In vivo compatibility and degradation of crosslinked gelatin gels incorporated in knitted Dacron.
Gelatin gels were applied to porous Dacron meshes with the aim of using these gels for local drug delivery. In this article, the biocompatibility and degradation of gelatin gels with different crosslink densities applied in Dacron were studied in vivo by subcutaneous implantation in rats. Dacron discs were treated with carbon dioxide gas plasma to improve hydrophilicity, and subsequently impregnated with gelatin type B. The gelatin samples were crosslinked to different extents using various amounts of water-soluble carbodiimide (EDC) and N-hydroxysuccinimide (NHS). After 6 h, 2, 5, and 10 days, and 3, 6, and 10 weeks of postimplantation, the tissue reactions and biodegradation were studied by light microscopy. The early reaction of macrophages and polymorphonuclear cells to crosslinked gelatin was similar to or milder than Dacron. Giant cell formation was predominantly aimed at Dacron fibers and was markedly reduced in the presence of a crosslinked gelatin coating. At week 10 of implantation, the crosslinked gelatin gels were still present in the Dacron matrix. The gelatin degradation was less for samples with the highest crosslink density. The gelatin gel with the lowest crosslink density showed clear cellular ingrowth, starting after 6 weeks of implantation. The intermediate and high crosslinked gelatin gels showed little or no ingrowth. In these gels, giant cells were involved in the phagocytosis of gelatin parts at week 10. Application of carbodiimide crosslinked gelatin gels in Dacron is suitable for medical applications because of the good biocompatibility of the gels and the possibility of adapting the degradation rate of gelatin to a specific application.
Kuijpers
A J
AJ
Department of Chemical Technology, Institute of Biomedical Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
van Wachem
P B
PB
van Luyn
M J
MJ
Plantinga
J A
JA
Engbers
G H
GH
Krijgsveld
J
J
Zaat
S A
SA
Dankert
J
J
Feijen
J
J
D000588:Amines / Q000737:chemistry; D000818:Animals; D002234:Carbodiimides / Q000737:chemistry; D002245:Carbon Dioxide / Q000737:chemistry; D003432:Cross-Linking Reagents; D016503:Drug Delivery Systems; D005720:Gamma Rays; D005780:Gelatin / Q000737:chemistry*; D005782:Gels / Q000737:chemistry; D007279:Injections, Subcutaneous; D008264:Macrophages / Q000648:ultrastructure; D008297:Male; D008422:Materials Testing; D009132:Muscles / Q000473:pathology; D011093:Polyethylene Terephthalates / Q000737:chemistry*; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar; D013242:Sterilization; D013388:Succinimides / Q000737:chemistry
D000588:Amines; D002234:Carbodiimides; D003432:Cross-Linking Reagents; D005782:Gels; D011093:Polyethylene Terephthalates; D013388:Succinimides; D002245:Carbon Dioxide; D005780:Gelatin; C001426:N-hydroxysuccinimide