Recombinant human acidic fibroblast growth factor and fibrin carrier regenerates bone

Bone regeneration promoted by acidic recombinant human fibroblast growth fa ctor (rhFGF-1), rabbit demineralized bone matrix (rDBM), and a fibrin (f) d elivery system was measured in critical-sized defects in rabbits' radii. A unilateral segmental defect 20 mm in length was prepared in radii of 48 ske letally mature New Zealand White rabbits divided equally between 4- and 8-w eek cohorts. The temporal cohorts were divided equally among four treatment groups: rDBM, rDBM/f, rDBM/rhFGF-1/f, and rhFGF-1/f. Data for the fifth gr oup, untreated critical-sized defects, were exploited from previous publish ed reports from this laboratory. In response to experimental treatments, ra diomorphometric and histomorphometric methods were used to derive quantitat ive outcome data that were tested by analysis of variance and post hoc mult iple comparison tests (significance p less than or equal to 0.05). Radiomor phometric data (percentage of radiopacity of defect) were acquired at the d ay of the operation and every 2 weeks thereafter, whereas histomorphometric data (square millimeters of new bone formation) were determined at term. T he objective for the study was to develop candidate bone regenerative thera pies. Therefore, the hypotheses were that experimental treatments would pro mote bone formation within critical-sized defects and that one treatment wo uld be superior to the rest. Testing hypotheses was achieved with quantitat ive methodology, and data were subjected to statistical models. Radiopacity at each 2-week period was greater in treated defects than in untreated cri tical-sized defects. The amount of radiopacity promoted by rDBM/f and rhFGF -1/f at 8 weeks was equivalent and was greater than antecedent times. Histo morphometric data analyses indicated that rDBM/f and rDBM evoked the same q uantity of new bone formation at 4 weeks; by 8 weeks, all treatments except rDBM/f had more new bone within the critical-sized defects in comparison t o untreated defects. That rDBM/f promoted less new bone than rDBM alone may suggest fibrin decreases bone formation, perhaps by impeding local solubil ity of endogenous and rDBM-containing signaling molecules. However, rhFGF-1 /f promoted a significant and unexpected increase in bone formation respons e that could refute the previous notion. In conclusion, the combination of rDBM/rhFGF-1/f may represent a significant, new osteogenic therapeutic regi men. Additional assessments in higher order species must be accomplished to corroborate efficacy.