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

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• 作者：Thorsten M. Seyler ; M.D. ; Ph.D.^a ; ^b ; Daniel N. Bracey ; M.D.^b ; ^c ; ^{dbracey@wakehealth.edu} ; Johannes F. Plate ; M.D. ; Ph.D.^c ; Mark O. Lively ; Ph.D.^d ; Sandeep Mannava ; M.D. ; Ph.D.^c ; Thomas L. Smith ; Ph.D.^c ; ^e ; Justin M. Saul ; Ph.D.^f ; Gary G. Poehling ; M.D.^c ; Mark E. Van Dyke ; Ph.D.^e ; Patrick W. Whitlock ; M.D. ; Ph.D.^g
• 刊名：Arthroscopy: The Journal of Arthroscopic & Related Surgery
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：33
• 期：2
• 页码：374-386
• 全文大小：2645 K
• 卷排序：33

文摘

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.MethodsPorcine 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.ResultsA 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.ConclusionsPorcine 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 RelevancePorcine-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.