ASTM F3354-19
(Guide)Standard Guide for Evaluating Extracellular Matrix Decellularization Processes
Standard Guide for Evaluating Extracellular Matrix Decellularization Processes
SIGNIFICANCE AND USE
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 le...
SCOPE
1.1 This document provides guidance on the characterization and evaluation of the decellularization processes used to produce decellularized extracellular matrix (dECM) materials which will be used as medical products in direct or indirect contact with the body. The decellularization process may be performed on tissue from human or other mammalian sources or produced in vitro from human or other mammalian cells. The dECM may or may not be recellularized prior to use. Decellularized ECM material derived from non-mammalian tissue or cells and decellularized ECM material used for non-medical purposes may follow the framework provided but may require additional considerations outside the scope of this document.
1.2 Biological tissues are composed of a structural extracellular matrix (ECM) and embedded cells. The intent of a decellularization process is to disrupt and/or remove cells and cellular components from an ECM material while maintaining key structural and/or compositional properties of the material. Decellularization comprises process steps intended or expected to result or aid in the disruption of source tissue cells and/or removal of cellular content from the material undergoing decellularization. Actions that are intended to rinse or otherwise remove decellularization reagents or by-products should also be considered in that context as part of the decellularization process. Purifications or other isolations of specific ECM components are not considered decellularization and are outside the scope of this document.
1.3 This document describes relevant parameters of decellularization processes used to prepare extracellular matrix materials as medical products.
1.4 This document provides guidance on the measurement of specific and general properties of dECM. This includes both the analysis of cellular material as well as the assessment of the effects of decellularization on dECM properties such as composition...
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Standards Content (Sample)
This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: F3354 − 19
Standard Guide for
1
Evaluating Extracellular Matrix Decellularization Processes
This standard is issued under the fixed designation F3354; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope 1.5 This document does not provide guidance on the assess-
ment of the host response subsequent to the implantation or
1.1 This document provides guidance on the characteriza-
other in vivo placement of dECM medical products. Such
tion and evaluation of the decellularization processes used to
assessments should instead be conducted as part of biocom-
produce decellularized extracellular matrix (dECM) materials
patibility studies or other safety and efficacy studies. At a
which will be used as medical products in direct or indirect
minimum it is recommended that the finished product com-
contact with the body. The decellularization process may be
posed of dECM material shall be assessed in a relevant model
performed on tissue from human or other mammalian sources
that represents the biological responses that the product is
or produced in vitro from human or other mammalian cells.
expected to experience to ensure that the final material is
The dECM may or may not be recellularized prior to use.
functioning in accordance with design intentions. An in vivo
Decellularized ECM material derived from non-mammalian
model will generally be used, but cellular or ex vivo models
tissue or cells and decellularized ECM material used for
may also be satisfactory when appropriate.
non-medical purposes may follow the framework provided but
may require additional considerations outside the scope of this
1.6 This document provides guidance on determining perti-
document.
nent quality attributes as well as developing and assessing
1.2 Biological tissues are composed of a structural extracel- acceptancecriteriarelatedtoensuringtheconsistentevaluation
lular matrix (ECM) and embedded cells. The intent of a and use of decellularization in manufacturing medical prod-
decellularization process is to disrupt and/or remove cells and ucts. Acceptance criteria should address the adequacy of
cellular components from an ECM material while maintaining
cellular disruption and removal of cellular remnants. Accep-
key structural and/or compositional properties of the material.
tance criteria should define acceptable levels for retention of
Decellularizationcomprisesprocessstepsintendedorexpected
extracellular matrix components. Acceptance criteria may
to result or aid in the disruption of source tissue cells and/or
place limits on damage to retained components. Acceptance
removal of cellular content from the material undergoing
criteria should place limits on the persistence of decellulariza-
decellularization. Actions that are intended to rinse or other-
tion reagents. This document also provides recommendations
wise remove decellularization reagents or by-products should
on developing process parameters and associated process
also be considered in that context as part of the decellulariza-
controls.
tion process. Purifications or other isolations of specific ECM
1.6.1 This guide recommends attributes as representative
components are not considered decellularization and are out-
measures of decellularization in the direct function of remov-
side the scope of this document.
ingcellsandcellcomponents.Theseattributescanalsobeused
1.3 This document describes relevant parameters of decel- to show process consistency, capability, or equivalency. Rec-
lularization processes used to prepare extracellular matrix
ommendation of these attributes does not confer additional
materials as medical products.
significance related to product safety and performance.
1.6.2 No consensus has been established regarding decellu-
1.4 This document provides guidance on the measurement
larization thresholds or classifications. This guide therefore
of specific and general properties of dECM.This includes both
cannot suggest acceptance criteria and instead recommends
theanalysisofcellularmaterialaswellastheassessmentofthe
commonly measured attributes to develop acceptance criteria
effects of decellularization on dECM properties such as
specific to the design of each unique material and its intended
composition, structure, and material properties.
use.
1.7 Decellularized products will require evidence of safety
1
This guide is under the jurisdiction of ASTM Committee F04 on Medical and
and/or efficacy
...
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