Shape memory polymers (SMPs) represent an innovative class of materials that possess programmed, reversible shape-changing capabilities in response to external stimuli. The recent emergence of SMPs’ advanced manufacturing, specifically 4D printing, has created exceptional opportunities for use in biomedical engineering. This review presents a critical synthesis of the latest advances in the chemistry, biomedical applications, manufacturing strategies, and clinical translation of SMPs, highlighting vat photopolymerization techniques, such as stereolithography (SLA) and digital light processing (DLP). Notably, 4D-printed SMPs can promote spatiotemporally controlled architectures, and applications include minimally invasive implants, dynamic tissue scaffolds, and multifunctional drug delivery. This paper focuses on recent advances in resin design, multi-responsive and nanocomposite resins, AI-guided material discovery, and emerging biocompatible and biodegradable formulations, while outlining current roadblocks to clinical implementation, including cytotoxicity, sterilization, regulatory compliance, and device shelf-life. Our goal is to elucidate the relationship between material design, processing, and biomedical performance to inform researchers of potential future directions for 4D-printed SMPs and next-generation, patient-centered medical devices.

Although covalently crosslinked gelatin hydrogels have been investigated for use in 3D cell culture due to inherent bioactivity and proliferation within the denatured collagen precursor, the stability of the matrix, and relatively inexpensive synthesis, current systems lack precise control over mechanical properties, including homogeneity, stiffness, and efficient diffusion of nutrients to embedded cells. Difficulties in modifying gel matrix composition and functionalization have limited the use of covalently crosslinked gelatin hydrogels as a three-dimensional (3D) cell culture medium, lacking the ability to tailor the microenvironment for specific cell types. In addition, the currently utilized chain-growth photopolymerization mechanism for crosslinking hydrogels has a potential for side reactions between the matrix backbone and components of the cell surface, requires a high concentration of radicals for initiation, and only cures with long irradiation times, which could lead to cytotoxicity. To overcome these limitations, a superfast curing reaction mechanism, in which a thiol monomer reacts efficiently with non-homopolymerizable alkenes, is suggested. This mechanism reliably produces a well-defined matrix that does not require a high radical concentration for photoinitiation. Mechanical customization of the hydrogel is largely achievable through variation in degree of functionalization of the gelatin backbone, dependent on reaction conditions such as pH, allyl concentration, and time. This work provides a mechanistic framework for GelAGE hydrogel fabrication by elucidating the molecular mechanism of gelatin functionalization with AGE and the thiol-ene crosslinking reactions controlling network stiffness. These insights provide the foundation for engineering hydrogels that mimic the viscoelastic and structural characteristics of cartilage, enabling advanced in vitro models for osteoarthritis research.