Chronic wounds, or ulcers, pose a significant challenge to public health, affecting millions annually and imposing substantial financial burdens. Conventional medical approaches often fail to address these wounds effectively, necessitating the exploration of new methods. Regenerative medicine and tissue engineering have emerged as promising avenues to promote tissue regeneration. This review focuses on collagen-based biomaterials as potential therapeutic interventions for chronic skin wounds, particularly infective and diabetic ulcers. The review categorizes different approaches based on their action mechanisms, aiming to optimize therapeutic units and promote more efficient healing. Collagen, a key component of the extracellular matrix (ECM), is biocompatible and biodegradable, making it suitable for tissue engineering and regenerative medicine. However, its rapid degradation rate and animal origin pose limitations. To enhance stability and functionality, collagen can be crosslinked or copolymerized with other biomaterials. Various studies have explored the use of collagen scaffolds in combination with other biopolymers to treat chronic wounds, including diabetic foot ulcers (DFUs). The review highlights the importance of scaffold design in promoting wound healing. Scaffolds can be functionalized with various components to address specific issues such as angiogenesis, inflammation, oxidative stress, and microbial infections. For example, collagen scaffolds can be loaded with growth factors like VEGF to enhance angiogenesis, or with anti-inflammatory agents like thymosin beta 4 to reduce inflammation. Additionally, scaffolds can incorporate antioxidant molecules like N-acetylcysteine to counteract oxidative stress and antimicrobial agents to combat infections. The review also discusses the promotion of cell proliferation and extracellular matrix (ECM) regeneration. Strategies include incorporating growth factors, using natural extracts, and designing scaffolds that mimic the ECM to provide a favorable environment for tissue regeneration. For instance, scaffolds containing doxycycline can modulate the inflammatory response and MMP activity, while those with silver nanoparticles can enhance angiogenesis. Overall, the review provides a comprehensive overview of the use of collagen-based biomaterials in treating chronic wounds, emphasizing their potential in accelerating healing, reducing healthcare costs, and improving patients' quality of life.Chronic wounds, or ulcers, pose a significant challenge to public health, affecting millions annually and imposing substantial financial burdens. Conventional medical approaches often fail to address these wounds effectively, necessitating the exploration of new methods. Regenerative medicine and tissue engineering have emerged as promising avenues to promote tissue regeneration. This review focuses on collagen-based biomaterials as potential therapeutic interventions for chronic skin wounds, particularly infective and diabetic ulcers. The review categorizes different approaches based on their action mechanisms, aiming to optimize therapeutic units and promote more efficient healing. Collagen, a key component of the extracellular matrix (ECM), is biocompatible and biodegradable, making it suitable for tissue engineering and regenerative medicine. However, its rapid degradation rate and animal origin pose limitations. To enhance stability and functionality, collagen can be crosslinked or copolymerized with other biomaterials. Various studies have explored the use of collagen scaffolds in combination with other biopolymers to treat chronic wounds, including diabetic foot ulcers (DFUs). The review highlights the importance of scaffold design in promoting wound healing. Scaffolds can be functionalized with various components to address specific issues such as angiogenesis, inflammation, oxidative stress, and microbial infections. For example, collagen scaffolds can be loaded with growth factors like VEGF to enhance angiogenesis, or with anti-inflammatory agents like thymosin beta 4 to reduce inflammation. Additionally, scaffolds can incorporate antioxidant molecules like N-acetylcysteine to counteract oxidative stress and antimicrobial agents to combat infections. The review also discusses the promotion of cell proliferation and extracellular matrix (ECM) regeneration. Strategies include incorporating growth factors, using natural extracts, and designing scaffolds that mimic the ECM to provide a favorable environment for tissue regeneration. For instance, scaffolds containing doxycycline can modulate the inflammatory response and MMP activity, while those with silver nanoparticles can enhance angiogenesis. Overall, the review provides a comprehensive overview of the use of collagen-based biomaterials in treating chronic wounds, emphasizing their potential in accelerating healing, reducing healthcare costs, and improving patients' quality of life.