Tissue engineering has appeared in the 1980s. This multidisciplinary ﬁeld is applied in regenerative medicine to help various damaged tissues and organs, and it is based on using of cells, scaffolds, and bioactive factors. Scaffolds not only provide a supportive template for cell attachment, but they also create a biomechanical and physical environment. So the scaffolds play an active role in the regulation of cell behaviors (Qiu 2012). Because of the toxic and inﬂammatory capacity of synthetic polymers, which lead to reducing extracellular matrix (ECM) remodeling and growth capacity, the xeno-or allogeneic tissues are substituted to biodegradable synthetic scaffolds (Thompson 1992). The cells of xeno-or allogeneic tissues as biological scaffolds, are removed, and their ECM remains as 3-dimensioal (3D) structure (Badylak et al. 2009). These natural ECMs decrease immune and inﬂammatory response in grafting through decellularization, and serve as inductive means through their structural and functional proteins and endogenous growth factors (Assmann 2013; Badylak et al. 2012).Collagen, elastin, and various glycosaminoglycans (GAGs), are the main component of biological scaffolds,inwhichcollagenneeds toformstablestructures, then elastin provides elasticity and ﬂexibility of ECM, and eventually, GAGs cause adhesion, migration, proliferation, and differentiation of cells (Jackson et al. (1991); Stringer and Gallagher 1997). Also, bioactive factors that are preserved in biological scaffolds, have an essential role in regulatory signals and functions (Crapo et al. 2011; Gilbert et al. 2006). During the decellularization process and preservation of biological scaffolds, the amount of these elements, especially bioactive factors, may be diminished or led to the inactivation of bioactive factors (Crapo et al. 2011; Gilbert et al. 2006). So using exogenous bioactive factors can improve this deﬁciency. Systematical and local application of exogenous bioactive factors is not suitable options because of the following reasons, including fast diffusion of factors in body ﬂuids, which may create unsatisfactory side effects; rapid clearance of factors from application site and low half-life of them in circulation, which required repeated doses and caused raising remedy cost (Nagase 2007; Moreno 2005; Liu 1994; Ohno 2007). So the researchers come to the point that the loading of exogenous bioactive factors into various scaffolds would be an alternative method (Singh et al. 2008). In this review, we study the useful agents to have an ideal biological scaffold. One of these agents is how to prepare the scaffold, which can be divided into two categories: intrinsic and extrinsic elements. Intrinsic elements including the condition of factors which belong to the ECM itself and should/not should be preserved, and, extrinsic elements consist of various biological and non-biological components that do not belong to the ECM and must be added to or removed from it Fig. 1. Another agent is how to store the scaffold, which includes various methods of shortterm and long-term storages with their own advantages and disadvantages.
The useful agent to have an ideal biological scaffold