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This improved strength regulates the release of incorporated components and determines the dressing\u2019s replacement schedule. Therefore, due to the lack of comparative knowledge for the cross-linking of carboxymethyl chitosan, gelatin, and polyvinyl alcohol (CMCs-Gel-PVA) wound dressings, this study was designed a systematic comparison of five distinct strategies: chemical cross-linkers\u2014glutaraldehyde (GLU), EDC\/NHS, citric acid (CA), and succinic acid (SA)\u2014alongside a physical freeze-thaw method. Cross-linked wound dressings were fabricated and systematically characterized in terms of surface morphology (SEM), chemical bonding (FTIR), mechanical strength, porosity, biodegradability, fluid absorption, blood compatibility, cytotoxicity, and anti-inflammatory activity. The scaffolds exhibited interconnected pores ranging from 32.07 to 89.12\u00a0\u00b5m. The non-cross-linked sample showed higher porosity, liquid absorption, and degradation rate (90.33 \u00b1 5.17%), which was attributed to its lower mechanical strength. All samples demonstrated good biocompatibility with no significant cytotoxic effects on 3T3 fibroblasts. Tensile strength values ranged from 0.15 to 1.92\u00a0MPa. Glutaraldehyde-crosslinked scaffolds displayed superior mechanical properties suitable for load-bearing wound applications, despite a slight reduction in cell viability (92.59 \u00b1 3.19%), which remained above the accepted clinical biocompatibility threshold. These scaffolds also showed enhanced coagulation activity, whereas citric acid-crosslinked samples exhibited anticoagulant behavior and superior anti-inflammatory potential. In conclusion, this comparative study demonstrates that the choice of cross-linker dictates key functional properties of CMCs-Gel-PVA scaffolds, allowing for the strategic tuning of mechanical strength, degradation rate, hemostatic activity, and anti-inflammatory potential. These tailored\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    characteristics support their further investigation as candidate materials for advanced wound dressing applications. The successful\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    validation of these findings remains a critical next step to fully ascertain the translational potential of this biomaterial platform.\n                  <\/jats:p>","DOI":"10.1177\/08853282261429351","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T11:40:33Z","timestamp":1772192433000},"page":"363-386","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparative analysis of chemical and physical cross-linking strategies for CMCs\/Gelatin\/PVA wound dressings: Balancing mechanical strength with biocompatibility"],"prefix":"10.1177","volume":"41","author":[{"given":"Sahar","family":"Molzemi","sequence":"first","affiliation":[{"name":"Shahid Beheshti University of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8098-1467","authenticated-orcid":false,"given":"Sepehr","family":"Zamani","sequence":"additional","affiliation":[{"name":"Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naimeh","family":"Mahheidari","sequence":"additional","affiliation":[{"name":"Kerman University of Medical Sciences"},{"name":"Universal Scientific Education and Research Network (USERN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6283-8181","authenticated-orcid":false,"given":"Majid","family":"Salehi","sequence":"additional","affiliation":[{"name":"Shahroud University of Medical Sciences"},{"name":"Shahroud University of Medical Sciences and Health Services"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2021.117632"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.reactfunctpolym.2023.105676"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/gels9110890"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.5829\/IJE.2022.35.10A.15"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/polym13121973"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsapm.3c01676"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120109"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/ma14051105"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpolymj.2021.110271"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2020.111806"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpolymj.2021.110711"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/gels9030230"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202308032"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.3c01162"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2016.02.034"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/polym16182679"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/03602559.2012.718400"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.31003"},{"issue":"9","key":"e_1_3_6_20_2","first-page":"1134","article-title":"Injectable multifunctional hydrogel containing sphingosine 1-phosphate and human acellular amniotic membrane for skin wound healing","volume":"27","author":"Doudi S","year":"2024","unstructured":"Doudi S, Kamalabadi-Farahani M, Atashi A, et al. 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