Cell-interactive alginate hydrogels for bone tissue engineering.pdf

E. Alsberg1, K.W. Anderson2, A. Albeiruti3, R.T. Franceschi45, and D.J. Mooneyl 3*,6 Departments of Biomedical Engineering, 2Otolaryngology-Head and Neck Surgery, Biologic and Materials Sciences, 4Biological Chemistry, 5Periodontics/Prevention Geriatrics, and 6Chemical Engineering, University of Michigan, Ann Arbor, MI 48109-2136; *corresponding author, Room 5213 Dental School, 10 11 North University, Ann Arbor, MI 48 109- 1078, J Dent Res 80(11 ):2025-2029, 2001 ABSTRACT There is significant interest in the development of injectable carriers for cell transplantation to engi- neer bony tissues. In this study, we hypothesized that adhesion ligands covalently coupled to hydro- gel carriers would allow one to control pre-osteo- blast cell attachment, proliferation, and differen- tiation. Modification of alginate with an RGD- containing peptide promoted osteoblast adhesion and spreading, whereas minimal cell adhesion was observed on unmodified hydrogels. Raising the adhesion ligand density increased osteoblast proli- feration, and a minimum ligand density (1.5-15 femtomoles/cm2) was needed to elicit this effect. MC3T3-E1 cells demonstrated increased osteoblast differentiation with the peptide-modified hydrogels, as confirmed by the up-regulation of bone-specific differentiation markers. Further, transplantation of primary rat calvarial osteoblasts revealed sta- tistically significant increases of in vivo bone for- mation at 16 and 24 weeks with G4RGDY-modified alginate compared with unmodified alginate. These findings demonstrate that biomaterials may be designed to control bone development from transplanted cells. KEY WORDS: osteoblasts, peptide, adhesion ligands, integrins, gene expression. Received January 26, 2001; Last revision September 20, 2001; Accepted September 28, 2001 Cell-interactive Alginate Hydrogels for Bone Tissue Engineering INTRODUCTION T e replacement of bone lost as a result of congenital anomalies, trauma, and disease presents a substantial clini