Tissue‐Engineered Human Nasal Septal Cartilage Using the Alginate‐Recovered‐Chondrocyte Method

Chia, Stanley H.; Schumacher, Barbara L.; Klein, Travis J.; Thonar, Eugene J.‐M.A.; Masuda, Koichi; Sah, Robert L.; Watson, Deborah

doi:10.1097/00005537-200401000-00006

Cited by 66 publications

(61 citation statements)

References 19 publications

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“…This suggests that the initial extracellular matrix scaffold does not require all components of the final basement membrane and that the UB itself might synthesize any necessary supplementary proteins in an isolated system. In addition, two inert ECM molecules, alginate, which has been used extensively in cartilage tissue engineering (42)(43)(44), and Puramatrix, which was successfully used to support neuronal migration (45) and to promote osteoblast differentiation (46), did not support UB branching. This may be due to the inability of the UB to remodel the artificial matrix to allow room for new branches.…”

Section: Discussionmentioning

confidence: 99%

Staged in vitro reconstitution and implantation of engineered rat kidney tissue

Rosines

Sampogna²,

Johkura³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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A major hurdle for current xenogenic-based and other approaches aimed at engineering kidney tissues is reproducing the complex three-dimensional structure of the kidney. Here, a stepwise, in vitro method of engineering rat kidney-like tissue capable of being implanted is described. Based on the fact that the stages of kidney development are separable into in vitro modules, an approach was devised that sequentially induces an epithelial tubule (the Wolffian duct) to undergo in vitro budding, followed by branching of a single isolated bud and its recombination with metanephric mesenchyme. Implantation of the recombined tissue results in apparent early vascularization. Thus, in principle, an unbranched epithelial tubular structure (potentially constructed from cultured cells) can be induced to form kidney tissue such that this in vitro engineered tissue is capable of being implanted in host rats and developing glomeruli with evidence of early vascularization. Optimization studies (of growth factor and matrix) indicate multiple suitable combinations and suggest both a most robust and a minimal system. A whole-genome microarray analysis suggested that recombined tissue recapitulated gene expression changes that occur in vivo during later stages of kidney development, and a functional assay demonstrated that the recombined tissue was capable of transport characteristic of the differentiating nephron. The approach includes several points where tissue can be propagated. The data also show how functional, 3D kidney tissue can assemble by means of interactions of independent modules separable in vitro, potentially facilitating systems-level analyses of kidney development. kidney development ͉ systems biology ͉ tissue engineering

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Section: Discussionmentioning

confidence: 99%

Staged in vitro reconstitution and implantation of engineered rat kidney tissue

Rosines

Sampogna²,

Johkura³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Cell-associated glycosaminoglycan (GAG) accumulation during 3D culture over 2 weeks was chosen as a marker of chondrogenesis during part I. GAG was chosen over collagen and other matrix components because of ease of measurement for the high-throughput assay and because GAG accumulates in greater quantity than collagen during early culture in alginate. 5,10,11 The cell-associated portion of GAG was assessed because of its usefulness for creation of scaffold-free ARC constructs.…”

Section: 10mentioning

confidence: 99%

“…1,2 Expanded cells are then cultured in a three-dimensional (3D) scaffold such as alginate, agarose, or polyglycolic acid, inducing redifferentiation and production of ECM. [3][4][5] The capacity of cells to redifferentiate and form cartilaginous tissue becomes impaired with increasing levels of expansion. [2][3][4][5] Variables such as medium composition, growth factors, cell seeding density, 3D scaffold properties, and physical stimulation influence the ability of expanded cells to redifferentiate and produce functional cartilaginous ECM.…”

mentioning

confidence: 99%

Insulin-like Growth Factor-I and Growth Differentiation Factor-5 Promote the Formation of Tissue-Engineered Human Nasal Septal Cartilage

Alexander

Sage²,

Chen

et al. 2010

Tissue Engineering Part C: Methods

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Introduction: Tissue engineering of human nasal septal chondrocytes offers the potential to create large quantities of autologous material for use in reconstructive surgery of the head and neck. Culture with recombinant human growth factors may improve the biochemical and biomechanical properties of engineered tissue. The objectives of this study were to (1) perform a high-throughput screen to assess multiple combinations of growth factors and (2) perform more detailed testing of candidates identified in part I. Methods: In part I, human nasal septal chondrocytes from three donors were expanded in monolayer with pooled human serum (HS). Cells were then embedded in alginate beads for 2 weeks of culture in medium supplemented with 2% or 10% HS and 1 of 90 different growth factor combinations. Combinations of insulin-like growth factor-I (IGF-1), bone morphogenetic protein (BMP)-2, BMP-7, BMP-13, growth differentiation factor-5 (GDF-5), transforming growth factor b (TGFb)-2, insulin, and dexamethasone were evaluated. Glycosaminoglycan (GAG) accumulation was measured. A combination of IGF-1 and GDF-5 was selected for further testing based on the results of part I. Chondrocytes from four donors underwent expansion followed by threedimensional alginate culture for 2 weeks in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5. Chondrocytes and their associated matrix were then recovered and cultured for 4 weeks in 12 mm transwells in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5 (the same medium used for alginate culture). Biochemical and biomechanical properties of the neocartilage were measured. Results: In part I, GAG accumulation was highest for growth factor combinations including both IGF-1 and GDF-5. In part II, the addition of IGF-1 and GDF-5 to 2% HS resulted in a 12-fold increase in construct thickness compared with 2% HS alone ( p < 0.0001). GAG and type II collagen accumulation was significantly higher with IGF-1 and GDF-5. Confined compression modulus was greatest with 2% HS, IGF-1, and GDF-5. Conclusion: Supplementation of medium with IGF-1 and GDF-5 during creation of neocartilage constructs results in increased accumulation of GAG and type II collagen and improved biomechanical properties compared with constructs created without the growth factors.

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“…Proper mechanical properties are also required. Along with the synthetic scaffolds, many naturally derived scaffolds have been developed and examined in vitro and/or in vivo, including hyaluronate (HA), [9][10][11] fibrin, 12-14 collagen, 15 alginate, 16,17 and chitosan. 18 Although these materials have met those criteria in vitro, hyaline cartilage tissue formation still remains challenging.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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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.

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Tissue‐Engineered Human Nasal Septal Cartilage Using the Alginate‐Recovered‐Chondrocyte Method

Cited by 66 publications

References 19 publications

Staged in vitro reconstitution and implantation of engineered rat kidney tissue

Staged in vitro reconstitution and implantation of engineered rat kidney tissue

Insulin-like Growth Factor-I and Growth Differentiation Factor-5 Promote the Formation of Tissue-Engineered Human Nasal Septal Cartilage

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

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