This study investigated whether delayed treatment of spinal cord injury with controlled release of neurotrophin-3 (NT-3) from fibrin scaffolds can stimulate enhanced neural fiber sprouting. Long Evans rats received a T9 dorsal hemisection spinal cord injury. Two weeks later, the injury site was re-exposed, and either a fibrin scaffold alone, a fibrin scaffold containing a heparin-based delivery system with different concentrations of NT-3 (500 and 1,000 ng/mL), or a fibrin scaffold containing 1,000 ng/mL of NT-3 (no delivery system) was implanted into the injury site. The injured spinal cords were evaluated for morphological differences using markers for neurons, astrocytes, and chondroitin sulfate proteoglycans 2 weeks after treatment. The addition of 500 ng/mL of NT-3 with the delivery system resulted in an increase in neural fiber density compared to fibrin alone. These results demonstrate that the controlled release of NT-3 from fibrin scaffolds can enhance neural fiber sprouting even when treatment is delayed 2 weeks following injury. Biotechnol. Bioeng. 2009; 104: 1207-1214. (C) 2009 Wiley Periodicals, Inc.