Implantation sites

The actual time required for poly-L-lactide implants to be completely absorbed is relatively long, and depends on polymer purity, processing conditions, implant site, and physical dimensions of the implant. For instance, 50—90 mg samples of radiolabeled poly-DL-lactide implanted in the abdominal walls of rats had an absorption time of 1.5 years with metaboHsm resulting primarily from respiratory excretion (24). In contrast, pure poly-L-lactide bone plates attached to sheep femora showed mechanical deterioration, but Httie evidence of significant mass loss even after four years (25). 

Fused Pellets. Another form of an implant is a fused pellet. The pellets may be composed of either the dmg alone, or the dmg fused with cholesterol (29,36), and are formed as small cylinders by melting the dmg and then soHdifying it under pressure. Clinical studies with norethindrone pellets have been in progress for a number of years. Effective rates of release of the dmg from the implantation site were originally difficult to achieve. 

Antibiotic-loaded composites of poly(DL-lactic acid) and hydroxyapatite have been studied as a filler in the repair of bone defects (106). The drug dideoxykanamycin was formulated at 20% by weight in a 50 50 PL A/hydroxyapatite composite. Cyclindrical composites were implanted into the penetrated tibeas of rats. Antibiotic was present at the implantation site at least 8 weeks postimplantation. 

G. C., Resorption rate, route of elimination, and ultrastructure of the implant site of polylactic acid in the abdominal wall of the rat, J. Biomed. Mater. Res., 7, 155, 1973. 

FIGURE 7 Movement of ( HJBCNU-associated radioactivity through rabbit brain. Radioactivity resulting from [ H]BCNU was measured at various distances from the implantation site following implantation of discs described for Fig. 5 into the brains of rabbits. Details of the experimental procedure are described in the text. 

After 7 days, the acute inflammatory response at the implantation site was evaluated. Bisphenol A resulted in a moderate level of irritation at the implantation site and was clearly the least biocompatible test substance. Tyrosine derivatives containing the benzyloxycar-bonyl group caused a slight inflammatory response, while all other tyrosine derivatives produced no abnormal tissue response at all. These observations indicate that tyrosine dipeptide derivatives, even if fully protected, are more biocompatible than BPA, a synthetic diphenol. ... 

Since poly(L-tyrosine) cannot be processed into shaped devices, compressed pellets rather than solvent cast films were used as control implants. Poly(L-tyrosine) formed strikingly yellow, moderately inflamed patches that remained at the implantation site throughout the 1-year study. Contrary to soluble proteins or peptides that ar rapidly degraded by enzymes, implants of conventional poly(L-tyro-sine) were evidently nondegradable over a 1-year period. At wee 56 all poly(L-tyrosine) implants were infiltrated by a moderate n ber of inflammatory cells. 

Advantages All the advantages of matrix dissolution system Removal from implant sites not necessary... 

Fig. 6.11 pCT images of implantation site. Bone defect was filled with newly formed bone after 4 weeks implantation. 

Clinical signs and mortality Macroscopic exam + histo on gross lesions Quantitation of corpa lutea and implantation sites Fetal body weights Fetal abnormalities... 

Yamada, T., Ohsawa, K. and Ohno, H. (1988). The usefulness of alkaline solutions for clearing the uterus and staining implantation sites in rats. Exp. Anim. (Tokyo) 37 325-332. 

Despite the fact that DCE is not spermicidal, a DCE gel composition without N9 showed a pregnancy rate almost equivalent to the commercial control (with 4% N9). Furthermore, the DCE gel with only 2% N9 had the lowest pregnancy rate (and mean number of implantation sites). 

After exposure at 10,000 ppm on days 6 through 15 of gestation, 15 of 25 pregnant female rats had no viable femses or implantation sites on the uterine walld... 

In animals, the frequency of abnormal sperm morphology did not increase significantly over controls in mice exposed to concentrations of 10 ppm hexachlorobutadiene (NIOSH 1981). When mice were exposed to 50 ppm (the only other concentration tested), all animals died during the 5 week post-treatment period. Thus, a reliable NOAEL value for reproductive effects cannot be identified for this study. When rat dams were exposed to vapors of hexachlorobutadiene (up to 15 ppm) during gestation (gestation days 6-20), the mean number of implantation sites, total fetal loss, resorptions and number of live fetuses were comparable to unexposed controls (Saillenfait et al. 1989). 

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