{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:12:59Z","timestamp":1788952379315,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Development and Utilization of Raw and Auxiliary Materials for Biopharmaceuticals","award":["2023RC-Union-4"],"award-info":[{"award-number":["2023RC-Union-4"]}]},{"name":"Inner Mongolia Normal University","award":["2025YJRC137"],"award-info":[{"award-number":["2025YJRC137"]}]},{"award":["2025YJRC137"],"award-info":[{"award-number":["2025YJRC137"]}],"id":[{"id":"https:\/\/ror.org\/0497ase59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>The escalating production of fetal bovine serum generates substantial quantities of fetal bovine hide as an underutilized byproduct. In this study, we extracted collagen from this source, characterized it as predominantly type I collagen with intact triple-helical features, and fabricated a series of composite sponge dressings by blending it with chitosan. The best-balanced formulation (COL1\/CS1, 1:1 ratio) exhibited markedly superior physicochemical properties relative to pure collagen sponges, as evidenced by higher porosity (91.3%), water uptake (2010%), moisture retention (23.7%), and water vapor transmission rate (4169.02 \u00b1 86.45 g\/m2\/day). We hypothesize that the intrinsically lower cross-linking density of fetal collagen may expose a greater abundance of carboxyl and hydroxyl moieties, thereby fostering electrostatic complexation and hydrogen bonding with chitosan\u2019s amino groups. This molecular interplay appears to promote the genesis of a highly uniform, interconnective porous network. In vitro, the COL1\/CS1 sponge elicited a hemolysis rate below 5%, a blood coagulation index as low as 7.02%, no cytotoxicity toward L929 and MRC-5 cells, and a pronounced capacity to stimulate cell proliferation and wound repopulation. In a murine full-thickness excisional wound model, the COL1\/CS1 group achieved a 98.1% closure rate by day 14, significantly outpacing both the pure collagen and untreated controls. Histological examinations corroborated these findings, revealing accelerated granulation tissue deposition, robust neovascularization, and orderly collagen remodeling, with no overt toxicity observed in vital organs under the tested conditions. This work presents a viable valorization pathway for an agricultural byproduct into high-value biomedical constructs and provides insights into how source-dependent collagen attributes may influence the functional performance of biomaterials.<\/jats:p>","DOI":"10.3390\/polym18182198","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:19:16Z","timestamp":1788949156000},"page":"2198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fetal Bovine Hide Collagen\u2013Chitosan Composite Sponges: Preparation, Physicochemical Profiling, and Cutaneous Wound Healing Efficacy"],"prefix":"10.3390","volume":"18","author":[{"given":"Linying","family":"Ni","sequence":"first","affiliation":[{"name":"College of Life Science and Technology, Inner Mongolia Normal University, Hohhot 010022, China"},{"name":"Key Laboratory of Biodiversity Conservation and Sustainable Utilization in Mongolian Plateau for College and University of Inner Mongolia Autonomous Region, Hohhot 010022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Xinxing","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Inner Mongolia Normal University, Hohhot 010022, China"},{"name":"Key Laboratory of Biodiversity Conservation and Sustainable Utilization in Mongolian Plateau for College and University of Inner Mongolia Autonomous Region, Hohhot 010022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Ling","family":"Du","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Inner Mongolia Normal University, Hohhot 010022, China"},{"name":"Key Laboratory of Biodiversity Conservation and Sustainable Utilization in Mongolian Plateau for College and University of Inner Mongolia Autonomous Region, Hohhot 010022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"given":"Wenjing","family":"Mu","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Inner Mongolia Normal University, Hohhot 010022, China"},{"name":"Key Laboratory of Biodiversity Conservation and Sustainable Utilization in Mongolian Plateau for College and University of Inner Mongolia Autonomous Region, Hohhot 010022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Daxi Biotechnology Co., Ltd., Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Yongming","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Inner Mongolia Normal University, Hohhot 010022, China"},{"name":"Key Laboratory of Biodiversity Conservation and Sustainable Utilization in Mongolian Plateau for College and University of Inner Mongolia Autonomous Region, Hohhot 010022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70000","DOI":"10.1002\/btm2.70000","article-title":"Stem Cell Therapies in the Clinic","volume":"10","author":"Acharya","year":"2025","journal-title":"Bioeng. