255 Effect of titanium implants on primary mineralization following 6 and 14 days of rat tibia1 healing D. Kohavi*, Z. Schwartzt, D. AmW, C. Muller Mai”, U. Gross” and 1. Selas :Oral I&/ant Center and Departments of Prosthodontics; ‘Periodontics; $ Orthopaedic Surgery and h Division of Oral Pathology, The Hebrew University, Hadassah-School of Dental Medicine POE 7 172 Jerusalem 91010, Israel; “Department of Pathology, Free University of Berlin, Hindenburgdam 30 D-1000 Berlin 45, Germany The effect of pure commercial titanium implants on the process of primary mineralization was studied. This was examined by insertion of titanium implants into rat tibia1 bone after ablation. The effects of the titanium were studied through the behaviour of extracellular matrix vesicles (MV). Methods of morphometric analysis at the TEM level were applied. The insertion of titanium implants was followed by an increase in the number of MV as well as vesicular diameter and by a decrease in vesicular distance from the calcified front when compared to normal healing. These results suggest that the process of MV maturation around titanium implants was delayed when compared to normal primary bone formation during bone healing. The delay in mineralization was compensated by an increase in vesicle production, resulting in an enhancement of primary mineralization by the titanium. Keywords: Titanium, bone, calcification Received 10 March 1991; revised 2 May 1991; accepted 20 June 1991 Direct structural and functional bonding between living bone and the surface of a load-carrying implant have been recognized as an important contribution to their successful acceptancel. Several materials demonstrated direct bonding to bone, among them, glass ceramics2-5 and titanium’. Titanium manifested a number of properties which have contributed to its increased use as an orthopaedic and dental implant material. Titanium showed a high corrosion resistance, it is lighter than steel and it can be easily prepared in any required form. Numerous investigators have confirmed the high tissue tolerance of titanium7-“. The stable form of titanium at physiological pH is titanium oxide. This oxide spontaneously forms a thin (5-100 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA A) coherent filmlo. It has been reported in both in viva and in vitro studies that released metal oxides have an inhibitory effect on matrix maturation and primary mineralization in chondroid or osteoid tissues37 *I*‘-16. The direct contact between bone and the implant material is formed during primary mineralization around the implant. Primary mineralization is characterized by the occurrence of extracellular matrix vesicles in cartilage, bone and dentine as proven Correspondence to Professor J. Sela. by ultrastructural and biochemical methods’7-22. It is suggested that matrix vesicles (MV) are produced by blebbing of confined membranal parts of osteoblast to mediate primary mineralization in the extracellular matrix of healing bone. Using morphometric analysis the hypothesis on the maturation of matrix vesicles was suggested as follows: The secretion of an electron lucent vesicle by the cell is followed by its loading with calcium and phosphate. Then, the formation of a calcifying focus on the inner membranal surface is completed by the formation of an hydroxyapatite crystal. Further crystal growth results in the rupture of the vesicular membrane. Adherence of hydroxyapatite crystals to each other results in formation of calcospheritic structures and calcifying frontsz3. Vesicular type, number, size and distance from the calcified front were recently studied in the model of primary mineralization during tibia1 bone healing using a computerized morphometric systemz3. ‘*. The maturation of calcification via extracellular matrix vesicles on each day is accompanied by increase in the vesicular diameter and its approximation to the calcified front. The introduction of glass ceramic implants into the tibia1 rat bones was followed by an increase in the vesicular number and retardation of 0 1992 Butterworth-Heinemann Ltd Biomaterials 1992, Vol. 13 No. 4 0142-9612/92/040255-06