Biomaterials 24 (2003) 1613–1620 An initial investigation of photocurable three-dimensional lactic acid based scaffolds in a critical-sized cranial defect Jason A. Burdick a , Daniel Frankel b , William S. Dernell b , Kristi S. Anseth a,c, * a Department of Chemical Engineering, University of Colorado, Campus Box 424, Engineering Center, ECCH 111, Boulder, CO 80309-0424, USA b Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University VTH, Ft. Collins, CO 80523, USA c Howard Hughes Medical Institute, University of Colorado, Campus Box 424, Engineering Center, ECCH 111, Boulder, CO 80309-0424, USA Received 18 June 2002; accepted 17 October 2002 Abstract Degradable polymer networks formed by the photoinitiated polymerization of multifunctional monomers have great potential as in situ forming materials, especially for bone tissue engineering. In this study, one specific chemistry was analyzed with respect to bone formation in a critical-sized defect model with and without adsorbed osteoinductive growth factors present. The scaffolds degraded in B8 months and possessed an elastic modulus similar to that of trabecular bone. A porous scaffold fabricated with B80% porosity and pore diameters ranging from 45 to 150 mm was implanted in a critical-sized cranial defect in rats. When implanted alone, the scaffolds were filled primarily with fibrous tissue after 9 weeks with only mild inflammation at the defect site. When the scaffolds released osteoinductive growth factors, statistically more bone filled the scaffold. For instance, 65.879.4% (n ¼ 5) of the defects were filled with radiopaque tissue in the osteoinductive releasing scaffolds, whereas only 24.277.4% (n ¼ 5) of the defects were filled in the untreated defects 9 weeks after implantation. These results illustrate not only the benefits of delivering osteoinductive factors when developing synthetic bone grafts, but the potential of these materials for supporting the infiltration and development of bone in large defects. r 2002 Elsevier Science Ltd. All rights reserved. Keywords: Bone tissue engineering; Photopolymerization; Cranial defect; Degradable polymer; In situ forming; Scaffolds 1. Introduction Tissue engineering is emerging as a technique that could potentially be used in the future to develop synthetic bone graft replacement materials for the treatment of large bone defects. While bone grafting is one of the most common and successful clinical treatment options, there are still many limitations. With autografts, the amount of bone available for harvest is limited, and the harvesting procedure may require a second surgery and induce morbity at the tissue donation site [1]. While allografts circumvent these problems, higher failure rates are observed with allografts and associated with decreased integration of the donated tissue and increased potential for rejection [1]. With tissue engineered grafts, the appropriate signals (e.g., osteoconductive surface, growth factors, and osteoprogenitor cells) can be delivered in a controlled fashion and hopefully overcome many of the limitations in current grafting treatments [2,3]. Many approaches are being investigated for tissue engineering and, specifically, for bone tissue engineering. Our group is interested in the development of in situ forming materials that are easily implanted by a surgeon, able to fill irregularly shaped defects, and provide good contact between the implant and the native tissue. In particular, photopolymerization pro- vides control over the polymerization exotherm (i.e., temperature rise) [4], which can minimize tissue necrosis due to excessive temperature increases; spatial control during polymerization allowing the fabri- cation of complex structures; and a mechanism to polymerize multifunctional monomers under physiolo- gical conditions (i.e., body temperature and in the presence of body fluids) [5] for the in vivo formation of biomaterials. *Corresponding author. Tel.: +1-303-492-3147; fax: +1-303-492- 4341. E-mail address: kristi.anseth@colorado.edu (K.S. Anseth). 0142-9612/03/$ - see front matter r 2002 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0142-9612(02)00538-0