Solid Organ Bioprinting: Strategies to Achieve Organ Function

Abstract

The field of tissue engineering has advanced over the last decade, but the largest impact on human health should be achieved with the transition of engineered solid organs to the clinic. The number of patients suffering from solid organ disease continues to increase, with over 100,000 patients on the US national waitlist and approximately 730,000 deaths in the United States resulting from end-stage organ disease annually. While flat, tubular, and hollow non-tubular engineered organs have already been implanted in patients, in vitro formation of a fully functional solid organ at a translatable scale has not yet been achieved. Thus, one major goal is to bioengineer complex, solid organs for transplantation, composed of patient-specific cells. Among the myriad of approaches attempted to engineer solid organs, 3D bioprinting offers unmatched potential. This review highlights the structural complexity which must be engineered at nano-, micro-, and mesostructural scales to enable organ function. We showcase key advances in bioprinting solid organs with complex vascular networks and functioning microstructures, advances in biomaterials science that have enabled this progress, the regulatory hurdles the field has yet to overcome, and cutting edge technologies that bring us closer to the promise of engineered solid organs.

Bioprinting and regeneration of auricular cartilage using a bioactive bioink based on microporous photocrosslinkable acellular cartilage matrix

“…), which can effectively alleviate the aseptic inflammatory reaction problem, have become the research hotspot of tissue engineering scaffolds [ [15] , [16] , [17] ]. Three-dimensional (3D) bioprinting technology, which enables precisely defining the spatial distribution of cells and materials, has significant application advantages in the biomimetic construction of tissues and organs [ [18] , [19] , [20] , [21] , [22] ]. Therefore, the integration of hydrogels and bioprinting technology may be the key breakthrough to address the above problems.…”

3D Tissue and Organ Printing—Hope and Reality

“…[91] A wide perspective on the challenges presented by whole organ bioprinting and future directions for the field can be found in a recent comprehensive review. [92] In the next hypothetical scenario, biology is much less cooperative. Referred to here as the "glass ceiling" scenario, it depicts a situation in which most of the complex engineered cellular constructs will not reach an adequate level of functional resemblance to the native tissue.…”

Bioprinting of Complex Multicellular Organs with Advanced Functionality—Recent Progress and Challenges Ahead

“…Moreover, this is only restricted to an area of ≈200 μm in diameter (average size of a single liver lobule). Therefore, from a reverse engineering standpoint, there is hardly anything more complicated in tissue engineering than recreating the architectural organization of a solid organ, [70] like the liver.…”

“…In the example above, there are at least five different populations of specialized cells that are organized with single cell precision in space, and it is well established that their expected function depends almost exclusively on the presence and interaction of the adjacent cell type, [70] as well as the distance from one cell to the next. [71] Therefore, the challenges associated with reproducing this highly intricate set of cellcell and cell-matrix interactions are many.…”