Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 32 3 2026 07 31 Comparative Evaluation of Dicarboxylic Acid Crosslinkers in Tailoring Carboxymethyl Tamarind Gum Hydrogel Films for Wound Healing Applications 405 420 10.34172/ps.43463 EN Vishwajeet Sampatrao Ghorpade https://orcid.org/0000-0002-7324-3666 Remeth Jacky Dias https://orcid.org/0000-0002-8234-9630 Akanksha Vidyadhar Gade https://orcid.org/0009-0001-1124-1809 Sanjay Ankush Salgar https://orcid.org/0009-0007-2297-2387 Sanjay Kumar Banerjee https://orcid.org/0000-0002-0044-0984 Kailas Krishnat Mali https://orcid.org/0000-0002-1789-3592 Journal Article 10.34172/ps.43463 2025 11 05 2026 02 23 Introduction: This research introduces a novel comparative study of maleic acid (MA) and succinic acid (SA) as alternative eco-friendly dicarboxylic acid crosslinkers to the frequently utilized citric acid (CA) for carboxymethyl tamarind gum (CMTG) hydrogel films, specifically for wound healing purposes. The study aimed to enhance the mechanical strength and structural integrity of CMTG hydrogel films while maintaining sustained drug release performance, as compared to the conventional CA-crosslinked hydrogel films. Methods: Hydrogel films were fabricated through an esterification-based crosslinking process using CA, MA, and SA. The resulting films were characterized by ATR-FTIR and thermal analysis, and systematically evaluated for carboxyl content, wettability, tensile strength, porosity, swelling ratio, drug loading and release, protein adsorption, permeability, cytocompatibility, and in vitro wound healing efficacy. Results: ATR-FTIR and thermal analyses confirmed successful ester crosslink formation. MA-crosslinked hydrogels (HM) exhibited the highest carboxyl content (538.4±5.1 mEq/100 g), contact angle (80.76±2.87°), and tensile strength (95.82±1.47 MPa), along with reduced porosity (45.19±0.22%) compared to CA (HC) and SA (HS) hydrogel films. Crosslinking with MA significantly improved film stability and reduced erosion in phosphate buffer (pH 7.4). Although HM showed lower swelling and drug loading than HC, it achieved sustained moxifloxacin release over 24 h. All hydrogels exhibited minimal protein adsorption, favorable water vapor permeability, effective microbial barrier properties, excellent cytocompatibility, and enhanced in vitro wound closure relative to control. Conclusion: Maleic acid serves as a promising green crosslinker for developing mechanically robust, biocompatible, and functionally stable CMTG hydrogel films with strong potential for wound healing applications.