The current scenario in tissue engineering research demands materials of requisite properties, viz., high porosity, mechanical 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 mechanical strength compared to chitosan alone. The bioinformatics studies evidently proved the chemistry behind the interaction 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.
 S. Huf, S. K. Gener, T. Hirth, S. Rupp and S. Zibek, “Biotechnological Synthesis of Long-Chain Dicarboxylic Acids as Building Blocks for Polymers,” European Journal of Lipid Science and Technology, Vol. 113, No. 5, 2011, pp. 548-561. doi:10.1002/ejlt.201000112
 S. M. Papkov, R. Langer and A. J. Domb, “Synthesis of Aliphatic Polyesters by Polycondensation Using Inorganic Acid as Catalyst,” Polymers for Advanced Technologies, Vol. 22, No. 5, 2009, pp. 502-511. doi:10.1002/pat.1541
 L. H. Olde Damink, P. J. Dijkstra, M. J. Van Luyn, P. B. Van Wachem, P. Nieuwenhuis and J. Feijen, “CrossLinking of Dermal Sheep Collagen Using a Water-Soluble Carbodiimide,” Biomaterials, Vol. 17, No. 8,1996, pp. 765-773. doi:10.1016/0142-9612(96)81413-X
 F. Everaerts, M. Torrianni, M. Hendriks and J. Feijen, “Biomechanical Properties of Carbodiimide Crosslinked Collagen: Influence of the Formation of Ester Crosslinks,” Journal of Biomedical Materials Research Part A, Vol. 85, No. 2, 2008, pp. 547-555. doi:10.1002/jbm.a.31524
 K. Nam, T. Kimura and A. Kishida, “Controlling Coupling Reaction of EDC and NHS for Preparation of Collagen Gels Using Ethanol/Water Co-Solvents,” Macromolecular Bioscience, Vol. 8, No. 1, 2008, pp. 32-37. doi:10.1002/mabi.200700206
 C. Tual, E. Espuche, M. Escoubes and A. J. Domard, “Transport Properties of Chitosan Membranes: Influence of Crosslinking,” Journal of Polymer Science Part B: Polymer Physics, Vol. 38, No. 11, 2000, pp. 1521-1529. doi:10.1002/(SICI)1099-0488(20000601)38:11<1521::AID-POLB120>3.0.CO;2-#
 C. D. Meyer, C. S. Joiner and J. F. Stoddart, “TemplateDirected Synthesis Employing Reversible Imine Bond Formation,” Chemical Society Reviews, Vol. 36, No. 11, 2007, pp. 1697-1844. doi:10.1039/b513441m
 W. A. Bubnis and C. M. Ofner, “The Determination of ε-Amino Groups in Soluble and Poorly Soluble Proteinaceous Materials by a Spectrophotometric Method Using Trinitrobenzenesulfonic Acid,” Analytical Biochemistry, Vol. 207, No. 1, 1992, pp. 129-133. doi:10.1016/0003-2697(92)90513-7
 G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew, D. S. Goodsell and A. J. Olson, “Autodock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility,” Journal of Computational Chemistry, Vol. 30, No. 16, 2009, pp. 2785-2791. doi:10.1002/jcc.21256
 T. Mossmann, “Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays,” Journal of Immunological Methods, Vol. 65, No. 1-2, 1983, pp. 55-63. doi:10.1016/0022-1759(83)90303-4
 S. E. Kim, Y. W. Cho, E. J. Kang, I. C. Kwon, E. B. Lee, J. H. Kim, H. Chung and S. Y. Jeong, “Three-Dimensional Porous Collagen/Chitosan Complex Sponge for Tissue Engineering,” Fibers and Polymers, Vol. 2, No. 2, 2001, pp. 64-70. doi:10.1007/BF02875260
 Q. X. Li, B. Z. Song, Z. Q. Yang and H. L. Fan, “Electrolytic Conductivity Behaviors and Solution Conformations of Chitosan in Different Acid Solutions,” Carbohydrate Polymers, Vol. 63, No. 2, 2006, pp. 272-282. doi:10.1016/j.carbpol.2005.09.024
 N. B. Milosavljevic, L. M. Kljajevic, I. G. Popovic, J. M. Filipovic and M. T. K. Krusic, “Chitosan, Itaconic Acid and Poly (Vinyl Alcohol) Hybrid Polymer Networks of High Degree of Swelling and Good Mechanical Strength,” Polymer International, Vol. 59, No. 5, 2010, pp. 686-694.
 R. Vijayaraghavan, B. C. Thompson, D. R. MacFarlane, K. Ramadhar, M. Surianarayanan, S. Aishwarya and P. K. Sehgal, “Biocompatibility of Choline Salts as Crosslinking Agents for Collagen Based Biomaterials,” Chemical Communication, Vol. 46, No. 2, 2010, pp. 294-296. doi:10.1039/b910601d
 P. H. Chen, Y. H. Hwang, T. Y. Kuo, F. H. Liu, J. Y. Lai and H. J. Hsieh, “Improvement in the Properties of Chitosan Membranes Using Natural Organic Acid Solutions as Solvents for Chitosan Dissolution,” Journal of Medical and Biological Engineering, Vol. 27, No. 1, 2007, pp. 2328.