The Development of a Xenograft-Derived Scaffold for Tendon and Ligament Reconstruction Using a Decellularization and Oxidation Protocol.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, North Carolina, U.S.A.; Molecular Medicine and Translational Science Program, Wake Forest University Graduate School of Arts and Sciences, Winston Salem, North Carolina, U.S.A.
Thorsten M
TM
Seyler
Molecular Medicine and Translational Science Program, Wake Forest University Graduate School of Arts and Sciences, Winston Salem, North Carolina, U.S.A.; Department of Orthopaedic Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina, U.S.A.. Electronic address: dbracey@wakehealth.edu.
Daniel N
DN
Bracey
Department of Orthopaedic Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina, U.S.A.
Johannes F
JF
Plate
Department of Biochemistry, Wake Forest School of Medicine, Winston Salem, North Carolina, U.S.A.
Mark O
MO
Lively
Department of Orthopaedic Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina, U.S.A.
Sandeep
S
Mannava
Department of Orthopaedic Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina, U.S.A.; Virginia Tech-Wake Forest University, School of Biomedical Engineering and Sciences, Blacksburg, Virginia, U.S.A.
Thomas L
TL
Smith
Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, Ohio, U.S.A.
Justin M
JM
Saul
Department of Orthopaedic Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina, U.S.A.
Gary G
GG
Poehling
Virginia Tech-Wake Forest University, School of Biomedical Engineering and Sciences, Blacksburg, Virginia, U.S.A.
Mark E
ME
Van Dyke
Department of Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, U.S.A.
Patrick W
PW
Whitlock
D000818:Animals; D064593:Heterografts / Q000166:cytology*; D008022:Ligaments / Q000166:cytology / Q000637:transplantation; D010084:Oxidation-Reduction; D013552:Swine; D013710:Tendons / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D013718:Tensile Strength; D054457:Tissue Scaffolds; D000519:alpha-Galactosidase / Q000378:metabolism
D000519:alpha-Galactosidase