Wanwan Qiu

Bio: Wanwan Qiu is an academic researcher from ETH Zurich. The author has contributed to research in topics: Bone cell & 3D bioprinting. The author has co-authored 1 publications.

Volumetric Tomographic 3D Bioprinting of Heterocellular Bone-like Tissues in Seconds

Abstract: 3D bioprinting has emerged as a powerful tool for custom fabrication of biomimetic hydrogel constructs that support the differentiation of stem cells into functional bone tissues. Existing stem cell-derived in vitro bone models, however, often lack terminally differentiated bone cells named osteocytes which are crucial for bone homeostasis. Here, we report ultrafast volumetric tomographic photofabrication of centimeter-scale heterocellular bone models that enabled successful 3D osteocytic differentiation of human mesenchymal stem cells (hMSCs) within hydrogels after 42 days co-culture with human umbilical vein endothelial cell (HUVECs). It is hypothesized that after 3D bioprinting the paracrine signaling between hMSCs and HUVECs will promote their differentiation into osteocytes while recreating the complex heterocellular bone microenvironment. To this, we formulated a series of bioinks with varying concentrations of gelatin methacryloyl (GelMA) and lithium Phenyl(2,4,6-trimethylbenzoyl)phosphinate (LAP). A bioink comprising 5% GelMA and 0.05% LAP was identified as an optimal material with high cell viability (>90%) and excellent structural fidelity. Increasing LAP concentration led to much lower degree of cell spreading, presumably due to phototoxicity effects. Biochemical assays evidenced significantly increased expression of both osteoblastic markers (collagen-I, ALP, osteocalcin) and osteocytic markers (Podoplanin, PDPN; dentin matrix acidic phosphoprotein 1, Dmp1) after 3D co-cultures for 42 days. Additionally, we demonstrate volumetric 3D bioprinting of perfusable, pre-vascularized bone models where HUVECs self-organized into an endothelium-lined channel within 2 days. Altogether, this work leverages the benefits of volumetric tomographic bioprinting and 3D co-culture, offering a promising platform for scaled biofabrication of 3D bone-like tissues with unprecedented long-term functionality.

Stem Cell-Laden Hydrogel-Based 3D Bioprinting for Bone and Cartilage Tissue Engineering

Abstract: Tremendous advances in tissue engineering and regenerative medicine have revealed the potential of fabricating biomaterials to solve the dilemma of bone and articular defects by promoting osteochondral and cartilage regeneration. Three-dimensional (3D) bioprinting is an innovative fabrication technology to precisely distribute the cell-laden bioink for the construction of artificial tissues, demonstrating great prospect in bone and joint construction areas. With well controllable printability, biocompatibility, biodegradability, and mechanical properties, hydrogels have been emerging as an attractive 3D bioprinting material, which provides a favorable biomimetic microenvironment for cell adhesion, orientation, migration, proliferation, and differentiation. Stem cell-based therapy has been known as a promising approach in regenerative medicine; however, limitations arise from the uncontrollable proliferation, migration, and differentiation of the stem cells and fortunately could be improved after stem cells were encapsulated in the hydrogel. In this review, our focus was centered on the characterization and application of stem cell-laden hydrogel-based 3D bioprinting for bone and cartilage tissue engineering. We not only highlighted the effect of various kinds of hydrogels, stem cells, inorganic particles, and growth factors on chondrogenesis and osteogenesis but also outlined the relationship between biophysical properties like biocompatibility, biodegradability, osteoinductivity, and the regeneration of bone and cartilage. This study was invented to discuss the challenge we have been encountering, the recent progress we have achieved, and the future perspective we have proposed for in this field.

Recent Advances in Macroporous Hydrogels for Cell Behavior and Tissue Engineering

Abstract: Hydrogels have been extensively used as scaffolds in tissue engineering for cell adhesion, proliferation, migration, and differentiation because of their high-water content and biocompatibility similarity to the extracellular matrix. However, submicron or nanosized pore networks within hydrogels severely limit cell survival and tissue regeneration. In recent years, the application of macroporous hydrogels in tissue engineering has received considerable attention. The macroporous structure not only facilitates nutrient transportation and metabolite discharge but also provides more space for cell behavior and tissue formation. Several strategies for creating and functionalizing macroporous hydrogels have been reported. This review began with an overview of the advantages and challenges of macroporous hydrogels in the regulation of cellular behavior. In addition, advanced methods for the preparation of macroporous hydrogels to modulate cellular behavior were discussed. Finally, future research in related fields was discussed.

A Synthetic Dynamic Polyvinyl Alcohol Photoresin for Fast Volumetric Bioprinting of Functional Ultrasoft Hydrogel Constructs

Abstract: Tomographic volumetric bioprinting (VBP) enables fast photofabrication of cell-laden hydrogel constructs in one step, addressing the limitations of conventional layer-by-layer additive manufacturing. However, existing biomaterials that fulfill the physicochemical requirements of VBP are limited to gelatin-based photoresins of high polymer concentrations. The printed microenvironments are predominantly static and stiff, lacking sufficient capacity to support 3D cell growth. We here report a dynamic resin based on thiol-ene photo-clickable polyvinyl alcohol (PVA) and thermo-sensitive sacrificial gelatin for fast VBP of functional ultrasoft cell-laden hydrogel constructs within 7-15 seconds. Using gelatin allows VBP of permissive hydrogels with low PVA contents of 1.5%, providing a stress-relaxing environment for fast cell spreading, 3D osteogenic differentiation of embedded human mesenchymal stem cells and matrix mineralization. Additionally, site-specific immobilization of molecules-of-interest inside a PVA hydrogel is achieved by 4D tomographic thiol-ene photopatterning. This technique may enable spatiotemporal control of cell-material interactions and guided in vitro tissue formation using programmed cell-friendly light. Altogether, this study introduces a synthetic dynamic photoresin enabling fast VBP of functional ultrasoft hydrogel constructs with well-defined physicochemical properties and high efficiency.

Simultaneous fabrication of multiple tablets within seconds using tomographic volumetric 3D printing

Abstract: 3D printing is driving a shift in patient care away from a generalised model and towards personalised treatments. To complement fast-paced clinical environments, 3D printing technologies must provide sufficiently high throughputs for them to be feasibly implemented. Volumetric printing is an emerging 3D printing technology that affords such speeds, being capable of producing entire objects within seconds. In this study, for the first time, rotatory volumetric printing was used to simultaneously produce two torus- or cylinder-shaped paracetamol-loaded Printlets (3D printed tablets). Six resin formulations comprising paracetamol as the model drug, poly(ethylene glycol) diacrylate (PEGDA) 575 or 700 as photoreactive monomers, water and PEG 300 as non-reactive diluents, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as the photoinitiator were investigated. Two printlets were successfully printed in 12 to 32 s and exhibited sustained drug release profiles. These results support the use of rotary volumetric printing for efficient and effective manufacturing of various personalised medicines at the same time. With the speed and precision it affords, rotatory volumetric printing has the potential to become one of the most promising alternative manufacturing technologies in the pharmaceutical industry.