Abstract <p>Tissue engineering is an interdisciplinary field integrating biology, engineering, and materials science to develop biological solutions for repairing, preserving, or enhancing the function of damaged tissues and organs. Central to this approach are scaffolds, which serve as temporary structural frameworks mimicking the extracellular matrix (ECM) of native tissues. Among these, hydrogel-based scaffolds, particularly those derived from natural polymers such as collagen, chitosan, gelatin, and alginate have garnered significant attention due to their inherent biocompatibility, biodegradability, and ECM-like properties. These natural polymer-based hydrogels form hydrated, porous networks that promote cell adhesion, proliferation, differentiation, and tissue organization while supporting essential nutrient exchange and waste removal. Their biodegradability enables the gradual replacement of the damaged tissue by regeneration. Moreover, the mechanical properties, degradation rates, and bioactivity of hydrogel scaffolds can be fine-tuned through modifications in chemical composition and cross-linking strategies, allowing for application-specific customization in skin, bone, and cartilage regeneration. In this review, we focus on the capability of these scaffolds to deliver growth factors and bioactive compounds which further enhances their therapeutic potential in regenerative medicine, highlighting their pivotal role in advancing tissue engineering solutions.</p> Lay Summary <p>Hydrogel scaffolds made from natural polymers are becoming increasingly popular in tissue engineering due to their biocompatibility and similarity to the extracellular matrix. These polymers, derived from plants and animals, include collagen, gelatin, alginate, and chitosan. They have numerous advantages, including reduced immunological reactions, biodegradability, enhanced cell attachment, mechanical properties, and intrinsic biological functions that promote tissue regeneration. Scientists are looking at different combinations and modifications of these polymers for a variety of uses, including bone and cartilage regeneration, wound healing, and drug delivery. Despite their potential, there are persistent hurdles in reducing degradation rates, increasing mechanical strength, and addressing batch-to-batch discrepancies. These problems continue to drive research efforts toward designing more advanced scaffolds for tissue engineering applications.</p>