Hannah Agten

Hydrogels are widely used in cartilage tissue engineering but fail to replicate key mechanical features of native cartilage, particularly its near-zero Poisson’s ratio, which governs lateral deformation under load. Here, we demonstrate that matching deformation behavior in addition to compressive stiffness may contribute to the enhanced chondrogenic response under physiological mechanical stimulation. Human articular chondrocytes were encapsulated in GelMA hydrogels reinforced with melt electrowritten scaffolds engineered to independently tune the effective compressive modulus and Poisson’s ratio. Reinforcement increased the compressive modulus from 33 kPa (neat GelMA) to 245–345 kPa, while reducing the Poisson’s ratio from 0.42 to 0.12 in hybrid designs, approaching native cartilage values. Under dynamic loading, constructs matching both properties showed significantly higher expression of the chondrogenic markers SOX9 and ACAN compared to both neat GelMA and lattice-reinforced constructs, which exhibited a physiologically relevant compressive modulus but a higher Poisson's ratio, along with increased COL2A1 expression compared to the latter specifically. Histological analysis confirmed enhanced and more homogeneous extracellular matrix deposition, with up to 76% GAG and 36% collagen type II coverage. These findings suggest that lateral deformation behavior, alongside compressive stiffness, contributes to directing chondrocyte matrix synthesis under mechanical stimulation, establishing Poisson's ratio as an important and previously underexplored design parameter in cartilage tissue engineering, and providing a framework for engineering mechanically instructive biomaterials for load-bearing tissues.

Despite decades of advancements in melt electrowriting (MEW) and electrospinning (ES), poly( ϵ -caprolactone) (PCL) remains the gold standard polymer for these techniques. Its widespread use is attributed to its processability in both melt and solution, thermal stability, and low melting temperature. MEW and ES enable the fabrication of micro- and nanofibrous scaffolds that can mimic the extracellular matrix of specific tissues. This makes them especially attractive for biomedical applications. However, PCL lacks key properties, e.g., elasticity and suitable biodegradation time, for soft tissue applications. We report for the first time the successful introduction of α -amino acid-based poly(ester amide)s (AAA-PEAs) for MEW processing. Additionally, ES outcomes have been improved compared to existing literature. These polymers were synthesized via polycondensation containing ester and amide functionalities, yielding high molar masses (>40 kg mol ⁻¹ ). L-alanine and L-phenylalanine were selected as α -amino acids, differing in hydrophobic side groups (methyl vs benzyl), resulting in distinct material properties. Both AAA-PEAs showed excellent ES processability, producing uniform fibers (1–3 μ m) without the need of adding PCL. Notably, only the phenylalanine-based PEA was so far processable by MEW, yielding smooth, uniform fibers (25–30 μ m) with no pulsing, fusing, or surface defects. As proof-of-concept, excellent stacking behavior up to 15 layers was achieved. Scaffolds exhibited enhanced ultimate tensile strength (13.70 ± 1.60 MPa) and accelerated biodegradation (72%–77% remaining mass after 16 weeks in phosphate buffered saline at 37 °C) compared to PCL. In vitro studies with MC3T3-E1 cells confirmed cytocompatibility. The above findings underscore the potential of AAA-PEAs as promising biomaterials for soft tissue biomedical applications.

Cartilage tissue engineering aims to restore damaged cartilage using biomaterials, cells, and/or biological cues to support cell growth and tissue repair. Although in the past decades scientific advances have moved the field forward, their translation to a clinical setting is still hampered. One major hurdle to take is to reduce process variability to ensure a predictable biological outcome. Using enabling technologies such as bioprinting has shown the potential to improve process robustness. However, developing bioinks that balance printability with biological functionality remains a major challenge. This study presents the development and structure–property relationships of a novel gelatin-based hydrogel blend, GelMA/GelMA-AEMA, optimized for extrusion-based bioprinting (EBB) while maintaining the crucial biological properties of GelMA for tissue engineering applications. The novel GelMA/GelMA-AEMA blend demonstrated superior flowability and printability compared to GelMA, effectively addressing common 3D-printing defects such as filament shape inhomogeneity. A systematic rheological characterization revealed that the blend exhibits a softer, elastically dominated structure with improved compliance. The blend behaves as a yield-stress fluid with a strong shear-thinning degree, making it highly suitable for EBB. The superior flow properties of the blend are deemed to enhance bond slippage and stress-induced orientation of its more imperfect gel structure, resulting in greater macroscopic deformation and enhanced print fidelity. In addition, histological assessment of a 21-day in vitro study with iPSC-derived chondrocytes suggested that the blend is at least equally performant as GelMA in supporting matrix formation. Histological analysis shows similar matrix deposition profiles, whereas gene expression analysis and compression tests even have suggested superior characteristics for cartilage TE. This study emphasizes the central role of rheology in bioink development and provides foundations for future material development for EBB, with potential implications for cartilage tissue engineering.

Cell‐based regenerative constructs provide hope for the restoration of tissue function in compromised biological conditions such as complex bone defects. A strategy mimicking the cascade of events of postnatal fracture healing suggests an implant design where progenitor cells provide the driving force for the construct's tissue forming capacity, while framing biomaterials provide cells with 3D cues to direct cellular processes. Large bone defects mainly heal through the formation of an intermediate endochondral fracture callus. The authors aimed to develop an in vitro engineered fracture callus manufactured by bioprinting to provide a spatially organized tissue construct based on: i) in vitro 3D primed human periosteum derived cells and ii) biocompatible thiol‐ene alginate hydrogels, mimicking the cells and extracellular matrix present in the different zones of the callus. Cell viability and maintained osteochondrogenic differentiation upon bioprinting is confirmed in vitro. In vivo assessment displays that the developed biomaterials provided essential 3D cues that further guided the cells in their tissue forming process in the absence of additional stimulatory molecules. The reported findings confirm the appeal of a biomimetic approach to steer tissue development of in vitro engineered constructs and illustrate the suitability of bioprinting methodologies for the fabrication of living regenerative implants.