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.jconrel.2024.02.003","article-title":"Genetically Engineered Macrophages as Living Cell Drug Carriers for Targeted Cancer Therapy","volume":"367","author":"Ning","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fang, C.-Y., Wu, C.-C., Fang, C.-L., Chen, W.-Y., and Chen, C.-L. (2017). Long-Term Growth Comparison Studies of FBS and FBS Alternatives in Six Head and Neck Cell Lines. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178960"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"txag044","DOI":"10.1093\/tas\/txag044","article-title":"Production, Pricing, and Incentives in the Fetal Bovine Serum Market","volume":"10","author":"Jungbluth","year":"2026","journal-title":"Transl. Anim. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wosicka-Fr\u0105ckowiak, H., Poniedzia\u0142ek, K., Wo\u017any, S., Kuprianowicz, M., Nyga, M., Jadach, B., and Milanowski, B. (2024). Collagen and Its Derivatives Serving Biomedical Purposes: A Review. Polymers, 16.","DOI":"10.20944\/preprints202408.1673.v1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105204","DOI":"10.1016\/j.identj.2025.105204","article-title":"Characterization and Biological Performance of Anglerfish Collagen and Bovine Collagen","volume":"75","author":"Song","year":"2025","journal-title":"Int. Dent. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1038\/s41563-025-02241-7","article-title":"Instant Assembly of Collagen for Tissue Engineering and Bioprinting","volume":"24","author":"Gong","year":"2025","journal-title":"Nat. Mater."},{"key":"ref_8","first-page":"129","article-title":"Application of Collagen in Bone Regeneration","volume":"50","author":"Li","year":"2025","journal-title":"J. Orthop. Transl."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133004","DOI":"10.1016\/j.ijbiomac.2024.133004","article-title":"Enriched Characteristics of Poultry Collagen over Other Sources of Collagen and Its Extraction Methods: A Review","volume":"273","author":"Jayaprakash","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1074\/jbc.275.1.35","article-title":"The Collagen-Binding a-Domains of Integrins \u03b11\u03b21 and \u03b12\u03b21Recognize the Same Specific Amino Acid Sequence, GFOGER, in Native (Triple-Helical) Collagens","volume":"275","author":"Knight","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gullberg, D. (2014). Cellular Signaling by Collagen-Binding Integrins. I Domain Integrins, Springer.","DOI":"10.1007\/978-94-017-9153-3"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1136\/ard-2023-224129","article-title":"Ablation of Integrin-Mediated Cell\u2013Collagen Communication Alleviates Fibrosis","volume":"82","author":"Sawant","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1038\/s41467-019-10290-1","article-title":"Absorbable Hemostatic Hydrogels Comprising Composites of Sacrificial Templates and Honeycomb-like Nanofibrous Mats of Chitosan","volume":"10","author":"Leonhardt","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2405335","DOI":"10.1002\/adfm.202405335","article-title":"Fish Collagen Cross-Linking Strategies to Improve Mechanical and Bioactive Capabilities for Tissue Engineering and Regenerative Medicine","volume":"34","author":"Leonard","year":"2024","journal-title":"Adv. Funct. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"126279","DOI":"10.1016\/j.ijbiomac.2023.126279","article-title":"Fabrication and Characterization of 3D Printing Biocompatible Crocin-Loaded Chitosan\/Collagen\/Hydroxyapatite-Based Scaffolds for Bone Tissue Engineering Applications","volume":"252","author":"Jirofti","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s42825-025-00225-6","article-title":"Recent Progress of Collagen-Based Hydrogels for Wound Healing: A Review","volume":"8","author":"Jin","year":"2026","journal-title":"Collagen Leather"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2105152","DOI":"10.1002\/advs.202105152","article-title":"Bioactive Materials Promote Wound Healing through Modulation of Cell Behaviors","volume":"9","author":"Li","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41580-024-00715-1","article-title":"Cellular and Molecular Mechanisms of Skin Wound Healing","volume":"25","author":"Martin","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_19","first-page":"33","article-title":"Beneficial Effects of a Novel Shark-Skin Collagen Dressing for the Promotion of Seawater Immersion Wound Healing","volume":"4","author":"Shen","year":"2017","journal-title":"Mil. Med. