Comparison of implantation and cytotoxicity testing for initially toxic biomaterials.
To evaluate the predictive value of cytotoxicity testing, the present study compares the in vivo tissue responses to in vitro cytotoxicity before and after implantation. Material toxicity was caused by addition of the toxic substance Zincdiethyldithiocarbamate (ZDEC) that is used as a standard for in vitro cytotoxicity testing. Polyurethane discs with the addition of 0.5% or 1% ZDEC as well as nontoxic discs were inserted in the abdominal wall of rats for 1 day up to 6 weeks. After explantation the foreign body response was analyzed immunohistochemically. An in vitro reanalysis of the explanted reference materials (RMs) revealed remaining high concentrations of toxic compounds after 1-week implantation, whereas no toxicity was seen after 6 weeks implantation. This was reflected in the foreign body response where a significantly thicker capsule and more inflammatory cells were seen at 1 week for the toxic implants. Over time, with decreasing toxicity, these differences disappeared. Test samples that only were subjected to in vitro extraction with water did not elute toxic compounds to the same extent as the in vivo conditions. It is concluded that many clinically useful implant materials may be unnecessarily rejected due to the results of in vitro tests.
Rosengren
Agneta
A
Lund University, Department of Experimental Research, Malmö University Hospital, S -205 02 Malmö, Sweden.
Faxius
Linda
L
Tanaka
Noriho
N
Watanabe
Mika
M
Bjursten
Lars M
LM
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry* / Q000494:pharmacology; D006224:Cricetinae / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D004050:Ditiocarb / Q000737:chemistry* / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007249:Inflammation; D020128:Inhibitory Concentration 50; D008168:Lung / Q000166:cytology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D011140:Polyurethanes / Q000737:chemistry; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001672:Biocompatible Materials; D002614:Chelating Agents; D003470:Culture Media; D011140:Polyurethanes; D004050:Ditiocarb