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F3354 Standard Guide for Evaluating Extracellular Matrix Decellularization Processes

2019

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  • Título:
    F3354 Standard Guide for Evaluating Extracellular Matrix Decellularization Processes
  • Descrição: 4.1 Decellularization is used in the preparation of medical products that make use of the native structure and/or composition of the extracellular matrix derived from a specific tissue source. Upon implantation or placement, the decellullarized product is commonly intended to undergo and/or induce constructive remodeling and incorporation into the native host tissue instead of being recognized as foreign material. Typically, immune system recognition of foreign material leads to encapsulation of the material and an aggressive inflammatory response, causing the ultimate rejection or other failure of the product. 4.2 As described above, decellularization is a recognized technique which allows the use of ECM-derived products in medical treatments with a reduced risk of an adverse host immune response and immune rejection by disrupting and removing cells and/or cell contents while aiming to preserve significant features of the ECM structure and/or composition. More complete decellularization is often associated with a beneficial response (1, 2)6 but can also be associated with the loss of important ECM components and the loss of structural or biomechanical integrity from the tissue during the decellularization process (3, 4, 5, 6). Therefore, given the typical objective of producing a product that does not elicit an adverse immune response while maintaining the integrity of the tissue for its intended surgical application, this guide presents a standard approach to the evaluation of decellularization processes, including assessment of adequate decellularization to achieve this end. 4.3 An ideal decellularization process would completely remove source tissue cells and associated cellular content from a tissue or organ, while minimizing unwanted effects on the remaining ECM. However, a more widely encountered and practical representation of an optimized decellularization process exhibits partial removal and/or disruption of resident cells and cellular material to levels within a set of product-specific ranges (acceptance criteria). This guide is intended to aid in evaluating a decellularization process through the mechanisms and extent of decellularization and any potential impacts on the remaining dECM. 4.4 This standard provides a guide to the following steps in evaluating an extracellular matrix decellularization process: 4.4.1 Selecting attributes and test methods for characterization (Section 5) 4.4.2 Developing decellularization acceptance criteria for selected attributes (Section 6) 4.4.3 Documenting and analyzing the decellularization process flow (Section 7) 4.4.4 Performing a characterization of the decellularization process by testing decellularized ECM materials using the selected attributes, methods, and acceptance criteria (Section 8) 4.5  Decellularization processes vary widely in practice, utilizing a variety of reagents, temperatures, pressures, and/or mechanical forces in parallel and/or in sequence. While any one factor may act through consistent mechanisms, its effect will vary according to the decellularization process in its entirety as well as the particular tissue structure. As such, each part of a decellularization process should be understood and analyzed within the context of the complete process sequence and its action upon the type of tissue. For example, a process developed for dermis will likely not translate directly to a heart valve and the doubling of process time will affect each process differently, so the decellularization process will have to be adjusted to account for the difference in tissue properties and desired attributes at the conclusion of the process. Within the context of this guide, analysis of a processing step should not suggest material testing. Analysis is meant to demonstrate an understanding of the relevant mechanisms of decellularization and the relevant mechanisms of adverse effects on the ECM material. 4.6 Decellularization acceptance criteria and ECM integrity acceptance criteria should be developed based on the intended use of the dECM material. This guide suggests some considerations that should be used to develop and justify acceptance criteria. 4.6.1 Decellularization acceptance criteria already established for a source ECM and decellularization process allow for controlled changes to the decellularization process. Significant changes include changes to the processing mechanisms, reagents/materials, reagent concentrations, and controls as well as changes in source ECM materials. Prior to any significant change to a decellularization process, a decellularization process analysis should be conducted on the process steps which are subject to change. In addition, testing against the established decellularization acceptance criteria should be conducted on dECM material produced with the proposed process changes. A risk management process may then be utilized to ensure that any risks associated with the proposed changes are acceptable. 4.7 Measurements of decellularization attributes using the source extracellular matrix material as a reference can provide a valuable frame of reference and determination of percent change for exploratory and informational purposes. However, acceptance criteria based on percent change from the source material are more prone to variability in the final product due to variability in the source material. Acceptance criteria based on measurements of the dECM alone are more stable and simpler to implement. 4.7.1 The preparation of decellularized medical products involves variability originating in the source material as well as the processing; both types of variability can affect the consistency of the end product (dECM) and its performance in meeting predetermined acceptance criteria. A complete characterization of a decellularization process will include statistical ranges for each measured attribute. Statistical correlations may be explored to connect variation in source material and processing to end product attributes. These correlations can help prioritize source material and process controls to address uncontrolled variability.
  • Data de criação/publicação: 2019
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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