Are synthetic scaffolds suitable for the development of clinical tissue‐engineered tubular organs?

Abstract

Transplantation of tissues and organs is currently the only available treatment for patients with end‐stage diseases. However, its feasibility is limited by the chronic shortage of suitable donors, the need for life‐long immunosuppression, and by socioeconomical and religious concerns. Recently, tissue engineering has garnered interest as a means to generate cell‐seeded three‐dimensional scaffolds that could replace diseased organs without requiring immunosuppression. Using a regenerative approach, scaffolds made by synthetic, nonimmunogenic, and biocompatible materials have been developed and successfully clinically implanted. This strategy, based on a viable and ready‐to‐use bioengineered scaffold, able to promote novel tissue formation, favoring cell adhesion and proliferation, could become a reliable alternative to allotransplatation in the next future. In this article, tissue‐engineered synthetic substitutes for tubular organs (such as trachea, esophagus, bile ducts, and bowel) are reviewed, including a discussion on their morphological and functional properties. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2427–2447, 2014

Functional Reconstruction of Tracheal Defects by Protein-Loaded, Cell-Seeded, Fibrous Constructs in Rabbits

“…8 Approaches utilizing degradable synthetic materials are gaining popularity due to the limited availability, specialized preparation, and storage of donor tissues, and the limited regenerative capacity of non-degradable materials. 9 Our approach is unique in that we harness degradable synthetic materials with a biomimetic architecture. We endeavor to use polymeric scaffolds for trachea repair, utilizing electrospun poly-lactic-co-glycolic acid (PLGA) (on outer surface) and polycaprolactone (PCL) (on inner surface) graded scaffolds reinforced with PCL rings for tracheal defect repair.…”

Engineered Tissue–Stent Biocomposites as Tracheal Replacements

“…The design reported here is, to our knowledge, a unique approach to producing a functional tracheal substitute. We have focused our design on the following key criteria: (1) provide an appropriate biomechanical construct to prevent airway collapse, since this has plagued previous studies of decellularized airway replacement 10,20 ; (2) support rapid vascularization of the implanted scaffold to decrease risk of graft infection and perforation; (3) avoid the use of patient's cells, so that no invasive biopsies or cell culture ''wait time'' is necessary before graft implantation; (4) avoid immunosuppressive treatment by providing an acellular construct; and (5) provide an implant that has mechanical properties similar to native trachea, thereby providing ease of surgical handling. 2 Previous tracheal replacements have focused on decellularization of native airways, 8,9,20,32,33 or on entirely synthetic substrates that are seeded with autologous cells.…”

“…For longer defects, however, some sort of tracheal replacement is often needed. [1][2][3] Numerous approaches have been studied previously, including wholly synthetic materials, 1,3-5 allografts, [4][5][6][7] autografts, 1,6,7 and tissue-engineered decellularized tracheas. 1,4,[8][9][10] All these options have been constrained by problems including tracheal collapse requiring repeated stenting, infection, and erosion into adjacent structures.…”

“…[8][9][10]13,14 Characteristics of an ideal tracheal replacement have been said to include lateral rigidity, longitudinal flexibility, lining of respiratory epithelium, air-tight anastomoses, ability to integrate into adjacent tissue, no requirement for immunosuppressive therapy, and implantability using straightforward surgical techniques. 1,11,12,15 To date, no tracheal replacement has met all of these criteria.…”

“…2,13,14,16 Clinical utilization of allogeneic tracheal transplantation has also been reported, 1,15,17 although this approach requires immunosuppression and surgical flap placement for tissue perfusion, and can lead to airway collapse and a requirement for stenting as well. 2,4,5,16 Clinical application of tissue-engineered, decellularized tracheas was first reported in 2008.…”