Contents lists available at ScienceDirect Bioactive Materials journal homepage: http://www.keaipublishing.com/biomat Chitosan based bioactive materials in tissue engineering applications-A review Md. Minhajul Islam a , Md. Shahruzzaman a , Shanta Biswas a , Md. Nurus Sakib a , Taslim Ur Rashid a,b,∗ a Department of Applied Chemistry and Chemical Engineering, Faculty of Engineering and Technology, University of Dhaka, Dhaka, 1000, Bangladesh b Fiber and Polymer Science, North Carolina State University, Campus Box 7616, Raleigh, NC, 27695, United States ARTICLEINFO Keywords: Chitosan Bioactive material Scafold Tissue engineering ABSTRACT In recent years, there have been increasingly rapid advances of using bioactive materials in tissue engineering applications. Bioactive materials constitute many diferent structures based upon ceramic, metallic or polymeric materials,andcanelicitspecifctissueresponses.However,mostofthemarerelativelybrittle,stif,anddifcult to form into complex shapes. Hence, there has been a growing demand for preparing materials with tailored physical, biological, and mechanical properties, as well as predictable degradation behavior. Chitosan-based materialshavebeenshowntobeidealbioactivematerialsduetotheiroutstandingpropertiessuchasformability into diferent structures, and fabricability with a wide range of bioactive materials, in addition to their bio- compatibility and biodegradability. This review highlights scientifc fndings concerning the use of innovative chitosan-based bioactive materials in the felds of tissue engineering, with an outlook into their future appli- cations. It also covers latest developments in terms of constituents, fabrication technologies, structural, and bioactive properties of these materials that may represent an efective solution for tissue engineering materials, making them a realistic clinical alternative in the near future. 1. Introduction Recently, biologically-active natural materials have garnered pro- minence to be used as potential materials in tissue engineering due to their unique characteristics. They are capable of imitating the human tissue structure because of their physical and chemical resemblance. It is worth to note that the demand for natural bioactive materials has been increasing over the last two decades because natural polymers are less toxic and more biocompatible compared to most synthetic poly- mers. At present, repairing and regenerating damaged tissue remains a great challenge in clinical settings. Synthesis of newer and robust bio- materials is necessary for rapid advancement of tissue engineering. A number of natural and synthetic materials such as: chitosan, collagen, gelatin (GL), alginate (Alg), silk fbroin, hydroxyapatite (HAp), hya- luronic acid (HA), polyethylene glycol (PEG), polylactic acid (PLA), poly(lactic-co-glycolic) acid (PGLA), and polycaprolactone (PCL) have been used for tissue engineering applications [1–6]. However, due to drawbacks such as uncontrolled degradation, risk of infection, in- sufcient mechanical properties, difculties in bioaccumulation of degradation products, and local acidic environments, these materials still do not meet the requirements for tissue engineering. To overcome these challenges, researchers have developed hybrid biocomposites with superior properties. They combined two or more biopolymers along with inorganic materials to minimize the drawbacks of single- component materials. Among the biopolymers, chitosan has been widely studied as a potential bioactive material because of its unique properties and availability. In recent years, chitosan has been shown to be a promising bioactive material for tissue engineering (bone, skin, cartilage, intervertebral disc, blood vessel, etc.) that can extensively be used for repairing diseased and damaged tissue. Chitosan (CS) is a partially deacetylated form of chitin mainly procured from the exoskeleton of crustaceans [7]. It occupies a distinct position amongst other biomaterials due to its abundance, versatility, and unique properties including biodegradability, biocompatibility, non-toxicity, hydrophilicity, anti-bacterial and anti-fungal properties, and wound-healing efects [8]. In addition, the existence of β-(1,4) glycosidic bonds between D-glucosamine and N-acetyl-D-glucosamine makes chitosan easy to be modifed by chemical reactions with https://doi.org/10.1016/j.bioactmat.2020.01.012 Received 25 October 2019; Received in revised form 29 January 2020; Accepted 31 January 2020 Peer review under responsibility of KeAi Communications Co., Ltd. ∗ Corresponding author. Department of Applied Chemistry and Chemical Engineering, Faculty of Engineering and Technology, University of Dhaka, Dhaka, 1000, Bangladesh. E-mail address: turashid@ncsu.edu (T.U. Rashid). Bioactive Materials 5 (2020) 164–183 2452-199X/ © 2020 Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/). T