TY - JOUR
T1 - The Development of a Xenograft-Derived Scaffold for Tendon and Ligament Reconstruction Using a Decellularization and Oxidation Protocol
AU - Seyler, Thorsten M.
AU - Bracey, Daniel N.
AU - Plate, Johannes F.
AU - Lively, Mark O.
AU - Mannava, Sandeep
AU - Smith, Thomas L.
AU - Saul, Justin M.
AU - Poehling, Gary G.
AU - Van Dyke, Mark E.
AU - Whitlock, Patrick W.
N1 - Publisher Copyright:
© 2016 Arthroscopy Association of North America
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Purpose To evaluate the biological, immunological, and biomechanical properties of a scaffold derived by architectural modification of a fresh-frozen porcine patella tendon using a decellularization protocol that combines physical, chemical, and enzymatic modalities. Methods Porcine patellar tendons were processed using a decellularization and oxidation protocol that combines physical, chemical, and enzymatic modalities. Scaffolds (n = 88) were compared with native tendons (n = 70) using histologic, structural (scanning electron microscopy, porosimetry, and tensile testing), biochemical (mass spectrometry, peracetic acid reduction, DNA quantification, alpha-galactosidase [α-gal] content), as well as in vitro immunologic (cytocompatibility, cytokine induction) and in vivo immunologic nonhuman primate analyses. Results A decrease in cellularity based on histology and a significant decrease in DNA content were observed in the scaffolds compared with the native tendon (P < .001). Porosity and pore size were increased significantly (P < .001). Scaffolds were cytocompatible in vitro. There was no difference between native tendons and scaffolds when comparing ultimate tensile load, stiffness, and elastic modulus. The α-gal xenoantigen level was significantly lower in the decellularized scaffold group compared with fresh-frozen, nondecellularized tissue (P < .001). The in vivo immunological response to implanted scaffolds measured by tumor necrosis factor-α and interleukin-6 levels was significantly (P < .001) reduced compared with untreated controls in vitro. These results were confirmed by an attenuated response to scaffolds in vivo after implantation in a nonhuman primate model. Conclusions Porcine tendon was processed via a method of decellularization and oxidation to produce a scaffold that possessed significantly less inflammatory potential than a native tendon, was biocompatible in vitro, of increased porosity, and with significantly reduced amounts of α-gal epitope while retaining tensile properties. Clinical Relevance Porcine-derived scaffolds may provide a readily available source of material for musculoskeletal reconstruction and repair while eliminating concerns regarding disease transmission and the morbidity of autologous harvest.
AB - Purpose To evaluate the biological, immunological, and biomechanical properties of a scaffold derived by architectural modification of a fresh-frozen porcine patella tendon using a decellularization protocol that combines physical, chemical, and enzymatic modalities. Methods Porcine patellar tendons were processed using a decellularization and oxidation protocol that combines physical, chemical, and enzymatic modalities. Scaffolds (n = 88) were compared with native tendons (n = 70) using histologic, structural (scanning electron microscopy, porosimetry, and tensile testing), biochemical (mass spectrometry, peracetic acid reduction, DNA quantification, alpha-galactosidase [α-gal] content), as well as in vitro immunologic (cytocompatibility, cytokine induction) and in vivo immunologic nonhuman primate analyses. Results A decrease in cellularity based on histology and a significant decrease in DNA content were observed in the scaffolds compared with the native tendon (P < .001). Porosity and pore size were increased significantly (P < .001). Scaffolds were cytocompatible in vitro. There was no difference between native tendons and scaffolds when comparing ultimate tensile load, stiffness, and elastic modulus. The α-gal xenoantigen level was significantly lower in the decellularized scaffold group compared with fresh-frozen, nondecellularized tissue (P < .001). The in vivo immunological response to implanted scaffolds measured by tumor necrosis factor-α and interleukin-6 levels was significantly (P < .001) reduced compared with untreated controls in vitro. These results were confirmed by an attenuated response to scaffolds in vivo after implantation in a nonhuman primate model. Conclusions Porcine tendon was processed via a method of decellularization and oxidation to produce a scaffold that possessed significantly less inflammatory potential than a native tendon, was biocompatible in vitro, of increased porosity, and with significantly reduced amounts of α-gal epitope while retaining tensile properties. Clinical Relevance Porcine-derived scaffolds may provide a readily available source of material for musculoskeletal reconstruction and repair while eliminating concerns regarding disease transmission and the morbidity of autologous harvest.
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U2 - 10.1016/j.arthro.2016.07.016
DO - 10.1016/j.arthro.2016.07.016
M3 - Article
C2 - 27692557
AN - SCOPUS:84999006516
VL - 33
SP - 374
EP - 386
JO - Arthroscopy - Journal of Arthroscopic and Related Surgery
JF - Arthroscopy - Journal of Arthroscopic and Related Surgery
SN - 0749-8063
IS - 2
ER -