Delivery of osteoinductive growth factors from degradable PEG hydrogels influences osteoblast differentiation and mineralization

Degradable poly(ethylene glycol) (PEG) hydrogels with varying mass loss profiles were investigated to assess their applicability as delivery vehicles for osteoinductive growth factors in bone tissue engineering. Protein release is readily controlled by changes in both the structure (i.e., macromer concentration) and chemistry (i.e., number of degradable units) of the starting macromer. In vitro studies indicate an increase in total protein levels, alkaline phosphatase, and mineralization by osteoblasts cultured in the presence of osteoinductive growth factors compared to cells cultured with standard media. When growth factors are delivered from a 25 wt% hydrogel, a significant increase in both alkaline phosphatase and mineralization was seen after 3 weeks of culture over growth factor delivery in a bolus fashion. Additionally, gene expression levels of both osteocalcin and type I collagen were higher at early timepoints when growth factors were released from hydrogels. These results indicate that growth factors remain active after photoencapsulation, that the sustained delivery of growth factors alters various markers of osteoblastic differentiation, and that these networks could be useful as delivery vehicles for growth factors in bone tissue engineering. Finally, ectopic bone formation was present in subcutaneous rat tissue after implantation of hydrogel networks loaded with osteoinductive growth factors. (C) 2002 Elsevier Science B.V. All rights reserved.