The global burden of tissue loss or organ damage due to injuries or diseases is immense [1]. Currently, organ transplant treatment procedures are the standard approach to addressing organ damage or loss. However, organ transplantation faces significant limitations, including donor organ shortages, immune rejection, and the risk of complications [2,3]. These challenges highlight the critical need for alternative solutions for tissue regeneration.

It is well known that the body recruits stem cells to repair damaged or injured tissues for recovery and regeneration. However, high levels of inflammation at the injury site, along with the lack of a suitable environment for their growth, often hinder the regeneration process [4]. Therefore, providing a tissue-like environment at the injury site using semi-solid hydrogel-like materials not only absorbs inflammatory exudates but also creates a three-dimensional, tissue-like environment for stem cell growth [5,6]. A recently published report has shown that millions of individuals suffer from conditions that necessitate advanced materials for tissue regeneration [1]. The demand for tissue scaffolds, which provide a framework for cells to grow and regenerate damaged tissues, is projected to reach $5 billion by 2030, growing at a CAGR of 10.1 % annually [7,8].

In conventional two-dimensional (2D) culture systems, cells grow on flat surfaces in only two dimensions, leading to limitations such as genotypic and phenotypic changes [9]. These 2D systems fail to mimic the complex in vivo environment, limiting their relevance in biomedical applications. Environmental conditions, including available nutrients and the physicochemical properties of the matrix, play a crucial role in tissue regeneration and engineering. To address these challenges, three-dimensional (3D) cell growth systems using gel-like structures with tissue-like consistencies have been explored to better mimic in vivo conditions [10,11].

Advancements in 3D bioprinting and microfluidic technologies contribute to the development of engineered tissues by supporting the fabrication and regeneration of tissue structures [12]. Another solution lies in stem cell therapy, where pluripotent stem cells are differentiated into specific cell types needed for the regeneration and repair of tissues [2,4]. Furthermore, Scaffolds and biomaterials that resemble the extracellular matrix (ECM) enable structural support for tissue development and cell proliferation [13]. These approaches collectively represent an important milestone in addressing the limitations of traditional organ transplantation, offering the potential for more effective and sustainable treatments. Among biomaterials, hydrogels are highly suitable for biomedical applications due to their three-dimensional, hydrophilic polymer networks, which can absorb and retain large amounts of biological fluids and water, possess a soft, gel-like consistency, and exhibit biocompatibility that closely mimics the ECM [14,15].

Hydrogels are broadly categorized based on various criteria, reflecting their diverse properties and applications. They can be classified based on their source (natural, synthetic, or hybrid) and ionic charge (cationic, anionic, or non-ionic) [16]. Additionally, they can be categorized by cross-linking method (physical or chemical), stimuli responsiveness (chemical, biochemical, or physical), and polymeric composition (copolymer, homopolymer, or multipolymer) [17,18]. Hydrogels can also be functionalized with ligands to enhance cell adhesion and proliferation characteristics [19]. While only a few hydrogel-based products are currently in clinical use, such as Apligraf® (a living cellular skin substitute containing living cells and ECM proteins to promote wound healing) [20], AlloDerm® (Processed from human allograft skin to create an acellular dermal matrix) [21], and Juvéderm® (a hyaluronic acid-based dermal filler used for facial wrinkles and volume loss) [22], their success highlights the potential of hydrogels in regenerative medicine and wound healing. Hydrogels, functioning as scaffold-like structures, deliver essential biochemical and mechanical cues, especially when integrated with bioreactors, mechanical conditioning, and growth factors [9,12]. Their adjustable mechanical properties and excellent cellular compatibility make hydrogels a highly promising approach in tissue engineering and regenerative medicine, as they effectively promote cell proliferation and differentiation [5,13]. This review highlights the critical role of hydrogel scaffolds and their mechanical properties as fundamental design parameters in tissue engineering. By addressing diverse tissue-specific requirements and exploring the latest advances across various hydrogel classifications and applications, it underscores the potential of tailored hydrogel systems to drive progress in regenerative medicine.