Comparative effect of human and Trypanosoma cruzi calreticulin in wound healing J. Ignacio Arias 1 * , Caroll Sepulveda 1 , Patricia Bravo 1 , Christopher Hamilton-West 1 , Ismael Maldonado 2 and Arturo Ferreira 2 1 Faculty of Veterinary and Animal Science, University of Chile, Santiago, Chile 2 Immunology Disciplinary Programme, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile Abstract In orthopaedics, the use of factors that enhance granulation tissue formation and prevent or delay new bone regeneration is sometimes desirable. Calreticulin (CRT), a unique endoplasmic reticulum luminal Ca 2+ -binding chaperone widely distributed in eukaryotic cells, is involved in many cellular functions. Among them, CRT has an important influence in cutaneous wound healing and diverse processes associated with cutaneous repair, inhibition of angiogenesis, promotion of cell adhesion and antitumour effect. One of the molecules involved in several aspects of the host–parasite interplay is Trypanosoma cruzi calreticulin (TcCRT), which is highly homologous to human calreticulin (HuCRT). Here, recombinant (r)HuCRT and rTcCRT are compared on their abilities to affect fibroblast behaviour in a scratch plate assay, and wound healing in in vivo skin rat models. In molar terms, rTcCRT is three orders of magnitude more efficient than rHuCRT in increasing proliferation and migration of human fibroblasts in vitro. A similar effect was observed in vivo on rat skin wounds and inhibition of bone gap bridging in rabbit unicortical bone osteotomies. Copyright © 2012 John Wiley & Sons, Ltd. Received 28 September 2011; Revised 21 June 2012; Accepted 25 August 2012 Keywords Trypanosoma cruzi; calreticulin; fibroblast; proliferation; migration; cell culture 1. Introduction In orthopaedics the main efforts are focused on achieving the regeneration of bone or joint injuries. However, in veterinary orthopaedics the opposite may be required. This is the case in radius curvus, where ulnar ostectomy is performed to free the proximal end of the ulna from the radial shaft, allowing the normal growth of the radius with the formation of interposed granulation tissue. A similar situation occurs in osteoarthritis in hip dysplasias, where the femoral head and neck are excised to control pain. This is accomplished by means of inducing a fibrous pseudoarthro- sis formation in the coxo-femoral joint, thus effectively functioning as a salvage hip joint (Lippincott, 1992). Therefore, the use of factors that enhance granulation tis- sue formation and avoid or delay new bone bridging is desirable (Arias et al., 2008). Such granulation tissue is normally found during natural skin wound healing (Nguyen et al., 2009) and can be modulated by the admin- istration of different chemical agents (Bae et al., 2005; Okwueze et al., 2007). Found originally in rabbit muscle cells (Ostwald and MacLennan, 1974), calreticulin (CRT) is a unique endoplasmic reticulum (ER) Ca 2+ -binding chaperone widely distrib- uted in eukaryotic cells. It plays a role in many cellular functions, such as lectin-like chaperoning, Ca 2+ storage, and signalling and regulation of gene expression (Michalak et al., 2009). CRT is expressed in different mammalian cells and its extracellular functions, have been tested in several in vivo and in vitro assays, showing that CRT has an impor- tant influence in cutaneous wound healing and diverse processes associated with cutaneous repair (Gold et al., 2006, 2010; Nanney et al., 2008), inhibition of angiogenesis (López et al., 2010; Toledo et al., 2010), promotion of cell adhesion (Papp et al., 2007) and antitumour effects (López et al., 2010; Toledo et al., 2010; Ramírez et al., 2011a). Extracellular biological activities of CRT are mainly related to cellular adhesion, migration and phagocytosis, which are critical aspects of wound healing (Nguyen *Correspondence to: J. Ignacio Arias, Faculty of Veterinary Science, Universidad de Chile, Casilla 2 Correo 15, La Granja, Santiago, Chile. E-mail: joarias@uchile.cl Copyright © 2012 John Wiley & Sons, Ltd. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH ARTICLE J Tissue Eng Regen Med 2015; 9: 41–54. Published online 29 October 2012 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/term.1613