There is a need for new methods to promote recovery from organ failure and regenerative medicine is an option that should be considered. Tissue engineering by decellularization and 3d bioprinting. A successful regenerative medicine strategy for wholeorgan replacement would represent a. Tissue engineering is the study of the growth of new connective tissues, or organs, from cells and a collagenous scaffold to produce a fully functional organ for implantation. The end of the beginning for tissue engineering the lancet. The results of the present study not only confirm the concept of whole organ decellularization, as previously shown 5, 19 21, 24, 27 29, but also provides methodology of organ engineering in a large sizescale adapted from previous rodent studies that will be important for clinical translation of this regenerative medicine approach for. Decellularization of tissues and even whole organs. An effective alternative to traditional organ transplantation is needed in order to increase the number of organs available for transplantation, decrease patient waitlist times, and improve longterm outcomes. It applies the principles of engineering and life sciences toward a biological substitutes that restore, maintain, or improve tissue function or a whole organ. Perfusion decellularization of whole organs nature protocols.
Development of perfusion bioreactor for whole organ. Scaffolds that most closely match the criteria for an ideal scaffold and most closely mimic the structure of trabecular bone are made by foaming. Tissue engineering may be regarded as the backbone of reconstructive surgery. In an effort to address this need, research focused on whole organ tissue engineering has flourished over the last 5 years.
The approach is elegant but fraught with challenges and opportunities for improvement. Efforts are now being undertaken for engineering a variety of tissue and organ types with an emphasis on the application of stem cells. Whole organ tissue engineering is a potential breakthrough in vascularized tissue engineering, with an ability to leapfrog the current approaches with synthetic biomaterials and their associated. Herein, we present techniques for tissue clearing in which whole organs and bodies are rendered macromoleculepermeable and optically transparent, thereby exposing their. Optimized protocol for whole organ decellularization. Alternative strategies have been developed, including implantation of 3d constructs and tissuewholeorgan engineering. The study was performed in rat kidneys which were decellularized by a sdsbased perfusion protocol. The key difference between tissue engineering and regenerative medicine is that tissue engineering is defined as a practice of combining scaffolds, cells, and biologically active molecules into functional tissues while regenerative medicine is a broad field which includes tissue engineering and selfhealing with the help of foreign biological. The organ reengineering group at the center for engineering in medicine is working to develop new applications to increase the viability of transplantable organs. Our group was the first to establish the whole liver engineering approach to create grafts that are transplantable and may potentially serve as alternatives to donor livers.
Efforts to provide an alternative source have led to the development of organ engineering, a discipline that combines cell biology, tissue engineering, and cellorgan transplantation. Comparison of methods for wholeorgan decellularization in. The idea of tissue decellularization to gain matrices for tissue engineering is promising. It is possible to supply almost all surgical implants skin, blood vessels, ligaments, heart valves, joint surfaces, nerves through the developments in tissue engineering. Tissue engineering has emerged at the intersection of numerous disciplines to meet a global clinical need for technologies to promote the regeneration of functional living tissues and organs. Recent breakthroughs in the decellularization of solid organs and repopulation with desired cell populations have generated neoorgan constructs with promising functional outcomes. Perfusiondecellularized pancreas as a natural 3d scaffold for pancreatic tissue and whole organ engineering. A wholeorgan regenerative medicine approach for liver. Tissue engineering toward organspecific regeneration and.
However, use of decellularized whole organs and their applications in. Jones, in biomaterials, artificial organs and tissue engineering, 2005. Tissue engineering has also been defined as understanding the principles of tissue. At present, the clinical applicability of these strategies is inversely proportional to the longterm cellular. Tissue engineering evolved from the field of biomaterials development and refers to the practice of combining scaffolds, cells, and biologically active molecules into functional tissues. A decade of progress in tissue engineering ali khademhosseini. This multidisciplinary journal brings together the principles of engineering and life sciences in the creation of artificial tissues and regenerative medicine. Application of wholeorgan tissue engineering in hepatology ncbi. Application of wholeorgan tissue engineering in hepatology. Wholeorgan tissue engineering is a potential breakthrough in vascularized tissue engineering, with an ability to leapfrog the current approaches with synthetic biomaterials and their associated.
Imagine implant materialsthat can grow, reshapethemselves, or change theirfunction as the body requires professor m. The ultimate goal of these processes is to provide tissue constructs or regenera. This manuscript describes the fundamental concepts of wholeorgan engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffold, techniques for the recellularization process and important aspects regarding bioreactor design to. Wholeorgan engineering with natural extracellular materials architecture is validated in comparison to untreated cadaveric tissue with microscopy to ensure tissue integrity is not compromised 12,17,22,28,32,35. A recent innovation in tissue and organ engineering is the technique of wholeorgan decellularization, which allows the production of complex threedimensional extracellular matrix ecm bioscaffolds of the entire organ with preservation of the intrinsic vascular network. Whole organ engineering has emerged as a promising alternative avenue to fill the gap of donor organ shortage in organ transplantation. There are two schools of thought while dealing with tissue engineering techniques. The goal of tissue engineering is to assemble functional constructs that restore, maintain, or.
