R. Abundo
Assistant Professor in Periodontology - University of Turin (S.Luigi Gonzaga Hospital - Orbassano) - A.P.O.R. Cultural Secretary

G. Corrente
Assistant Professor in Periodontal Surgery - University of Turin (S.Luigi Gonzaga Hospital - Orbassano)

Evolution of the concept of perimplantary bone regeneration: a molecular approach using bone morphogenetic proteins (BMP).

Thanks to osteointegrated implantology techniques, the clinical setting has continuously evolved along the past fifteen years, and increasing numbers of patients can now be rehabilitated with the application of fixed dental prosthesis even in cases when only movable devices were formerly applicable.

The increasing favour of such practice is essentially due to the existing possibility of obtaining satisfactory bone regeneration whenever needed. Optimal conditions for implant insertion are thus achieved even in cases where it would not have been possible, because of scarcity of the bone substance remaining after loss of tooth elements formerly present in that site.

Several methodologies have been proposed, either alone or in combination, such as surgical application of membranes (reabsorbable or not) and bone grafting (autologous, homologous, heterologous, synthetic).

Such techniques are fundamentally based on two principles: creating and maintaining a space in which bone regeneration will occur, and favouring the formation of a stable blood clot within this space.

Following the biological principles established by Murray and Coll, Hurley and Coll, Melcher and Dryer in the orthopedic area of research during the 50's-60's (1) (2) (3) (4), Nyman (5) was the first in 1982 to apply in the parodontology field the principle of a mechanical barrier by means of membranes, which should favour the migration of selected cells within the regeneration space, thereby preventing repopulation by unwanted cells.

At the beginning of the 90's, several authors proposed GoreTex membrane application as a means of favouring bone regeneration at the implantation sites (6) (7) (8) (9) (10).

The greatest problem encountered with this technique was the difficulty in keeping the so-called "tent effect" by the membrane alone. To accomplish this task, supporting structures and titanium microscrews (11) (12) (13) (14) were employed, or grafting materials (22) (30) (32) (41) were inserted under the barrier devices (15) (16) (17).

Simion et al (18) were the first to show that vertical additions of periimplantary bone crest could be obtained with the use of titanium-reinforced GoreTex membranes; similar results were recently demonstrated by Corrente et al (19) at both clinical and histologic level, with the use of coral-derived calcium carbonate and fibrin glue in the absence of membranes. It was thus confirmed that keeping a space for bone regeneration and stabilizing the blood clot, rather than forming a mechanical barrier, represent the key elements in bone neogenesis.

On the other hand, none of the above mentioned techniques has a clearcut osteoinductive character, i.e. they are not able per se to actively stimulate new bone formation, with the partial exception of autologous bone and, although it is not universally accepted, of lyophilized demineralized human bone. In these cases, the possible osteoinduction activity is linked to the presence of bone morphogenetic proteins (BMP), a family of 13 proteins which are capable of stimulating the neogenesis of bone as it usually occurs following skeletal bone fracture (20).

Using molecular biology techniques, it was possible to isolate and clone the gene responsible for BMP synthesis, and to insert this gene in host cells (generally bacteria) which were thus able to synthesize rh-BMP (recombinant human BMP) in the desired amount.

Once the bacterial product was shown to be non-toxic (21), animal studies were performed in order to evaluate its effectiveness (22-25).

The rh-BMP-2 is currently the most widely tested rh-BMP. In 1991, Torium et al (23) produced bilateral bone defects having a critical dimension of 3 cm (which were thus potentially uncurable by themselves) in dog mandible: On each side, the two mandibular segments were kept separated and in their original location by titanium plaques. In a split-mouth drawing included in the study, rh-BMP-2 was shown to produce complete clinical and histological curing, whereas a placebo substance used as control had no bone regeneration effect.

In a study by Howell et al (24), rh-BMP-2 was equally effective compared to control substances, in forming new bone tissue in contact with implants within 21 days.

Nevins et al (25) confirmed the positive effects of rh-BMP-2 in a model of mascellary sinus augmentation in goat.

Recently, a preliminary report on the tolerance and effectiveness of rh-BMP-2 in humans showed similar results to those reported on animal models (26).

Thanks to this molecular approach, a wholly new horizon has appeared in the area of bone regeneration (27).

This tecnique has notable advantages, among others:

• there is no more need for supplementary devices (membranes, bone grafts, fixation screws to obtain the regeneration of bone), resulting in an undoubted simplification and higher predictiveness of the technique
• the intrinsic regeneration potential of bone can be exploited, thereby reducing the time needed for healing and maturation of neoformed bone.

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