]. During their degradation process, resulting particles and products lead to the stimulation of the immune system and lead to the development of local chronic inflammation [18,19,20,21]
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