Are Current Nerve Tissue Processing Methodologies Similar Enough to Use Their Data Interchangeably? An Assessment of the Key Factors Relevant to Regeneration and Functional Outcomes Data
Erick DeVinney, MD1; Anne Engemann, PhD2; Curt Deister, PhD2; Ivica Ducic, MD, PhD1
1Washington Nerve Institute, McLean, VA; 2AxoGen, Alachua, FL
In the past few decades interest in nerve allograft technology has increased greatly. Numerous institutions have developed processing and preservation methodologies in an attempt to create a nerve graft that is safe, physically stable, immunologically tolerated, structurally intact, biologically active and conveniently stored. Unfortunately, achieving this has proven challenging, with only a few reaching commercialization. Nuances in tissue sourcing, processing reagents, processing conditions, quality controls, sterilization methods and storage conditions play a role in the final functionality of each type of nerve allograft. However, general statements are often made on availability, utility and functionality of nerve allografts as a group. To better characterize the similarities and differences between preparation methods, a review of the processes, their characterization assessments and critical factors to success was conducted.
A systematic review of MEDLINE and EMBASE databases was conducted using a comprehensive combination of keywords and a search algorithm according to PRISMA guidelines. Identified candidates were evaluated based on key criteria, categorized and compared to examine key similarities and differences.
Since 1990, 16 institutions have developed and/or patented unique nerve processing methods. Globally, 3 of these methods have been successfully developed to a clinical stage. Processing methodologies were found to vary by tissue source, processing agents, structural preservation, growth factor content, growth inhibitor content, biological activity, mechanical integrity and sterility.
The most prevalent method for reducing the immunologic burden is chemical extraction, with or without detergents. Tissue sources included rat, rabbit, porcine and human. Assessments of cellular extraction, growth factor preservation and growth inhibitor modification/removal were rarely performed, and varied greatly between processes. Preservation of basement membrane structure and laminin assessments were available for many, but not all processes. The degree of structural preservation as well as functional regeneration in both short and long gap models varied greatly by processing methodology. Improved functionality was significantly correlated with a greater degree of structural and laminin preservation as well as enzymatic removal of growth inhibitors. All processing methods demonstrated a favorable safety profile.
Tissue source, processing methodologies, and both structural and bioactive laminin preservation play key roles in the utility of nerve allografts. While safety data and general utility data may be used interchangeably, functional data varied greatly between processing methods and should not be used interchangeably. Given the high degree of variability in the data examined, the tissue source and the processor and/or processing methodology used should be specified to avoid misinterpretation of relevant data.
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