The skin is subject to damage from the surrounding environment. The repair of skin wounds can be very challenging due to several factors such as severe injuries, concomitant infections, or comorbidities such as diabetes. Different drugs and wound dressings have been used to treat skin wounds. Tissue engineering, a novel therapeutic approach, revolutionized the treatment and regeneration of challenging tissue damage. This field includes the use of synthetic and natural biomaterials that support the growth of tissues or organs outside the body. Accordingly, the demand for polymer-based therapeutic strategies for skin tissue defects is significantly increasing. Among the various 3D scaffolds used in tissue engineering, hydrogel scaffolds have gained special significance due to their unique properties such as natural mimicry of the extracellular matrix (ECM), moisture retention, porosity, biocompatibility, biodegradability, and biocompatibility properties. First, this article delineates the process of wound healing and conventional methods of treating wounds. It then presents an examination of the structure and manufacturing methods of hydrogels, followed by an analysis of their crucial characteristics in healing skin wounds and the most recent advancements in using hydrogel dressings for this purpose. Finally, it discusses the potential future advancements in hydrogel materials within the realm of wound healing.

Click chemistry has become a powerful and flexible approach for designing hydrogels used in tissue engineering thanks to its high specificity, fast reaction rates, and compatibility with biological systems. In this review, we introduce the core principles of click chemistry, including efficiency, orthogonality, and modularity, and highlight the main types of reactions commonly used in hydrogel formation, such as azide-alkyne c-cloadditions, thiol-ene/yne reactions, Diels–Alder cycloadditions, and tetrazine–norbornene couplings. These chemistries allow researchers to create covalently crosslinked hydrogels that are injectable, responsive to environmental stimuli, biodegradable, or multifunctional. We also explore strategies to enhance bioactivity, such as incorporating peptides, growth factors, or extracellular matrix components, and enabling precise spatial and temporal control over biological cues. Click-based hydrogels have shown promise across a wide range of tissue engineering applications, from cartilage and skin repair to neural regeneration, corneal healing, and cardiovascular scaffolds, as well as in 3D bioprinting technologies. Despite the many advantages of click chemistry such as mild reaction conditions and customizable material properties, some challenges remain, including concerns around copper toxicity, the cost of specialized reagents, and scalability. Finally, we discuss the status of clinical translation, regulatory considerations, and future directions, including integration with advanced bio fabrication methods, the design of dual-click systems, and the emerging role of in vivo click chemistry in creating next-generation biomaterials.

Drug delivery to the ocular system is affected by anatomical factors like the corneal epithelium, blinking reflex, aqueous blood barrier, and retinal blood barrier, which lead to quick removal from the site and inefficient drug delivery. Developing a drug delivery mechanism that targets specific eye tissue is a major hurdle for researchers. Our study examines the challenges of drug absorption in these pathways. Hydrogels have been researched as a suitable delivery method to overcome some obstacles. These are developed alone or in conjunction with other technologies, such as nanoparticles. Many polymer hydrogel nanoparticle systems utilizing both natural and synthetic polymers have been created and investigated; each has pros and cons. The complex release mechanism of encapsulated agents from hydrogel nanoparticles depends on three key factors: hydrogel matrix swelling, drug-matrix chemical interactions, and drug diffusion. This mechanism exists regardless of the type of polymer. This study provides an overview of the classification of hydrogels, release mechanisms, and the role of controlled release systems in pharmaceutical applications. Additionally, it highlights the integration of nanotechnology in ocular disease therapy, focusing on different types of nanoparticles, including nanosuspensions, nanoemulsions, and pharmaceutical nanoparticles. Finally, the review discusses current commercial formulations for ocular drug delivery and recent advancements in non-invasive techniques. The objective is to present a comprehensive overview of the possibilities for enhancing ocular medication delivery through hydrogel nanoparticle systems.

Hydrogel-based vitreous substitutes have been considered as a potential solution for the treatment of retinal disorders, especially when the natural vitreous body is damaged due to trauma, disease, or surgery. With their high-water content, biocompatibility, and tunable mechanical properties, these hydrogels offer a promising alternative to traditional vitreous substitutes. This review explores the role of polymers and crosslinkers in the development of hydrogel-based substitutes, focusing on how these components contribute to the structure and function of hydrogels. The choice of natural polymers, such as hyaluronic acid and collagen, or synthetic ones, such as polyethylene glycol and polyvinyl alcohol, is crucial to mimic the transparency and flexibility of the vitreous body. Crosslinking methods, including physical, chemical, and enzymatic approaches, help control the gelation process and enhance the mechanical strength of the hydrogel. Furthermore, this review demonstrates how these hydrogels interact with biological tissues, which enhances biocompatibility, cell growth, and tissue repair. This review also discusses the challenges and future directions in improving these hydrogels, particularly in terms of long-term stability, integration with ocular tissues, and appropriate mechanical properties. Overall, hydrogel-based vitreous substitutes have significant potential to improve surgical outcomes and restore vision for patients with vitreous injury.

Tissue engineering is entering a new era, one defined not by passive scaffolds but by smart, adaptive biomaterials that can sense, think, and respond to their surroundings. These next-generation materials go beyond simply providing structure; they interact with cells and tissues in real time. Recent advances in mechanically responsive hydrogels and dynamic crosslinking have demonstrated how materials can adjust their stiffness, repair themselves, and transmit mechanical cues that directly influence cell behavior and tissue growth. Meanwhile, in vivo studies are demonstrating how engineered materials can harness the body’s own mechanical forces to activate natural repair programs without relying on growth factors or additional ligands, paving the way for minimally invasive, force-based therapies. The emergence of electroactive and conductive biomaterials has further expanded these capabilities, enabling two-way electrical communication with excitable tissues such as the heart and nerves, supporting more coordinated and mature tissue growth. Meanwhile, programmable bioinks and advanced bioprinting technologies now allow for precise spatial patterning of multiple materials and living cells. These printed constructs can adapt and regenerate after implantation, combining architectural stability with flexibility to respond to biological changes. This review brings together these cross-cutting advances, dynamic chemical design, mechanobiology-guided engineering, bioelectronic integration, and precision bio-fabrication to provide a comprehensive view of the path forward in this field. We discuss key challenges, including scalability, safety compliance, and real-time sensing validation, alongside emerging opportunities such as in situ stimulation, personalized electromechanical sites, and closed loop “living” implants. Taken together, these adaptive biomaterials represent a transformative step toward information-rich, self-aware scaffolds capable of guiding regeneration in patient-specific pathways, blurring the boundary between living tissue and engineered material.