Tissue‐engineered allograft tracheal cartilage using fibrin/hyaluronan composite gel and its in vivo implantation

Abstract

Objectives/Hypothesis: Treatment and management of tracheal defects remain challenging in head and neck surgery. Various reconstruction techniques have been used, with no consensus on the best approach. The purpose of this study was to explore a novel strategy to fabricate tissue-engineered trachea by using fibrin/hyaluronic acid (HA) composite gel and evaluate the feasibility of creating tracheal cartilage.Study Design: A preliminary animal experiment.Methods: Chondrocytes from rabbit cartilage were expanded and seeded into a culture dish at high density to form mechanically stable allograft tracheal cartilage using fibrin/HA composite gel. After a longitudinal cervical skin incision, the trachea was exposed and a rectangular defect (1 Â 0.5 cm) was created on the cervical trachea by scalpel on six rabbits. Tissue-engineered cartilage using fibrin/HA composite was trimmed and fixed to defect boundaries with Tissucol (Baxter International, Deerfield, IL). Postoperatively, the site was evaluated endoscopically, histologically, radiologically, and functionally.Results: Postoperatively, rigid telescopic examination showed that the implanted scaffolds in all cases were completely covered with regenerated mucosa without granulation or stenosis. Histologic data showed ciliated epithelium regenerated at the operated site from 2 months postoperatively. Ciliary beat frequency of ciliated epithelium on implants was very similar to normal respiratory mucosa. Computed tomography images revealed fine luminal contour of the regenerated site. However, allograft cartilage implanted was found to be partially preserved on the postoperative specimen.Conclusions: The tracheal luminal contour and functional epithelial regeneration without graft rejection and inflammation were observed after repair of a tracheal resection using allogeneic implants with chondrocytes cultured with fibrin/HA.

Tracheal reconstruction using chondrocytes seeded on a poly(l-lactic-co-glycolic acid)-fibrin/hyaluronan

“…The mixing ratio of fibrinogen to HA was 10:1 by volume. The suspension of chondrocytes (1.0 × 10 6 cells/mL) was processed as previously described . Then, 250 mL of the fibrin/HA mixture was dropped into an empty Petri dish to form a gel.…”

“…In addition, our group previously reported the feasibility of using allogeneic chondrocytes cultured with fibrin/hyaluronic acid (HA) gel for tracheal reconstruction. However, these approach had limited mechanical strength because of rapid degradation of fibrin/HA in in vivo condition . We hypothesized that combining fibrin/HA gel with PLGA scaffold would generate a system having the requisite mechanical strength and durability, which could overcome the current limitation.…”

The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

“…In one study, a tissue-engineered trachea fabricated from fibrin gel and autologous chondrocytes was transplanted into rabbits; successful regeneration and functional restoration of ciliated epithelial cells on the operated site were achieved without graft rejection and inflammation [90]. Rabbits also have been used to study airway stem cell biology and lineages using purified or enriched specific epithelial cell types to reconstitute denuded tracheal grafts.…”

Translating tissue-engineered tracheal replacement from bench to bedside

“…Naturally derived scaffolds, such as fibrin/hyaluronic acid composites, have been demonstrated to provide tracheal luminal epithelial regeneration and a favorable environment for chondrocytes to maintain their phenotype and synthesize cartilage ECM [50]. However, either polymeric or natural scaffolds may trigger in vivo inflammation reactions, with consequent graft failure to sufficiently support a permanent shape and size in engineered tissue.…”