The continuous advancement of tissue engineering demands the development of novel biomaterials and strategies to create functional and translational tissue constructs. Despite the emergence of new materials, gelatin remains one of the most practical and versatile, widely used biomaterials, combining biocompatibility, tunable properties, and ease of processing, while its biodegradability and derivation from circular economy resources further position it as a sustainable option. This review unfolds the recent trends in gelatin uses across three key areas. First, advances in functionalization, including chemical modifications that enhance mechanical properties and enable smart, self-healing systems, as well as hybridization with natural, synthetic, or inorganic components to expand multifunctionality. Second, innovations in fabrication techniques, from lyophilization and electrospinning to 3D and 4D bioprinting, which allow precise architectural control and patient-specific scaffold design. Third, emerging applications in tissue engineering, demonstrating the latest achievements of gelatin-based hydrogels, nanoparticles, and composites for skin, soft tissue, bone, cartilage, and ocular regeneration, including drug delivery and stimulus-responsive platforms. As predicted in previous reports on gelatin use, this versatile biomaterial continues to be one of the most widely applied and highly valued materials for tissue engineering purposes.

Safe and clinically useful therapeutic drug delivery systems must be developed to fight fatal diseases and disorders like cancer, hypertension, and diabetes, among others. However, these systems face significant development challenges due to their solubility, stability, permeation, cytotoxicity, drug entrapment, and loading issues. Imitations can be avoided by creating innovative drug delivery systems based on nanomaterials, such as nanoclays. As layered nanostructures, nanoclays have many advantageous qualities, such as chemical inertness, colloids (dispersed in blood plasma), a large surface area, and viscosity. Nanoclays are qualified for use as a drug delivery carrier for anti-cancer, antihypertensive, antioxidant, and anti-diabetes medicines based on these qualities. This study discusses the evolution and use of nanoclay in drug delivery research. Clays of various sorts (kaolinite, halloysite, and montmorillonite) have been employed to generate prolonged and targeted drug delivery with enhanced pharmacokinetic characteristics. The modified clay demonstrated optimal drug loading, trapping, release, electrostatic interaction (van der Waals interaction), ion exchange reaction, and immobilization. Finally, nanoclay was employed to create a drug delivery system with enhanced pharmacokinetic properties for proteins, DNA, and pharmaceuticals. Many earlier research investigations have also reported its usage in bio-imaging, tissue engineering, gene transfer, and stem cell separation.

Functional hyaluronic acid/gelatin hydrogel accelerates the closure and healing of diabetic wounds.

Reversing fibroblast-to-myofibroblast transition using surface-engineered nanoparticles to potentially ameliorate fibrotic diseases.

Cellular uptake of anisotropic microparticles in 2D and 3D culture systems.

Eu3+-mediated dual-crosslinked collagen-mimetic peptide/sodium alginate hydrogel for 3D-printed skin wound dressings.

Exploring compartmentalized jet polymerization for novel rod-shaped microgels and their potential in tissue engineering applications.

3D-printable, heat-resistant polycaprolactone-based polymer scaffold for sustained NO release in tissue engineering applications.

Synthetic strategies for the modification of primary hydroxyl and carboxyl groups of Gellan towards the development of advanced biomaterials.

Green synthesis of caffeine-catalyzed citric acid-PPG/PEG crosslinked alginate hydrogel scaffolds for prospective biomedical applications.

Intervertebral disc (IVD) degeneration is a prevalent condition contributing to lower back pain, with limited treatment options that fail to restore full disc function. Tissue engineering shows promise, but most work relies on static culturing methods, which do not mimic the dynamic IVD environment or enable large-scale tissue growth. In this study, we developed an in vitro outer annulus fibrosus (OAF)-cartilage endplate (CEP) interface model and evaluated the effects of perfusion bioreactor culture, with or without cyclic hydrostatic pressure (HP), on tissue integration. Bovine OAF cells were seeded onto electrospun polycarbonate urethane (PCNU) scaffolds and combined with deep zone chondrocytes on 3D membranes. After one week of static culture, constructs were transferred to a perfusion bioreactor (5 mL/min flow) for two weeks, with a subset exposed to dynamic HP (0.1 MPa, 0.5 Hz, 1 hr, 3 times per week). Histological and immunohistochemical analyses confirmed compositional similarity to the native interface, with collagen type I, type II, and aggrecan distributions resembling physiological patterns. Perfusion significantly increased interfacial strength (35.2 ± 14.8 kPa vs 14.8 ± 6.1 kPa static) and DNA content. Although HP reduced DNA content, it did not alter Ki-67 or TUNEL-positive cell percentages. Overall, culturing in a perfusion bioreactor improved the OAF-cartilage integration by increasing tissue growth due to more cellularity, resulting in a stronger interface. These findings demonstrate that perfusion supports development of physiologically relevant IVD constructs and addresses a key translational gap in the field, providing a foundation for scaling engineered tissues to clinically relevant sizes. STATEMENT OF SIGNIFICANCE: Perfusion bioreactors can ameliorate the shortcomings of static culturing methods, and their use could address a translation gap in the field of IVD tissue engineering as they may support the scale-up of tissues to physiological sizes. In this study we demonstrate that OAF and cartilage remain integrated in perfusion culture and it both improves tissue formation and significantly increases the mechanical strength of the interface. Additionally, the application of cyclic HP influences the proliferative state of these tissues without impacting cell viability. This study demonstrates that perfusion culture can be used to bioengineer IVD tissues which may be crucial in facilitating the development of an implant that approximates the features of the native disc.

