Xiaoxiao Han

Poly(L-lactide-co-ε-caprolactone) (PLCL) has emerged as a promising biocompatible copolyester, offering excellent structural flexibility alongside tunable shape-memory properties for advanced biomedical applications. However, its substantial crystallizable amorphous fraction makes it highly susceptible to cold crystallization during powder-bed preheating and laser-induced thermal cycling, resulting in severe powder caking and part warpage during laser powder bed fusion (LPBF). Herein, thermal annealing was used to reduce the crystallizable amorphous fraction available for cold crystallization of PLCL microspheres. Systematic evaluation revealed that annealing at 120 °C for 1 h nearly eliminated the cold-crystallization peak and increased XRD-derived crystallinity of the PLCL microspheres from 34.9% to 47.1%. Meanwhile, the annealed powder retained sufficient elevated-temperature mobility to support stable recoating at a nominal powder-bed preheating temperature of 100 °C, successfully mitigating part warpage during LPBF. At a selected volumetric energy density of 0.37 J/mm³, the printed specimens exhibited an apparent porosity of 11.7 ± 0.4%, a tensile modulus of 206.62 ± 61.39 MPa, and a tensile strength of 5.91 ± 0.72 MPa. The elongation at break reached approximately 180% at 37 °C. As a proof of concept, a PLCL scaffold with a triply periodic minimal surface (TPMS) architecture containing curved and overhanging features was successfully fabricated. These results support thermal annealing as a feasible pretreatment strategy for the LPBF processing of PLCL microspheres and provide a basis for future studies of temperature-responsive PLCL scaffolds.

Light scattering remains a critical barrier in digital light processing (DLP)-based ceramic additive manufacturing, particularly for achieving high precision, fine resolution, and complex geometries. In this study, we present a novel light scattering mitigation strategy by incorporating a multifunctional reactive additive that combines physical light absorption near 405 nm and chemical free radical scavenging. Curcumin effectively suppresses undesired photopolymerization in non-target regions by neutralizing scattered-light-generated radicals, enabling the fabrication of intricate structures with dimensional fidelity approaching the optical resolution limit (∼2.6 pixels). The strategy operates effectively at low concentrations (0.01 wt%) without requiring process parameter tuning, offering a broad process window and high reproducibility. Furthermore, the strategy is generalizable across diverse ceramic systems, including light-colored ceramics (Al ₂ O ₃ , ZrO ₂ , and SiO ₂ ), and dark-colored ceramics (SiC) that are particularly susceptible to scattering. The geometric error of printed SiC components remains below 10% even at high exposure doses of 80 and 100 mJ · cm ⁻² , effectively addressing the long-standing trade-off between curing depth and lateral resolution. This work provides a simple, scalable, and versatile approach for improving resolution in DLP ceramic printing, advancing the reliable production of fine-scale (<50 μm) ceramic architectures for applications in biomedicine, microelectronics, and precision engineering.

Engineering functional soft tissue constructs remains difficult because scaffolds must meet the mechanical, physicochemical, and biological requirements simultaneously. Here, we present a cell-laden hydrogel gyroid scaffold designed to support vascularisation, long-term multicellular culture, and implantation for the development of 3D tissue constructs. The scaffold is structurally optimised to balance nutrient transport and mechanical stability, and is fabricated with high fidelity by mitigating cell-induced light scattering. The gyroid architecture supports the formation of dense microvascular networks throughout the 3D construct, and its curved Gaussian curvature promotes endothelial self-assembly. The scaffold also enables high-density co-culture of HepG2 cells and HUVECs without active perfusion, resulting in a vascularised 3D liver tumour model with enhanced tissue-specific function. Upon subcutaneous implantation in mice, the constructs show enhanced neovascularisation and facilitate tumour formation. These findings identify the gyroid scaffold as a biologically favourable architecture for generating bulk vascularised constructs, with potential applications in disease modelling, drug screening and regenerative medicine.

