Calcitonin as an anticalcification treatment for implantable biological tissues

Abstract

Background and aim of the study: Calcification remains the major role of failure of implantable biomedical material and in particular of bioprosthetic valves. Various treatments have been proposed to mitigate calcification of glutaraldehyde-fixed bioprosthetic valves but none have succeeded in inhibiting or mitigating efficiently the calcification process of the implantable biological tissues. Since the discovery of calcitonin (CT) and its therapeutic role in treating hypercalcemic patients, CT has never been tried as an anticalcification treatment for biomaterials. It is postulated, that tissue calcification may be efficiently minimized by forming adducts with aldehyde groups thus eliminating the places of the biological tissues onto the calcium cations could be deposited.

Material and methods: Fresh porcine aortic leaflets were cut radially in three parts. Three groups of tissue were created. Group I (glutaraldehyde only), Group II (glutaraldehyde with 1% CT) and Group III (glutaraldehyde with 10% CT). All tissues were then implanted subdermally in three sets of 8 (Group I) and 9 (Group II and Group III) male Wistar rats of 12 days old. 21 days later the rats were euthanized by inhalation of CO₂. The tissues were retrieved and after rinsing with distilled water 3 times, were lyophilized at -40°C at high vacuum pressure of approximately 100mmHg for 16h. The calcium content was then measured with flat atomic absorption technique.

Results: The preimplantation values of Ca concentration as expressed in mg Ca/g of tissue were 1.79±0.14 in Group I, 4.78±0.0079 in Group II and 2.88±0.17 in Group III (p=ns). 21 days later the values of Ca concentration were 126.95±12.97 for Group I, 24.69±2.71 for Group II (p<0.05) and 27.16±2.95 for Group III (p<0.05). There was not significance difference between Groups II and III, even if Group II showed a less accumulation of Ca concentration (×5.16) than Group III (×9.43).

Conclusion: An anticalcification treatment based on calcitonin as an additive to buffered glutaraldehyde, mitigates the calcification process of the implantable biological tissues, as compared to glutaraldehyde treatment only.

Keywords: Anticalcification treatment; Bioprosthetic valves; Calcitonin.