Novel lipid-protein-sugar particles (LPSPs) are potentially biocompatible because they are composed of naturally occurring ingredients and their expected tissue dwell times are relatively short. In this research, we used histological sections to study tissue reaction to LPSPs (4.4-microm median diameter) when used for sciatic nerve block in the rat. As a reference, we compared LPSPs to 60-microm median diameter poly(lactic-co-glycolic) acid (PLGA) microspheres (110,000 MW PLGA, glycolic/lactic ratio 65:35). Four days after injection, both particle types produced acute inflammation within the confines of the injectate, inflammation in adjacent tissues, and myotoxicity. Bupivacaine-free particles did not display myotoxicity, and inflammation in adjacent tissues was reduced. At 2 weeks, inflammation from LPSPs had almost disappeared, whereas PLGA microspheres had a foreign-body giant cell reaction until at least 8 weeks after injection. In contrast, 3.6-microm median diameter, 20,000-MW PLGA microspheres produced a primarily histiocytic reaction 2 weeks after injection. In summary, the LPSPs and PLGA microspheres studied herein have excellent biocompatibility, but tissue reaction to the former is of much shorter duration. Myotoxicity and inflammation of surrounding tissue is largely attributed to bupivacaine. Foreign-body giant cells may be attributed to particle size rather than a specific reaction to PLGA.

No abstract

This study evaluates the effect of crushing load on functional recovery of the sciatic nerve. Male Sprague-Dawley rats were divided into five groups: sham operation, resected sciatic nerve, and 100 g (13 mm Hg/mm2), 500 g (50 mm Hg/mm2), and 15,000 g (1,000 mm Hg/mm2) of sciatic crush load (groups 1-5). In groups 3-5, a 5-mm segment of sciatic nerve was crushed for 10 min using a specially designed crushing device. Motor functional recovery was assessed from hind-limb walking tracks by calculating a sciatic functional index. There was no detectable functional deficit in the group receiving sham operations, while the resected sciatic nerve group exhibited complete dysfunction for the full duration of the experiment. All groups subjected to crush exhibited an initial deficit that gradually recovered to normal by day 14 (100-g crush), day 39 (500-g crush), and day 53 (15,000-g crush). Histological changes were also related to the initial crushing load and the length of the recovery period. Results indicate that the crushing device described is able to administer an adjustable, defined crush injury to the rat sciatic nerve, and that the functional deficit resulting from such an injury can be easily monitored with a sciatic functional index. The rate of recovery of crushed nerves was directly related to the initial load. All crushed nerves recovered in this experiment, even after the application of a 15,000-g load for 10 min.