With the advancement of the personalised medicine industry, multi-material targeted drug delivery systems have garnered significant attention due to the higher drug bioavailability and synergistic effects of combined drug therapies. However, the fabrication throughput of such systems often fails to satisfy the demands of clinical applications. Volumetric printing, distinguished by its remarkable capability for rapid fabrication, presents a promising approach for fabricating these systems. Nevertheless, during volumetric printing, formed parts are prone to displacement relative to their intended locations due to variations in ink density, viscosity, and other factors, resulting in geometric distortion and complicating multi-ink switching. Moreover, functional inks like pH-responsive materials often exhibit high absorbance, resulting in low light penetration and causing printing failures. Consequently, the volumetric printing of multi-material targeted drug delivery systems remains challenging. To address these challenges, this research pre-embedded auxiliary support mechanisms within the forming chamber for precise positioning and fixation of formed components while enabling efficient multi-ink switching. Concurrently, the mathematical mapping relationship between the material absorbance and printing parameters (such as the dimensions of the forming chamber and print parts) was derived based on Lambert-Beer law to guide the optimisation of the process. Leveraging the methodology above, a pH-responsive ink formulation (composed of poly (ethylene glycol) diacrylate, sodium alginate, carboxymethyl chitosan, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate) suitable for volumetric printing and associated processing parameters (25 mW/cm² irradiation intensity, 2% calcium chloride secondary crosslinking for 15 min) were optimised by spectroscopic characterisation of the ink and analysis of swelling behaviour and drug release profiles of printed tablets. Those parameters enabled the rapid fabrication of multi-material, pH-responsive tablets capable of targeted multi-drug release. In conclusion, this study provides an effective approach to addressing critical technical obstacles in multi-material volumetric printing and demonstrates its considerable promise for the advancement of personalized biomedical device fabrication.

Hydroxyapatite/polycaprolactone (HA/PCL) composites have been extensively explored in laser powder bed fusion (L-PBF) for bone tissue engineering. However, conventional mechanical mixing methods for preparing composite powders often yield inhomogeneous compositions and suboptimal flowability. In this study, HA/PCL powders were prepared and optimized for L-PBF using the modified emulsion solvent evaporation method. The morphology, flowability and thermal and rheological properties of the powders were systematically investigated, along with the mechanical and biological properties of the fabricated specimens. The HA/PCL powders exhibited spherical morphologies with a homogeneous distribution of HA within the particles. The addition of small amounts of HA (5 wt% and 10 wt%) enhanced the processability and increased the maximum values of the elastic modulus and yield strength of the specimens from 129.8 MPa to 166.2 MPa and 20.2 MPa to 25.1 MPa, respectively, while also improving their biocompatibility. However, excessive addition resulted in compromised sinterability, thereby affecting both mechanical and biological properties.

Since chondrocytes are highly vulnerable to oxidative stress, an anti-oxidative bioink combined with 3D bioprinting may facilitate its applications in cartilage tissue engineering. We developed an anti-oxidative bioink with methacrylate-modified rutin (RTMA) as an additional bioactive component and glycidyl methacrylate silk fibroin as a biomaterial component. Bioink containing 0% RTMA was used as the control sample. Compared with hydrogel samples produced with the control bioink, solidified anti-oxidative bioinks displayed a similar porous microstructure, which is suitable for cell adhesion and migration, and the transportation of nutrients and wastes. Among photo-cured samples prepared with anti-oxidative bioinks and the control bioink, the sample containing 1 mg/mL of RTMA (RTMA-1) showed good degradation, promising mechanical properties, and the best cytocompatibility, and it was selected for further investigation. Based on the results of 3D bioprinting tests, the RTMA-1 bioink exhibited good printability and high shape fidelity. The results demonstrated that RTMA-1 reduced intracellular oxidative stress in encapsulated chondrocytes under H₂O₂ stimulation, which results from upregulation of COLII and AGG and downregulation of MMP13 and MMP1. By using in vitro and in vivo tests, our data suggest that the RTMA-1 bioink significantly enhanced the regeneration and maturation of cartilage tissue compared to the control bioink, indicating that this anti-oxidative bioink can be used for 3D bioprinting and cartilage tissue engineering applications in the future.

