Heqi Xu

Conventional extrusion‐based bioprinting of hydrogels often yields constructs with insufficient mechanical strength. To address this limitation, this study proposes a novel strategy termed Twist‐Assisted Bioprinting (TAB). By employing a custom‐designed twisting module to impose controllable rotation during continuous extrusion, TAB achieves a micro‐helical topological reconstruction of the deposited hydrogel filaments. Experimental results demonstrate that, compared to conventional direct ink writing (DIW), constructs fabricated via TAB exhibit a 9.4% increase in elongation at break and a 24.2% increase in maximum load, alongside a 33.1% reduction in elastic modulus. This shift signifies a mechanical reconfiguration characterized by low modulus and high extensibility. Furthermore, the study elucidates the non‐monotonic influence of printing height, printing speed, rotation speed, and needle spacing on tensile properties, which typically manifest as an initial increase followed by a decline. As a proof of concept, the successful fabrication of a biomimetic tendon featuring distinct helical textures validates the feasibility of TAB and demonstrates its potential for constructing soft tissue scaffolds requiring high extensibility.

Skin, as the outermost layer of human body, serves as barrier for avoiding external risks. However, skin may easily get injured due to traumatic damage and other diseases. Due to the shortage of donor sites, conventional tissue engineering approaches have been broadly utilized for the formation of tissue-engineered skins. Meanwhile, artificial skin models could also be utilized as testing platform for pre-clinical studies. However, conventional tissue engineering methods are struggling with the precise control of cell number and allocation, thereby restricting the level of vascularization and failing to fully recapitulate the complexity of native skins. More recently, three dimensional (3D) bioprinting, on the basis of the advancements of additive manufacturing strategies, have recently appeared as a promising solution to simulate the anatomy and physiology of native skins, thereby providing an alternative fabrication method for vascularized skin models. However, despite technological advances and biomaterial innovations, current 3D bioprinting strategies and biomaterial choices are facing the limitations in hierarchical vascular network recapitulation and microenvironment inadequacy for cellular activities. Therefore, this review systematically summarizes the biomaterial systems from natural, synthetic, and composite aspects combined with typical 3D bioprinting strategies from the basic building element, followed with the applications of 3D bioprinted vascularized tissue constructs as in vitro skin models and in vivo skin grafts. Although there has been tremendous progress in the reconstruction of vascularized skin models, there remains a substantial gap in the functionality between the currently formed skin models and native skin due to material limitations, technical hurdles, and the structural and biological complexity of native skin. Herein, future outlook for the reconstruction of vascularized skin models is discussed and summarized from materials innovations, technical improvements, and AI incorporation.

During 3D bioprinting, when the gravitational force exceeds the buoyant force, cell sedimentation will be induced, resulting in local cell concentration change and cell aggregation which affect the printing performance. This paper aims at studying and quantifying cell aggregation and its effects on the droplet formation process during inkjet-based bioprinting and cell distribution after inkjet-based bioprinting. The major conclusions of this study are as follows: (1) Cell aggregation is a significant challenge during inkjet-based bioprinting by observing the percentage of individual cells after different printing times. In addition, as polymer concentration increases, the cell aggregation is suppressed. (2) As printing time and cell aggregation increase, the ligament length and droplet velocity generally decrease first and then increase due to the initial increase and subsequent decrease of the viscous effect. (3) As the printing time increases, both the maximum number of cells within one microsphere and the mean cell number have a significant increase, especially for low polymer concentrations such as 0.5% (w/v). In addition, the increased rate is the highest using the lowest polymer concentration of 0.5% (w/v) because of its highest cell sedimentation velocity.

3D bioprinting has the capability to create 3D cellular constructs with the desired shape using a layer-by-layer approach. Inkjet 3D bioprinting, as a key

3D bioprinting has the capability to create 3D cellular constructs with the desired shape using a layer-by-layer approach. Inkjet 3D bioprinting, as a key

Three-dimensional (3D) bioprinting precisely deposits picolitre bioink to fabricate functional tissues and organs in a layer-by-layer manner. The bioink used for 3D bioprinting incorporates living cells. During printing, cells suspended in the bioink sediment to form cell aggregates through cell-cell interaction. The formation of cell aggregates due to cell sedimentation have been widely recognized as a significant challenge to affect the printing reliability and quality. This study has incorporated the active circulation into the bioink reservoir to mitigate cell sedimentation and aggregation. Force and velocity analysis were performed, and a circulation model has been proposed based on iteration algorithm with the time step for each divided region. It has been found that (a) the comparison of the cell sedimentation and aggregation with and without the active bioink circulation has demonstrated high effectiveness of active circulation to mitigate cell sedimentation and aggregation for the bioink with both a low cell concentration of 1 × 10 ⁶ cells ml ⁻¹ and a high cell concentration of 5 × 10 ⁶ cells ml ⁻¹ ; and (b) the effect of circulation flow rate on cell sedimentation and aggregation has been investigated, showing that large flow rate results in slow increments in effectiveness. Besides, the predicted mitigation effectiveness percentages on cell sedimentation by the circulation model generally agrees well with the experimental results. In addition, the cell viability assessment at the recommended maximum flow rate of 0.5 ml min ⁻¹ has demonstrated negligible cell damage due to the circulation. The proposed active circulation approach is an effective and efficient approach with superior performance in mitigating cell sedimentation and aggregation, and the resulting knowledge is easily applicable to other 3D bioprinting techniques significantly improving printing reliability and quality in 3D bioprinting.

Recently, 3D bioprinting techniques have been broadly recognized as a promising tool to fabricate functional tissues and organs. The bioink used for 3D bioprinting consists of biological materials and cells. Because of the dominant gravitational force, the suspended cells in the bioink sediment resulting in the accumulation and aggregation of cells. This study primarily focuses on the quantification of cell sedimentation-induced cell aggregation during and after inkjet-based bioprinting. The major conclusions are summarized as follows: (1) as the printing time increases from 0 min to 60 min, the percentage of the cells forming cell aggregates at the bottom of the bioink reservoir increases significantly from 3.6% to 54.5%, indicating a severe cell aggregation challenge in 3D bioprinting, (2) during inkjet-based bioprinting, at the printing time of only 15 min, more than 80% of the cells within the nozzle have formed cell aggregates. Both the individual cells and cell aggregates tend to migrate to the vicinity of the nozzle centerline mainly due to the weak shear-thinning properties of the bioink, and (3) after the bioprinting process, the mean cell number per microsphere increases significantly from 0.38 to 1.05 as printing time increases from 0 min to 15 min. The maximum number of cells encapsulated within one microsphere is ten, and 29.8% of the microspheres with cells encapsulated have contained small or large cell aggregates at the printing time of 15 min.