Whole Organ Engineering: Approaches, Challenges, and Future Directions

Abstract

End-stage organ failure remains a leading cause of morbidity and mortality across the globe. The only curative treatment option currently available for patients diagnosed with end-stage organ failure is organ transplantation. However, due to a critical shortage of organs, only a fraction of these patients are able to receive a viable organ transplantation. Those patients fortunate enough to receive a transplant must then be subjected to a lifelong regimen of immunosuppressant drugs. The concept of whole organ engineering offers a promising alternative to organ transplantation that overcomes these limitations. Organ engineering is a discipline that merges developmental biology, anatomy, physiology, and cellular interactions with enabling technologies such as advanced biomaterials and biofabrication to create bioartificial organs that recapitulate native organs in vivo. There have been numerous developments in bioengineering of whole organs over the past two decades. Key technological advancements include (1) methods of whole organ decellularization and recellularization, (2) three-dimensional bioprinting, (3) advanced stem cell technologies, and (4) the ability to genetically modify tissues and cells. These advancements give hope that organ engineering will become a commercial reality in the next decade. In this review article, we describe the foundational principles of whole organ engineering, discuss key technological advances, and provide an overview of current limitations and future directions.

Supramolecular Biopolymers for Tissue Engineering

“…These figures have been reproduced with permission from the American Chemical Society [117]. 10 Advances in Polymer Technology process is finalized. Low concentrations (<0.5%) of COS showed prolonged viability of human umbilical cord mesenchymal stem cells and potential wound healing capabilities with no inflammation response and maturation of granulation tissue.…”

“…However, TE is now reaching a new level of complexity: two-dimensional cell monolayers are moving to three-dimensional constructs (or even to four-dimensional ones) [131][132][133]. Cell lines are being replaced by pluripotent and patient-derived cells [134][135][136], and tissue grafts are evolving to organoids and whole organs [10,16,47,[136][137][138][139][140][141]. As such, the materials employed must improve accordingly.…”

“…It could allow the advancement of patient-specific personalized therapies, sophisticated tissue generation, miniaturization of functional organs, accelerated therapeutic evaluation, and even reduced animal use [9]. Currently, the state-of-the-art of TE is switching from simple in vitro replicas of tissue sections to structurally and biologically complex models of whole organs [10][11][12]. Researchers are also developing dynamic and cell-free scaffolds for regeneration [13][14][15], patient-derived organ models [16], and more elegant molecular delivery systems [17,18].…”

Employing Extracellular Matrix-Based Tissue Engineering Strategies for Age-Dependent Tissue Degenerations

“…In fact, the surrounding environment is important, and 3D cell deposition is necessitated. Tissue engineering technology enables the fabrication of various types of engineered organs such as the pancreas, liver, kidney, ovary, bladder, cornea, muscle, skin, vessel, esophagus, and the like using SCs and biomaterials (Figure 2) [127][128][129][130][131][132][133][134][135][136][137]. Although numerous hurdles (i.e., low cell survival, immune response, and insufficient functions) remain to be overcome, many studies have revealed the effectiveness of engineered tissue transplantation as a novel regeneration method [138,139].…”

“…Although numerous hurdles (i.e., low cell survival, immune response, and insufficient functions) remain to be overcome, many studies have revealed the effectiveness of engineered tissue transplantation as a novel regeneration method [138,139]. Some simple tissues (i.e., artificial epidermis) that are relatively easier to engineer, as well as some vital organs that are in high demand for transplantation, have been developed and are progressing favorably [66,127]. Furthermore, to achieve highly precise engineered tissues, novel biofabrication methods such as 3D bioprinting are being developed actively [140][141][142].…”