Soon Mo Choi

Cell sheet engineering has emerged as a scaffold-free biofabrication strategy that preserves intrinsic cell–cell and cell–extracellular matrix interactions, demonstrating significant translational potential in regenerative medicine, including cardiac patches, cartilage and skin reconstruction, and corneal transplantation. Despite these advances, thick or multilayered cell sheets remain constrained by diffusion related hypoxia, accumulation of reactive oxygen species, ECM destabilization, and insufficient mechanical reinforcement, all of which interact to compromise long term structural integrity. Rather than providing a conventional survey of recent developments, this conceptual integration review reframes these limitations as a coupled reaction–diffusion–mechanics problem. We examine how redox imbalance and structural insufficiency form a self-reinforcing failure network in thick scaffold-free constructs and propose a reciprocal dual-axis catalytic framework to address this instability. Nanozymes, through catalase-, peroxidase-, and superoxide dismutase-like catalytic activities, regulate oxidative stress, alleviate hypoxic amplification, and establish a permissive redox microenvironment that sustains cell viability and ECM synthesis. In parallel, immobilized enzyme systems facilitate collagen crosslinking and protease modulation, thereby reinforcing ECM architecture and enhancing tensile and shear resilience at the network level. Although nanozyme-based redox regulation and enzyme-mediated structural reinforcement have been extensively explored in oncology, antioxidant therapeutics, and industrial catalysis, their coordinated implications for scaffold-free cell sheet engineering have not been systematically integrated. By articulating a reciprocal dual-axis framework linking redox stabilization with biomechanical maturation, this review provides a systems-level design logic for improving thick cell sheet stability. Finally, we extend this catalytic paradigm beyond regenerative medicine to high-density sheet-like biofabrication systems, including cultured meat and cultured leather, positioning the framework as a transferable engineering principle across emerging biofabrication industries.

Cellulose‐based nanomaterials, particularly cellulose nanofibers (CNF) and cellulose nanocrystals (CNC), have been widely explored as reinforcing agents in polymer composites owing to their high aspect ratio, crystallinity, and abundant surface hydroxyl groups. However, their application in bio‐based leather‐like polymeric materials, which require a unique balance of mechanical robustness, durability, and moisture tolerance, remains insufficiently systematized. This review critically examines the translatability of CNF and CNC reinforcement strategies to sustainable leather substitutes derived from bacterial cellulose (BC), plant fibers, and other bio‐resources, with a focus on addressing key performance limitations such as low mechanical strength, dimensional instability, and poor durability. Particular emphasis is placed on structure–property relationships governed by dispersion behavior, polymer–filler interfacial interactions, and surface modification strategies in moisture‐sensitive and multiphase systems. Unlike existing reviews that primarily address nanocellulose reinforcement in general polymer composites, this work adopts an application‐driven perspective tailored to leather‐like materials. In addition to discussing reinforcement mechanisms, the review considers scalability, multifunctionality, and economic feasibility, while explicitly acknowledging current limitations, including the scarcity of direct studies on leather‐like systems and long‐term durability data. By defining both opportunities and constraints, this review proposes a practical material design framework for the development of next‐generation, high‐performance, and environmentally responsible leather alternatives.

Mechanistic model illustrating the formation of PEDOT-rich domains in CWPU/RCNs/PEDOT:PSS films through solvent evaporation, hydrophobic aggregation, π–π stacking, and hydrogen bonding–driven phase separation during film formation.

Microwave-assited synthesis of CeO ₂ nanoparticles for augmented peroxidase (POD)-like activity.

