Soft tissue response to glycerol-suspended controlled-release glass particulate

Vesicoureteral reflux and urinary incontinence have previously been treated by various means including the endoscopic delivery of injectable bulking m aterials such as silicone micro-implants, PTFE implants, glass particles, f at and bovine collagen. These first three materials do not degrade and coll agen requires frequently repeated injections in order to sustain the restor ed continence provided. Vesicoureteric reflux in children usually resolves independently before the age of five. Correction is required before this, b ecause treatment by prophylactic antibiotics is frequently unsuccessful in preventing breakthrough infection. The ideal material for injection should have large particles to avoid migration, inject easily and controllably, be non-toxic and dissolve over the period of time by which time the kidney wi ll be mature. Three different controlled-release glass (CRG) granule compos itions have been prepared by Giltech Ltd, and suspended in a suitable carri er medium (in this case glycerol). The degradable glasses, which have two d ifferent size ranges of 200-300 and <53 mu m, and three different solution rates, were injected intramuscularly into the dorso-lumbar region of rats. Histological analysis of cryostat cut section after time periods of 2 d, 4 and 9 wk, and 6 mon has been performed. Histology sections were stained for neutrophils and macrophages using enzyme histochemistry. ED1 (monocytes an d immature macrophages), ED2 (mature tissue macrophages), CD4 (helper/induc er T-lymphocytes and macrophages), CD8 (suppresser/cytotoxic T-lymphocytes) , Interleukin-1 beta, IL-2 (activated T-lymphocytes), Major Histocompatibil ity Complex (MHC) class II (activated macrophages and activated B-lymphocyt es), alpha-beta (T-lymphocytes) and CD45RA (B lymphocytes) antibodies have beed used to stain immunohistochemically each sample. This study demonstrat es that particulate, degrading glass is stimulating an inflammatory respons e in soft tissue at time periods up to 6 mon. It should be noted that very small particulate, fast degrading glass is leading to tissue necrosis and s hould not be considered further for these applications. However, larger par ticulate, slower degrading materials are demonstrating effective potential for stress incontinence applications. (C) 1998 Kluwer Academic Publishers.