Molecular imprinted macroporous chitosan coated mesoporous silica xerogels for hemorrhage control Chenglong Dai a, b, c , Changsheng Liu a, b, c, * , Jie Wei a, b, c , Hua Hong a, b, c , Qinghui Zhao a, b, c a The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China b Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China c Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China article info Article history: Received 22 April 2010 Accepted 28 June 2010 Available online 24 July 2010 Keywords: Chitosan Silica xerogel Molecular imprinting Hemorrhage control Biocompatibility abstract Efficacious hemostatic agents have significant potential for use in rapid exsanguinating hemorrhage control by emergency medical technician or military medic nowadays. Unfortunately, the topical hemostats currently available in market still have various disadvantages. In this study, a series of mac- roporous chitosan coated mesoporous silica xerogel beads (CSSX) with good biocompatibility were developed. They consisted of mesoporous silica xerogel cores and chitosan layers with macroporous structure by using modified sol-gel process and PEG molecular imprinting technique. The textural properties of the CSSX beads were optimized by in vitro and in vivo evaluation for promoting blood clotting and the results indicated that the prepared CSSX beads can significantly accelerate the contact activation pathway of coagulation cascade and produce desirable hemostasis, with the best efficiency from the CSSX prepared with 2% chitosan and 5% PEG. Furthermore, these CSSX beads were observed to create no exothermic reaction and the subsequential tissue thermal injury by histological examination, and exhibited no obvious cytotoxicity even after 7 days. The results of the present study forward CSSX bead as a safe hemostatic system and present a platform for further optimization studies of materials with enhanced hemostatic capabilities for specific injury types. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction Since the past decades, numerous topical hemostatic agents have been developed to improve survival and reduce the compli- cations of blood loss in the battlefield and civilian severe trauma [1e3]. The ideal topical agents should have the capacity to stop large vessel arterial and venous hemorrhage within minutes, be ready and easy to use with minimal training, lightweight and stable, as well as inexpensive [4,5]. Furthermore, they need to ensure the safety and biocompatibility of the materials, such as non-cytotoxic and non-immunogenic properties. Of these topical hemostats, the HemCon chitosan bandage and QuikClot zeolite powder have been reported effective in reducing or stopping bleeding in many cases, for which application they have FDA approval. However, the existing shortcomings associated with current topical hemostats and higher requirements make them limited in a relatively low efficacy and not able to be applied more extensively. The HemCon Ò bandage (HemCon Medical Technologies, Oregon, USA), a lyophilized chitosan derivative, working through the attraction of the protonated amine groups on chitosan molecules to the negatively-charged residues on red blood cell membranes together with the adsorption of chitosan for fibrinogen and plasma proteins, has been developed in collaboration with the US army and used for local management of bleeding wounds for years. Never- theless, this chitosan-based bandage is not large enough or suffi- ciently flexible to fill large or deep wounds, and works best on flat surfaces of limited areas, which constitutes the main obstacle for its application in severe situations [6]. The Quikclot Ò agent (Z-Medica, Connecticut, USA), an alternative FDA approved topical hemostat, is currently available for use in combat situations and has proved highly efficacious in large traumatic hemorrhage control [7,8]. Data in animal and case reports of patients, however, revealed that the thermal injuries resulting from the exothermic reaction and the poor biodegradability are the great challenges for this zeolite-based absorbent hemostat [9e11]. In order to address the problems associated with the zeolite agent, in our previous study, we have proposed and developed the mesoporous silica xerogels (MSX) for use to staunch bleeding with larger surface area and higher porosity than those of traditional zeolites [12]. Unlike the crystal- line zeolites, these MSX have shown great capacity for water * Corresponding author. P. O. Box 112, 130 Meilong Road, Shanghai, PR China. Tel./fax: þ86 21 64251358. E-mail address: csliu@sh163.net (C. Liu). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2010.06.049 Biomaterials 31 (2010) 7620e7630