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Porous implants as drug delivery vehicles to augment host tissue integration

Paul A. Clark^*, Eduardo K. Moioli, D. Rick Sumner and Jeremy J. Mao^,1

^* Department of Neurological Surgery, University of Wisconsin–Madison, Madison, Wisconsin, USA;

Department of Anatomy and Cell Biology, Rush University, Chicago, Illinois, USA; and

Columbia University, College of Dental Medicine, Fu Foundation School of Engineering and Applied Sciences, Department of Biomedical Engineering, New York, New York, USA

¹Correspondence: Columbia University Medical Center, 630 W. 168 St., PH7E—CDM, New York, NY 10032, USA. E-mail: jmao{at}columbia.edu

The common premise of synthetic implants in the restoration of diseased tissues and organs is to use inert and solid materials. Here, a porous titanium implant was fabricated for the delivery of microencapsulated bioactive cues. Control-released transforming growth factor-β1 (TGF-β1) promoted the proliferation and migration of human mesenchymal stem cells into porous implants in vitro. At 4 wk of implantation in the rabbit humerus, control-released TGF-β1 from porous implants significantly increased bone-to-implant contact (BIC) by 96% and bone ingrowth by 50% over placebos. Control-released 100 ng TGF-β1 induced equivalent BIC and bone ingrowth to adsorbed 1 µg TGF-β1, suggesting that controlled release is effective at 10-fold less drug dose than adsorption. Histomorphometry, scanning electron microscopy, and microcomputed tomography showed that control-released TGF-β1 enhanced bone ingrowth in the implant’s pores and surface. These findings suggest that solid prostheses can be transformed into porous implants to serve as drug delivery carriers, from which control-released bioactive cues augment host tissue integration.—Clark, P. A., Moioli, E. K., Sumner, D. R., Mao, J. J. Porous implants as drug delivery vehicles to augment host tissue integration.

Key Words: stem cells • transforming growth factor-β, bone morphogenetic proteins • osteoblasts • wound healing • controlled release