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1038\/s41467-019-10004-7","article-title":"A Strongly Adhesive Hemostatic Hydrogel for the Repair of Arterial and Heart Bleeds","volume":"10","author":"Hong","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ijbiomac.2022.09.054","article-title":"Preparation of Methacrylated Hyaluronate\/Methacrylated Collagen Sponges with Rapid Shape Recovery and Orderly Channel for Fast Blood Absorption as Hemostatic Dressing","volume":"222","author":"Yang","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_22","first-page":"2613","article-title":"Polydopamine-Modified Collagen Sponge Scaffold as a Novel Dermal Regeneration Template with Sustained Release of Platelet-Rich Plasma to Accelerate Skin Repair: A One-Step Strategy","volume":"6","author":"Zheng","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"124915","DOI":"10.1016\/j.ijbiomac.2023.124915","article-title":"Progress in Preparation and Properties of Chitosan-Based Hydrogels","volume":"242","author":"Lv","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.4103\/1673-5374.257533","article-title":"Collagen-Chitosan Scaffold Impregnated with Bone Marrow Mesenchymal Stem Cells for Treatment of Traumatic Brain Injury","volume":"14","author":"Yan","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"116159","DOI":"10.1016\/j.carbpol.2020.116159","article-title":"Structure-Properties Relationship of Chitosan\/Collagen Films with Potential for Biomedical Applications","volume":"237","author":"Andonegi","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.polymdegradstab.2019.05.023","article-title":"Controlled Degradable Chitosan\/Collagen Composite Scaffolds for Application in Nerve Tissue Regeneration","volume":"166","author":"Si","year":"2019","journal-title":"Polym. Degrad. Stab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ijbiomac.2017.12.136","article-title":"Development of Various Composition Multicomponent Chitosan\/Fish Collagen\/Glycerin 3D Porous Scaffolds: Effect on Morphology, Mechanical Strength, Biostability and Cytocompatibility","volume":"111","author":"Ullah","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.ijbiomac.2020.06.075","article-title":"Current Methods of Collagen Cross-Linking: Review","volume":"161","author":"Adamiak","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zheng, Y., Li, Y., Ke, C., Gao, X., Liu, Z., and Chen, J. (2024). Comparison of Structural and Physicochemical Characteristics of Skin Collagen from Chum Salmon (Cold-Water Fish) and Nile Tilapia (Warm-Water Fish). Foods, 13.","DOI":"10.3390\/foods13081213"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"100218","DOI":"10.1016\/j.scp.2020.100218","article-title":"Antibacterial, Mechanical and Physical Properties of Collagen\u2014Chitosan Sponges from Aquatic Source","volume":"15","year":"2020","journal-title":"Sustain. Chem. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"131277","DOI":"10.1016\/j.ijbiomac.2024.131277","article-title":"Enhanced Physiochemical, Antibacterial, and Hemostatic Performance of Collagen-Quaternized Chitosan-Graphene Oxide Sponges for Promoting Infectious Wound Healing","volume":"266","author":"Sun","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"133032","DOI":"10.1016\/j.ijbiomac.2024.133032","article-title":"Collagen\/Curdlan Composite Sponge for Rapid Hemostasis and Skin Wound Healing","volume":"273","author":"Huang","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5460","DOI":"10.1038\/s41467-024-49578-2","article-title":"Superporous Sponge Prepared by Secondary Network Compaction with Enhanced Permeability and Mechanical Properties for Non-Compressible Hemostasis in Pigs","volume":"15","author":"Jiang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"138086","DOI":"10.1016\/j.ijbiomac.2024.138086","article-title":"The Role of Extraction Method to