Cultured meat is emerging as a sustainable alternative to conventional animal agriculture, with scaffolds playing a central role in supporting cellular attachment, growth, and tissue maturation. This review focuses on the development of gel-based hybrid biomaterials that meet the dual requirements of biocompatibility and food safety. We explore recent advances in the use of naturally derived gel-forming polymers such as gelatin, chitosan, cellulose, alginate, and plant-based proteins as the structural backbone for edible scaffolds. Particular attention is given to the integration of food-grade functional additives into hydrogel-based scaffolds. These include nanocellulose, dietary fibers, modified starches, polyphenols, and enzymatic crosslinkers such as transglutaminase, which enhance mechanical stability, rheological properties, and cell-guidance capabilities. Rather than focusing on fabrication methods or individual case studies, this review emphasizes the material-centric design strategies for building scalable, printable, and digestible gel scaffolds suitable for cultured meat production. By systemically evaluating the role of each component in structural reinforcement and biological interaction, this work provides a comprehensive frame work for designing next-generation edible scaffold systems. Nonetheless, the field continues to face challenges, including structural optimization, regulatory validation, and scale-up, which are critical for future implementation. Ultimately, hybrid gel-based scaffolds are positioned as a foundational technology for advancing the functionality, manufacturability, and consumer readiness of cultured meat products, distinguishing this work from previous reviews. Unlike previous reviews that have focused primarily on fabrication techniques or tissue engineering applications, this review provides a uniquely food-centric perspective by systematically evaluating the compositional design of hybrid hydrogel-based scaffolds with edibility, scalability, and consumer acceptance in mind. Through a comparative analysis of food-safe additives and naturally derived biopolymers, this review establishes a framework that bridges biomaterials science and food engineering to advance the practical realization of cultured meat products.

Recently, increased global awareness of environmental sustainability and ethical consumerism has amplified the demand for sustainable alternatives to animal-derived leather. Traditional leather manufacturing faces significant ethical and ecological challenges, including greenhouse gas emissions, excessive water consumption, deforestation, and toxic chemical usage. Vegan leather has emerged as a promising solution, predominantly fabricated from petroleum-based synthetic materials such as polyurethane (PU) and polyvinyl chloride (PVC). However, these materials have sustainability limitations due to their non-biodegradability and associated environmental burdens. To overcome these issues, this review critically explores the feasibility of developing vegan leather using gel-based materials derived from natural and synthetic polymers. These materials offer precise structural controllability, excellent biodegradability, and the potential for significantly improved mechanical performance through hybridization and nanocomposite strategies. Despite their promising attributes, gel-based materials face significant limitations, including insufficient tensile strength, poor abrasion resistance, susceptibility to swelling, limited long-term stability, and challenges in scaling up for industrial production. This paper outlines the structural and physical properties required for viable leather substitutes, reviews opportunities provided by gel-based materials, addresses associated technical challenges, and proposes comprehensive strategies for enhancing mechanical properties and developing sustainable, eco-friendly production processes. Future research directions emphasize hybrid composite development, nanoparticle integration, circular manufacturing processes, and multi-disciplinary collaboration to establish gel-based vegan leather as a viable, sustainable, and market-competitive alternative to conventional animal leather.

Exploiting novel crosslinking chemistry, this study pioneers the use of waterborne polyurethane (WPU) to chemically crosslink porcine-derived gelatin, producing enhanced gelatin hydrogel films through a solvent-casting method. Our innovative approach harnesses the reactive isocyanate groups of WPU, coupling them effectively with gelatin’s hydroxyl and primary amino groups to form robust urea and urethane linkages within the hydrogel matrix. This method not only preserves the intrinsic elasticity of polyurethane but also significantly augments the films’ tensile strength and strain. Comprehensive characterizations of these hydrogel films and pre-formed hydrogel reaction mixtures were conducted using viscosity measurements, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and the universal testing machine (UTM) for tensile-recovery assessments, alongside evaluations of their biocompatibility. The results demonstrated a reduction in pore size with an increase in WPU concentration from 2 to 6% in the developed hydrogels with a decrease in the equilibrium swelling ratio from 15% to 9%, respectively. Further, hydrogels with 6% WPU exhibited the highest tensile stress in both a dry and wet state. The gelatin hydrogel formed with 6% WPU blend also demonstrated the growth and proliferation of CCD-986K (fibroblast) and CCD-1102 (keratinocyte) cells for up to 5 days of co-culturing. The results indicate a notable enhancement in the mechanical properties and biocompatibility of gelatin hydrogels upon the introduction of WPU, positioning these films as superior candidates for biomedical applications such as tissue engineering and wound dressing.