Developing synthetic materials that replicate the nonlinear and anisotropic mechanical behavior of soft tissues remains a central challenge in tissue engineering. Here, we present a silk fiber-reinforced interpenetrating polymer network (IPN) hydrogel platform engineered to achieve a tunable balance of tensile strength, extensibility, and stiffness. By varying fiber orientation - longitudinal, transverse, and cross-plied (CP) - we introduced directional anisotropy that emulates key structure-function relationships observed in native fibrous tissues. The longitudinal and CP composites exhibited significantly enhanced mechanical performance, with ultimate tensile strengths of 8.1±2.3MPa and 6.8±1.0MPa, and elastic moduli of 28.2±5.4MPa and 25.8±5.3MPa, respectively - significantly larger than the unreinforced hydrogel and transverse configuration. Despite increased stiffness, these configurations maintained physiologically relevant ultimate strains: 46.5±12.0% (longitudinal) to 63.5±33.6% (transverse), closely matching values for native coronary arteries (54.0±25.0%). The CP configuration further reproduced the nonlinear strain-stiffening and pressure-dependent compliance characteristic of coronary adventitia, with measured radial compliance (1.9-2.1 %/100mmHg) within the range of human coronaries and saphenous veins. These findings demonstrate that coupling long-fiber alignment with IPN architecture enables controlled anisotropy and physiological mechanical fidelity, providing a robust framework for next-generation vascular grafts, adventitial wraps, and soft-tissue phantoms.

The use of hydrogel microparticles as granular hydrogels is an emerging approach in tissue engineering, where microparticles offer printability, injectability, and serve as scaffolds for cell culture. While culturing dermal fibroblasts for tissue engineering applications is well reported, there is limited research on culturing primary human pulmonary fibroblasts on granular hydrogels. In this study, we grafted RGD-peptides to alginate, formed microbeads, and investigated the ability of granular hydrogels to support the adhesion and growth of primary normal human dermal fibroblasts (NHDFs) and human pulmonary fibroblasts (HPFa). NHDFs adhered to linear RGD (linRGD)-alginate microbeads and spread on the bead surfaces with increased adhesion with increased peptide concentration (0.3-1.3 mM). In contrast, HPFa did not adhere to the linRGD-alginate microbeads. However, HPFa adhered and spread on flat linRGD-alginate gels, indicating that HPFa do respond to linRGD as an adhesion ligand. Supplementation of Mn2+ resulted in cell adhesion to linRGD-alginate microbeads. Enhanced adhesion and spreading of HPFa to RGD-alginate microbeads were observed when using cyclic RGD. Hence, RGD-alginate microbeads is a promising material for structuring primary human dermal and pulmonary fibroblasts, showing the relevance of using alginate microbeads as scaffolds for 3D cultures with fibroblasts.

Recent advances and strategies for transformation of polydopamine materials from two-dimensional planar to three-dimensional porous for biomedical and catalysis applications.

In situ electrocrosslinkable and immiscible bioadhesive for robust underwater electrophysiological signal interfaces.

Chitosan and γ-polyglutamic acid interfacial polyelectrolyte complexation fibers for tendon biomimicry and regeneration.

Micro- and nanorobots for intelligent bone tissue engineering

Dynamic chitosan-hyaluronic acid hydrogels for extrusion printing: Combined effects of polymer molecular weight and carbon nanofillers.

A critical review on advanced functional bioceramics fabricated by SLA for precision implant applications

Assembly of bioinspired multifunctional microspheres for enhanced alveolar bone regeneration.