Collagen Substrates in Enzymolysis of Type I Collagenase","volume":"283","author":"Wu","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"113439","DOI":"10.1016\/j.lwt.2022.113439","article-title":"Impact of Extraction Condition on the Yield and Molecular Characteristics of Collagen from Asian Bullfrog (Rana Tigerina) Skin","volume":"162","author":"Indriani","year":"2022","journal-title":"LWT"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"128389","DOI":"10.1016\/j.ijbiomac.2023.128389","article-title":"Utilizing Epoxy Bletilla Striata Polysaccharide Collagen Sponge for Hemostatic Care and Wound Healing","volume":"259","author":"Tang","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"124148","DOI":"10.1016\/j.ijbiomac.2023.124148","article-title":"Engineering Design of Asymmetric Halloysite\/Chitosan\/Collagen Sponge with Hydrophobic Coating for High-Performance Hemostasis Dressing","volume":"237","author":"Lin","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"120184","DOI":"10.1016\/j.carbpol.2022.120184","article-title":"Root-Shaped Antibacterial Alginate Sponges with Enhanced Hemostasis and Osteogenesis for the Prevention of Dry Socket","volume":"299","author":"Wang","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"He, J., Shi, R., and Ji, R. (2023). Effect of Ultrasound Pre-Treatment on Extraction and Characterization of Collagen from Bactrian Camel Skin. Polymers, 15.","DOI":"10.3390\/polym15081943"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, K., Wang, Z., Ru, A., Wang, K., Cui, W., Zhu, C., Zhao, G., and Hao, J. (2025). Comparative Interaction Mechanisms and Solution Behavior of Cowhide Collagen with Xanthan Gum, Gellan Gum, and Chitosan under Variable Environmental Conditions. Foods, 14.","DOI":"10.3390\/foods14234107"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"He, L., Lan, W., Wang, Y., Ahmed, S., and Liu, Y. (2019). Extraction and Characterization of Self-Assembled Collagen Isolated from Grass Carp and Crucian Carp. Foods, 8.","DOI":"10.3390\/foods8090396"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Liu, Y., Jiang, H., Zhang, L., Tan, Y., Luo, Y., and Hong, H. (2022). Diluted Acetic Acid Softened Intermuscular Bones from Silver Carp (Hypophthalmichthys Molitrix) by Dissolving Hydroxyapatite and Collagen. Foods, 11.","DOI":"10.3390\/foods11010001"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"134969","DOI":"10.1016\/j.ijbiomac.2024.134969","article-title":"Adaptability to the Environment of Protease by Secondary Structure Changes and Application to Enzyme-Selective Hydrolysis","volume":"278","author":"Wang","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_44","first-page":"174","article-title":"Protonated-Chitosan Sponge with Procoagulation Activity for Hemostasis in Coagulopathy","volume":"41","author":"Huang","year":"2024","journal-title":"Bioact. Mater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"120904","DOI":"10.1016\/j.carbpol.2023.120904","article-title":"Injectable Chitosan\/Xyloglucan Composite Hydrogel with Mechanical Adaptivity and Endogenous Bioactivity for Skin Repair","volume":"313","author":"Wei","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"120780","DOI":"10.1016\/j.carbpol.2023.120780","article-title":"Chitosan-Based Hemostatic Sponges as New Generation Hemostatic Materials for Uncontrolled Bleeding Emergency: Modification, Composition, and Applications","volume":"311","author":"Liu","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"119868","DOI":"10.1016\/j.carbpol.2022.119868","article-title":"Mussel-Inspired Polysaccharide-Based Sponges for Hemostasis and Bacteria Infected Wound Healing","volume":"295","author":"Sun","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"151898","DOI":"10.1016\/j.ijbiomac.2026.151898","article-title":"Eu3+-Mediated Dual-Crosslinked Collagen-Mimetic Peptide\/Sodium Alginate Hydrogel for 3D-Printed Skin Wound Dressings","volume":"360","author":"Wei","year":"2026","journal-title":"Int. J. Biol. Macromol."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/18\/18\/2198\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:26:29Z","timestamp":1788949589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/18\/18\/2198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":48,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["polym18182198"],"URL":"https:\/\/doi.org\/10.3390\/polym18182198","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]}}}