Recombinant human acidic fibroblast growth factor and fibrin carrier regenerates bone.

Abstract

Bone regeneration promoted by acidic recombinant human fibroblast growth factor (rhFGF-1), rabbit demineralized bone matrix (rDBM), and a fibrin (f) delivery system was measured in critical-sized defects in rabbits' radii. A unilateral segmental defect 20 mm in length was prepared in radii of 48 skeletally mature New Zealand White rabbits divided equally between 4- and 8-week 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 group, untreated critical-sized defects, were exploited from previous published reports from this laboratory. In response to experimental treatments, radiomorphometric and histomorphometric methods were used to derive quantitative outcome data that were tested by analysis of variance and post hoc multiple comparison tests (significance p </= 0.05). Radiomorphometric data (percentage of radiopacity of defect) were acquired at the day of the operation and every 2 weeks thereafter, whereas histomorphometric data (square millimeters of new bone formation) were determined at term. The objective for the study was to develop candidate bone regenerative therapies. Therefore, the hypotheses were that experimental treatments would promote bone formation within critical-sized defects and that one treatment would be superior to the rest. Testing hypotheses was achieved with quantitative methodology, and data were subjected to statistical models. Radiopacity at each 2-week period was greater in treated defects than in untreated critical-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. Histomorphometric data analyses indicated that rDBM/f and rDBM evoked the same quantity 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 to untreated defects. That rDBM/f promoted less new bone than rDBM alone may suggest fibrin decreases bone formation, perhaps by impeding local solubility of endogenous and rDBM-containing signaling molecules. However, rhFGF-1/f promoted a significant and unexpected increase in bone formation response that could refute the previous notion. In conclusion, the combination of rDBM/rhFGF-1/f may represent a significant, new osteogenic therapeutic regimen. Additional assessments in higher order species must be accomplished to corroborate efficacy.