In our initial studies, 8 fetal intestinal cells seeded on polymer tubes formed vascularized cysts with a well-differentiated intestinal epithelium lining with mucous secretion. Subsequently, crypt stem cells isolated from adult rats were transplanted onto biodegradable polymer scaffolds to generate stratified epithelium, reminiscent of embryonic gut development; however, the neomucosa was not well differentiated compared with native small intestine. This unit consists of a villous structure with an overlying epithelium and core of stromal cells and preserves the epithelial-mesenchymal interaction thought to be important for normal organ development.
A tube created of nonwoven polyglycolic acid fibers was chosen as the polymer template because the openness of the devices would allow nutrient-waste exchange between implanted cells and surrounding tissue. The organoid units seeded on polymer scaffolds survived, vascularized, proliferated, and formed cystlike structures after implantation. Valvular heart disease is a major cause of morbidity and mortality in the United States. One solution to this problem has been valve replacement.
However, while effective, prosthetic valves have limitations, and no ideal exists for the pediatric population. To overcome these problems, we have been investigating the fabrication of tissue-engineered heart valve leaflets. Some potential advantages of using a tissue-engineered heart valve created from autologous cells include the capacity for normal repair and growth, greater durability provided by a living structure, and biocompatibility of the tissue with minimal risk of infection and thromboembolism.
In previous studies, 9 , 10 component cells of the normal heart valve were harvested and seeded onto a highly porous biodegradable polymer mesh in the shape of a valve leaflet. After in vitro culture, the leaflet was implanted back into the lamb from which the cells were harvested, replacing one of the pulmonary valve leaflets.
These studies 27 , 28 demonstrated appropriate function of the tissue-engineered leaflet, as determined by echocardiography, up to 11 weeks. Future investigations will be directed toward evaluating the long-term durability of the leaflets in vivo and tissue engineering an entire heart valve that can be used for replacement for diseased heart valves.
The fabrication of cartilaginous tissue is one of the most successful areas of tissue engineering. Previous studies 65 - 69 in our laboratory have investigated the fabrication of cartilaginous tissue in the shape of a human ear, a temporomandibular joint disk, nasoseptal implants, meniscal tissue, and tracheal replacement tissue. With the continued critical scarcity of donor organs, tissue engineering offers tremendous potential for alleviating the limitations of current therapy. Various cell types have been transplanted using biodegradable polymer devices, and appropriate tissue structures formed following cell reorganization.
Although there are differences between each tissue, many common elements exist regardless of the cell type. In all cases, implanted cells receive signals to guide their appropriate development from the polymer devices, the surrounding tissue, and the cells themselves. However, tissue engineering of the visceral organs such as liver, small intestine, and kidney is more challenging than tissue engineering of other tissues such as bone, cartilage, bladder, and skin because of their complicated structures and many functions.
Further advances in the area of biomaterials and chemical engineering may provide better polymers that can direct cell growth, maintain differentiated function, and develop higher-ordered tissue structure from originally disorganized cells. Regardless of the tissue type, the cell source and cell expansion may be other important issues in tissue engineering.
The Science of Reconstructive Transplantation | Plastic Surgery Key
For example, the challenge of maintaining in vitro function and survival in hepatocytes makes them the most difficult cell type. It is important to develop the appropriate cell source and culture conditions for the success of tissue-engineered liver. A great effort is under way to isolate and identify the characteristics of stem cell populations for various tissues.
While there are still many important issues to be solved, tissue engineering has been rapidly making progress using a multidisciplinary approach including biology, surgery, and chemical engineering. The success of this approach in animal models will lead to the clinical application of this technology and may ultimately be able to replace lost tissue function.
Reprints: Joseph P. All Rights Reserved. Figure 1. View Large Download. Ann Surg. New York, NY Riss;. Ann Biomed Eng. Cell Transplant. Selective cell transplantation using bioabsorbable artificial polymers as matrices.
J Pediatr Surg. Tissue engineered heart valves. Ann Thorac Surg. Tissue-engineered heart valves. Plast Reconstr Surg.
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Otolaryngol Clin North Am. Survival and function of hepatocytes on a novel three-dimensional synthetic biodegradable polymer scaffold with an intrinsic network of channels. Transplant Proc. Studies of brush border enzymes, basement membrane components, and electrophysiology of tissue-engineered neointestine. Mouse hepatocytes migrate to liver parenchyma and function indefinitely after intrasplenic transplantation.
Permanent engraftment and function of hepatocytes delivered to the liver. Hepatocellular transplantation for metabolic deficiencies. Allogenic and xenogenic hepatocyte transplantation.
The mesentery as a laminated vascular bed for hepatocyte transplantation. Transplantation of isolated hepatocytes into the pancreas. Eur Surg Res. Hepatocellular transplantation into the lung for temporary support of acute liver failure in the rat. Am J Pathol.
Cancer Res. Replacement of liver function in rats by transplantation of microcarrier-attached hepatocytes. New method of hepatocyte transplantation and extracorporeal liver support. Restoration of liver function in Gunn rats without immunosuppression using transplanted microencapsulated hepatocytes.
Artif Organs. Switching from differentiation to growth in heptocytes: control by extracellular matrix. J Cell Physiol. Regenerative signals for heterotopic hepatocyte transplantation.
The Science of Reconstructive Transplantation
Transplantation of hepatocytes using porous, biodegradable sponges. Biodegradable sponges for hepatocyte transplantation. J Biomed Mater Res. Principles of tissue engineering and reconstruction using polymer-cell constructs. Res Soc Symp Proc. Small intestinal submucosa as a small-caliber venous graft. Manuf Rev. J Eng Ind.
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Solid free-form fabrication of drug delivery devices. J Controlled Release. In vitro organogenesis of liver tissue. Ann N Y Acad Sci. Serious renal impairment is associated with long-term parenteral nutrition. Gastroenterol Clin North Am. Am J Gastroenterol. Enterocyte transplantation using cell polymer devices causes intestinal epithelial lined tube formation. Regenerative signals for intestinal epithelial organoid units transplanted on biodegradable polymer scaffolds for tissue engineering of small intestine. Successful anastomosis between tissue-engineered intestine and native small bowel.
Anastomosis between tissue-engineered intestine and native small bowel. End-to-end anastomosis between tissue-engineered intestine and native small bowel. Tissue Eng.
Center for Reconstructive Transplantation
Tissue engineering growth of new cartilage in the shape of a human ear using synthetic polymers seeded with chondrocytes. Temporomandibular joint disc replacement made by tissue-engineered growth of cartilage. Raimund Margreiter, both pioneers in the field of transplantation, have written the foreword for the book. The volume spans such topics as skin rejection, immune monitoring, stem cell-based immunomodulatory strategies, costimulatory blockade, tolerance induction, chronic rejection, ischemia reperfusion injury, nerve regeneration, cortical reintegration, and small and large animal models for reconstructive transplantation.
The book is intended for biomedical researchers and basic scientists in the field of reconstructive transplantation, transplant immunology and regenerative medicine, as well as clinicians, surgeons and multidisciplinary specialists, who are practicing or interested in this novel and exciting field.
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