Effects of perfusionbased decellularization on vascular integrity. Cellbased therapies and hepatic tissue engineering have been considered as alternatives to liver transplantation, but neither has proven effective to date. Reconstructive surgeries following cancer resection and tissue loss from traumatic injury can require extensive amounts of tissue, often with the patient as the sole source for autologous materials. With the advent of whole organ decellularization, extracellular matrix scaffolds suitable for organ engineering were generated from numerous tissues, including the heart, lung, liver, kidney, and pancreas, for use as alternatives to traditional organ transplantation. An alternative approach is to bioengineer organs to be utilized in vivo, replacing diseased or malfunctioning human organs. The true potential of the field of transplant surgery remains limited due to shortages of available transplantable allografts and, following transplantation, acute and chronic rejection with need for lifelong immune suppression. Decellularization and recellularization of threedimensional matrix scaffolds.
Organ reengineering massachusetts general hospital. Tissue engineering is the preeminent, biomedical journal advancing the field with cuttingedge research and applications that repair or regenerate portions or whole tissues. Whole organ sheep kidney tissue engineering and in vivo. Recent accomplishments in tissue decellularization provide acellular tissuederived scaffolds that retain the naturedesigned structure from the whole organ level. View enhanced pdf access article on wiley online library. Pdf application of wholeorgan tissue engineering in. Novel detergent for whole organ tissue engineering. A commonly applied definition of tissue engineering, as stated by langer and vacanti, is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve biological tissue function or a whole organ. The goal of tissue engineering is to assemble functional constructs that restore, maintain, or improve damaged tissues or whole organs. The therapy of choice for endstage liver disease is wholeorgan liver transplantation, but this option is limited by a shortage of donor organs. Over the last several years, engineered organs have been implanted into rodent recipients and have shown modest function. To refine the decellularization protocol of whole porcine liver, which holds great promise for liver tissue engineering.
Whole organ sheep kidney tissue engineering and in vivo transplantation. Initially hailed as the ultimate solution to organ failure, engineering of vascularized tissues such as the liver has stalled because of the need for. A commonly applied definition of tissue engineering, as stated by langer and vacanti is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve biological tissue function or a. Instead, these materials depend on endogenous recruitment of cells that have the capacity to form sitespecific functional tissue. The aim of the present study is to establish a safe and reproducible protocol for solid tissue decellularization that prevents the architecture of the matrix with the inherent vascular network. The aim of tissue engineering is to develop tissue and organ substitutes for maintaining. Recovery from endstage organ failure presents a challenge for the medical community, considering the limitations of extracorporeal assist devices and the shortage of donors when organ replacement is needed. Imagine a world wheretransplant patients do not waitfor a donor or a world whereburn victims leave the hospitalwithout disfiguring scars. The complexity of many tissues and organs, coupled with confounding factors that may be associated with the injury or disease underlying the need for repair, is a challenge to traditional engineering.
An overview of tissue and whole organ decellularization. In recent years, the field of whole organ engineering has been expanding within the termis community. Tissue engineering and the road to whole organs vacanti. Singlecell phenotyping within transparent intact tissue. Using histological methods, the extent of ecm damage in collagendominated tissue has been quantified by measuring collagen. Optimizing perfusiondecellularization methods of porcine. Difference between tissue engineering and regenerative. Organ transplantation remains the only solution to many diseases, including organ failure.
Whole organ tissue engineering is akin to converting a ford into a ferrari while driving at top speed. Tissue engineering is multidisciplinary by necessity an interdisciplinary field that applies the principles of engineering and life sciences towards the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ langer and vacanti, science 1993 medical doctors biologists chemists engineers. The term liver tissue engineering summarizes one of the ultimate goals of modern biotechnology. Approximately 120,000 patients are currently on the organ waiting list in the u. Ultimately, the goal of tissue engineering is to regenerate tissues and restore organ function through cell implantation and matrix incorporation into the.
Biomedical researchers now face the challenge of adequately and efficiently recellularizing these organ scaffolds. Engineering tissue, however, faces an outstanding knowledge gap in the challenge to fully recapitulate complex organspecific features. Unlike the wholeorgan engineering approaches described previously, but akin to muscle replacement, these extracellular matrix scaffold materials are typically used without addition of a target organ cell population. Red contours indicate manual groundtruth segmentations, and yellow conto. The direct infusion of hepatocytes in humans is an established methodology proposed to treat inborn errors of metabolism but is characterized by shortterm clinical bene.
Tissue engineering has been recognized as a translational approach to replace damaged tissue or whole organs. Tissue engineering aims to regenerate and recapitulate a tissue or organ that has lost its function. Tissue engineering te is a multidisciplinary science aimed at developing biological. The focus of our group is to engineer therapies for liver regenerative medicine. Effects of perfusionbased decellularization on vascular integrity, materials. Whole organ tissue engineering for various organs, including the heart, lung, liver, and kidney, has demonstrated promising results for end. View enhanced pdf access article on wiley online library html view download pdf for offline viewing.