Journal of Biomaterials and Nanobiotechnology, 2013, 4, 151-164 doi:10.4236/jbnb.2013.42021 Published Online April 2013 (http://www.scirp.org/journal/jbnb) 151 Engineering Chitosan Using α, -Dicarboxylic Acids—An Approach to Improve the Mechanical Strength and Thermal Stability G. Sailakshmi 1 , Tapas Mitra 1 , Suvro Chatterjee 2 , A. Gnanamani 1* 1 Microbiology Division, CSIR-Central Leather Research Institute, Chennai, India; 2 AU-KBC Research Centre, MIT, Anna Univer- sity, Chennai, India. Email: * gnanamani3@gmail.com Received January 19 th , 2013; revised March 5 th , 2013; accepted April 7 th , 2013 Copyright © 2013 G. Sailakshmi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT The current scenario in tissue engineering research demands materials of requisite properties, viz., high porosity, me- chanical stability, thermal stability, biocompatibility and biodegradability for clinical applications. However, bringing these properties in single biomaterial is a challenging task, which needs intensive research on suitable cross-linking agents. In the present study, 3D scaffold was prepared with above said properties using chitosan and oxalic (O), malonic (M), succinic (S), glutaric (G), adipic (A), pimelic (P), suberic (SU), azelaic (AZ) and sebacic (SE) acid (OMS- GAP-SAS) individually as a non covalent cross-linkers as well as the solvent for chitosan. Assessment on degree of cross-linking, mechanical strength, FT-IR analysis, morphological observation, thermal stability, binding interactions (molecular docking), in vitro biocompatibility and its efficacy as a wound dressing material were performed. Results revealed the degree of cross-linking for OMSGAP-SAS engineered chitosan were in the range between ≈55% - 65% and the biomaterial demonstrated thermal stability more than 300˚C and also exhibited ≥3 - 4 fold increase in mechani- cal strength compared to chitosan alone. The bioinformatics studies evidently proved the chemistry behind the interac- tion of OMSGAP-SAS with chitosan. OMSGAP-SAS played dual role to develop the chitosan biomaterial with above said properties, thus matching the requirements needed for various applications. Keywords: Biomaterial; Chitosan; Cytocompatibility; Dicarboxylic Acid; Mechanical Property 1. Introduction Dicarboxylic acids (DCA) are versatile chemical inter- mediates with different chain length, generally repre- sented as HOOC-(R) n -COOH. These chemical com- pounds are used as raw materials for the preparation of perfumes, polymers, adhesives and macrolide antibiotics for many years and are well known polymer building block [1]. DCA came to research focus because of its re- action capability with amine (-NH 2 ) and hydroxyl (-OH) group containing compounds through amide (-CONH 2 ) and ester linkage (-COOR) as evidenced in polyamides and polyesters preparations [2-5]. However, the said reac- tion requires high temperature (>100˚C), which limits its application for the preparations. Alternatively, activation of -COOH group through carbodiimide and/N-hydroxy- succinimide found suitable for the reactions at ambient temperature, results in the formation of active ester (O- acylisourea) as a highly reactive intermediate, which re- acts with -NH 2 and -OH groups at room temperature. However, the pH dependency, the need for additional steps for purification of the products, the uncontrolled forma- tion of side products, hydrolysis and rearrangement reac- tions are the major limiting factors identified in this pro- cess [6-8]. Hence, DCAs find limited usage in biomaterial/ biopolymer preparations. However, the versatile nature of DCA, if exploited properly, it will solve most of the problems associated with the preparation of biomaterial. Generally, biomaterial are prepared from bio-macro- molecules in the presence of glutaraldehyde [9], and it can easily react with -NH 2 group at room temperature and stabilized the bio-macromolecules with the forma- tion of imine (-C=N) linkage. However, recently, for the biomaterials of high mechanical strength and biocom- patibility, it has been identified that glutaraldehyde is not * Corresponding author. Copyright © 2013 SciRes. JBNB