Biomaterials 26 (2005) 1211–1218 Variable cytocompatibility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation Christopher G. Williams a,b,1 , Athar N. Malik a,1 , Tae Kyun Kim a,c , Paul N. Manson b , Jennifer H. Elisseeff a, * a Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA b Division of Plastic and Reconstructive Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, MD 21287, USA c Department of Orthopedic Surgery, Seoul National University Bundang Hospital, South Korea Received 29 October 2003; accepted 18 April 2004 Available online 21 July 2004 Abstract The development of biocompatible photopolymerizing polymers for biomedical and tissue engineering applications has the potential to reduce the invasiveness and cost of biomaterial implants designed to repair or augment tissues. However, more information is needed about the cellular toxicity of the compounds and initiators used in these systems. The current study evaluates the cellular toxicity of three ultraviolet sensitive photoinitiators on six different cell populations that are used for engineering numerous tissues. The photoinitiator 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Irgacure 2959) caused minimal toxicity (cell death) over a broad range of mammalian cell types and species. It was also demonstrated that different cell types have variable responses to identical concentrations of the same photoinitiator. While inherent differences in the cell lines may contribute to the variable cytotoxicity, a correlation between cellular proliferation rate (population doubling time) and increased cytotoxicity of the photoinitiator was observed. Cell lines that divided more quickly were more sensitive to photoinitiator- induced cell death. In summary, the photoinitiator Irgacure 2959 is well tolerated by many cell types over a range of mammalian species. Cell photoencapsulation strategies may be optimized to improve cell survival by manipulating proliferation rate. r 2004 Elsevier Ltd. All rights reserved. Keywords: Photopolymerization; Cytotoxicity; Hydrogel; Cell encapsulation; Cell proliferation; Free radical 1. Introduction Photopolymerization is used in a broad range of commercial and biological applications such as printing, dentistry, optical materials [1], encapsulating pancreatic islet cells [2,3], and blood vessel adhesives [4]. These systems are being used for an increasing number of biomedical applications because of their ability to rapidly convert liquid monomer or macromer solutions to a cross-linked network under physiologic conditions [5]. Important advantages of photopolymerizable sys- tems include powerful spatial and temporal control of reactions kinetics, minimal heat production, ability to uniformly encapsulate cells, and significant adaptability for in situ polymerization by adapting light sources to fit clinical scenarios. The development of biocompatible photopolymeriz- able polymers for tissue engineering applications has the potential to reduce the invasiveness and cost of many surgical procedures. For instance, instead of making large incisions to implant cell- and polymer-based therapies, physicians could potentially reduce costs and surgical trauma by injecting and efficiently poly- merizing cells and polymers in situ in tissue defects by minimally invasive procedures. If fully developed into clinical practice, such a strategy could postpone or eliminate the need for more aggressive corrective therapies. Photopolymerization reactions are driven by chemi- cals that produce free radicals when exposed to specific wavelengths of light. A variety of photoinitiators, each ARTICLE IN PRESS *Corresponding author. E-mail address: jhe@bme.jhu.edu (J.H. Elisseeff). 1 Christopher G. Williams and Athar N. Malik contributed equally to this work. 0142-9612/$ - see front matter r 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2004.04.024