Light-based 3D printing enables the fabrication of biological scaffolds with high precision, versatility and biocompatibility, particularly the cell-laden scaffolds with architecturally complex geometric features. However, many bioprinted tissue scaffolds suffer from low cell viability due to insufficient oxygen and nutrient supply, which is heavily influenced by scaffold structure and cultivation conditions. Current practice relies mainly on resource-intensive trial-and-error methods to optimize scaffolds’ structures and cultivation parameters. In this study, we developed a comprehensive multi-physics model integrating fluid dynamics, oxygen mass transfer, cell oxygen consumption, and cell growth processes to capture cell growth behaviors in scaffolds, establishing a robust theoretical foundation for scaffold structure optimization. The modeling results showed that a large number of parameters, such as system inlet flow rate, geometric feature size, cell parameters, and material properties, significantly impact oxygen concentration and cell growth within the scaffold. A two-step optimization strategy is proposed in this paper and was applied to obtain optimal geometric parameters of channeled scaffolds to demonstrate the model’s effectiveness for scaffold optimization. The model can be employed for scaffolds with arbitrary shapes and various materials, facilitating the optimal design of sophisticated scaffolds for more advanced tissue engineering.

Light-based 3D bioprinting is now employed widely to fabricate geometrically complex constructs for various biomedical applications. However, the inherent light scattering defect creates significant challenges in patterning dilute hydrogels to form high-fidelity structures with fine-scale features. Herein, we introduce a photoinhibiting approach that can effectively suppress the light scattering effect via a mechanism of simultaneous photoabsorption and free-radical reaction. This biocompatible approach significantly improves the printing resolution (~1.2 - ~2.1 pixels depending on swelling) and shape fidelity (geometric error less than 5%), while minimising the costly trial-and-error procedures. The capability in patterning 3D complex constructs using different hydrogels is demonstrated by manufacturing various scaffolds featuring intricate multi-sized channels and thin-walled networks. Importantly, cellularised gyroid scaffolds (HepG2) are fabricated successfully, exhibiting high cell proliferation and functionality. The strategy established in this study promotes the printability and operability of light-based 3D bioprinting systems, allowing numerous new applications for tissue engineering.

The low bioavailability of orally administered drugs as a result of the instability in the gastrointestinal tract environment creates significant challenges to developing site-targeted drug delivery systems. This study proposes a novel hydrogel drug carrier using pH-responsive materials assisted with semi-solid extrusion 3D printing technology, enabling site-targeted drug release and customisation of temporal release profiles. The effects of material parameters on the pH-responsive behaviours of printed tablets were analysed thoroughly by investigating the swelling properties under both artificial gastric and intestinal fluids. It has been shown that high swelling rates at either acidic or alkaline conditions can be achieved by adjusting the mass ratio between sodium alginate and carboxymethyl chitosan, enabling site-targeted release. The drug release experiments reveal that gastric drug release can be achieved with a mass ratio of 1:3, whilst a ratio of 3:1 allows for intestinal release. Furthermore, controlled release is realised by tuning the infill density of the printing process. The method proposed in this study can not only significantly improve the bioavailability of oral drugs, but also offer the potential that each component of a compound drug tablet can be released in a controlled manner at a target location.

Poly-L-lactic acid (PLLA) has gained great popularity with researchers in regenerative medicine owing to its superior biocompatibility and biodegradability, although its inadequate bioactivity inhibits the further use of PLLA in the field of bone regeneration. Zinc oxide (ZnO) has been utilized to improve the biological performance of biopolymers because of its renowned osteogenic activity. However, ZnO nanoparticles tend to agglomerate in the polymer matrix due to high surface energy, which would lead to the burst release of the Zn ion and, thus, cytotoxicity. In this study, to address this problem, carbon–ZnO (C–ZnO) was first synthesized through the carbonization of ZIF-8. Then, C–ZnO was introduced to PLLA powder before it was manufactured as scaffolds (PLLA/C–ZnO) by a selective laser sintering 3D printing technique. The results showed that the PLLA/C–ZnO scaffold was able to continuously release Zn ions in a reasonable range, which can be attributed to the interaction of Zn–N bonding and the shielding action of the PLLA scaffold. The controlled release of Zn ions from the scaffold further facilitated cell adhesion and proliferation and improved the osteogenic differentiation ability at the same time. In addition, C–ZnO endowed the scaffold with favorable photodynamic antibacterial ability, which was manifested by an efficient antibacterial rate of over 95%.