Investigation of biocompatibility of alpha-tricalcium phosphate: Test for primary cutaneous irritation

Abstract

Objectives. The aim of this study was to determine the irritant properties of alpha-tricalcium phosphate, a new calcium phosphate ceramic material, after single application to intact skin of the rabbit. Methods. As a starting compound for obtaining α-tricalcium phosphate, calcium hydroxyapatite was used, sintered and hot pressed. The material was prepared and tested as solid material and paste. The material was evaluated for primary skin irritation according to the UNI EN ISO 10993-10:2002 /Amd 1:2006 Biological evaluation of medical devices, Part 10: Tests for irritation and delayed-type hypersensitivity. The back of the animals was clipped free of fur and divided into four sites with the same area 24 hours before application of the sample. The material was applied to only two sites; the other two were used as controls. All the sites were covered by gauze and the back of the rabbit was wrapped with a non-occlusive bandage. After 4 hours, the bandage and the test material were removed; 1 hour later the sites were examined for skin irritation and the observation was repeated after 24, 48 and 72 hours. The Score of Primary Irritation (SPI) was calculated for each animal and the Primary Irritation Index (PII) was calculated as the arithmetical mean of SPI values. Results. The PII of the test material resulted 0.0. Conclusion. Based on present results, it can be concluded that the primary skinirritation of alpha-tricalcium phosphate tested can be considered negligible.

Cilj istraživanja: Odrediti iritativna svojstva alfa-trikalcijum fosfara (novorazvijenog biomaterijala na bazi kalcijum fosfatne keramike) u toku njegove jednokratne primene na intaktnu kožu kunica. Materijal i metode: Za dobijanje alfa-trikalcijum fosfara (alfa-TCP) korišćen je kalcijum-hidroksiapatit, koji je sinterovan i toplo presovan. Materijal je pripremljen i testiran u cvrstom obliku i u obliku paste. Prema preporukama međunarodnih standarda za ispitivanje biokompatibilnosti (ISO 10993-10:2002/ Amd 1: 2006 Biološko ispitivanje medicinske opreme, deo 10: testovi iritacije i odložene reakcije hipersenzitivnosti) iritativna svojstva određena su u testu primarne kutane iritacije. Krzno na leđima kunića (novozelanski beli kunići, n=12) obrijano je 24 h pre aplikovanja test materijala, a koža je šematski podeljena u četiri zone. Testirani alfa-TCP je primenjen na samo dva mesta, dok su druga dva mesta na istoj životinji korišćena kao negativne kontrole. Delovi kože tretirani mlečnom kiselinom (98%) korišćeni su kao pozitivna kontrola a posebnu kontrolu je činio tretman Na2HPO4 (korišćen za pripremanje paste), fednokratni kontakt kože i ispitivanog materijala trajao je 4 sata, nakon čega je materijal uklonjen, a 1 sat kasnije, makro-patološki određena je iritacija kože. Ispitivanje iritacije kože ponovljeno je nakon 24h, 48 h i 72 h. Izračunavani su skor primarne kutane iritacije (SPP) i indeks primarne kutane iritacije (PII). Rezultati: Indeks primarne kutane iritacije za alfa-TCP u čvrstom obliku i u obliku paste bio je nula i nije se statistički razlikovao u odnosu na negativnu kontrolu (p gt 0.05). Zaključak: Na osnovu dobijenih rezultata može se zaključiti da novorazvijeni biomaterijal, modifikovani alfa-trikalcijum fosfat, u čvrstom obliku i u obliku paste, ne ispoljava iritirajuća svojstva.