The use of growth factors in tissue engineering offers an added benefit to cartilage regeneration. Growth factors, such as insulin-like growth factor I (IGF-I), increase cell proliferation and can therefore decrease the time it takes for cartilage tissue to regrow. In this study, IGF-I was released from poly(lactic-co-glycolic) acid (PLGA) scaffolds that were designed to have a decreased burst release often associated with tissue engineering scaffolds. The scaffolds were fabricated from IGF-I-loaded PLGA microspheres by a double emulsion (W1/O/W2) technique. The microspheres were then compressed, sintered at 49°C, and salt leached. The bioactivity of soluble IGF-I was verified after being heat treated at 37, 43, 45, 49, and 60°C. Additionally, the bioactivity of IGF-I was confirmed after being released from the sintered scaffolds. The triphasic release lasted 120 days resulting in 20%, 55% and 25% of the IGF-I being released during days 1-3, 4-58, and 59-120, respectively. Seeding bone marrow cells directly onto the IGF-I loaded scaffolds showed an increase in cell proliferation, based on DNA content, leading to an increased glycosaminoglycan (GAG) production. The present results demonstrated that IGF-I remains active after being incorporated into heat-treated scaffolds, further enhancing tissue regeneration possibilities.