Speaker
Description
Introduction
3D tissue printing has advanced significantly and can now create controlled vascular networks in engineered tissues for effective oxygen and nutrient transfer. However, a major challenge with cell-containing bioink hydrogels is their limited printing resolution, which affects the creation of small-scale features like capillaries. Here, we present a novel selective-shrinking-living bioink that facilitates the successful 4D printing of functional human cardiac tissue featuring a hierarchical vascular network that includes small-scale capillaries.
Methods
The fabrication of human vascularized cardiac tissue with selectively shrinking capillaries is achieved through a multi-material 4D bioprinting approach that integrates three distinct living bioinks within a supportive matrix. This strategy enables the construction of functional cardiac tissue embedded with an intrinsic, hierarchical microvascular network. The process involves:
1. Endothelial bioink to define the lumens of the microvasculature
2. Selective-shrinking bioink to induce the rapid contraction of capillary-scale structures
3. Cardiac bioink to form the surrounding myocardial tissue
Following printing, the construct is incubated under physiological conditions, triggering a programmed, time-dependent response in each ink. The endothelial bioink first softens and is gently removed, leaving behind adhered endothelial cells. Next, the selective-shrinking bioink contracts in a controlled manner, forming capillary-like vessels. Ultimately, cellular self-organization completes the maturation of a functional, perfusable cardiac tissue with a hierarchically structured vascular network.
Results and Discussion
As a result of the selective-shrinking-living bioink unique 4D behavior, we have demonstrated the first successful printing of a cell-lined capillary-sized blood vessel. To reach this milestone, we have developed a one-step coordinated multi-kinetic 4D printing technique, in which multiple stimuli-responsive bio-inks are printed and activated according to a kinetically controlled sequence. Proper fabrication was achieved by rationally designing the selective-shrinking-living bioink, and the sequential triggering of the living-bioinks. Additionally, by exploiting the ease with which multiple living-bioinks can be deployed in extrusion-based 3D bioprinting, localization of the novel, shrinking-living bioink was demonstrated, resulting in selective shrinkage and capillary formation only in those specific locations, to create a functional and perfusable human cardiac patch with optimal microvasculature that was well anastomized with the host post transplantation. The use of one-step coordinated multi-kinetic 4D printing combined with the novel selective-shrinking-living bioink constitutes a versatile platform that can be used to advance the field of tissue engineering and regenerative medicine, to allow the generation of small-scale tissue units at their correct size.