ASTM F3163-22

Standard Guide for Categories and Terminology of Cellular and/or Tissue-Based Products (CTPs) for Skin Wounds

SIGNIFICANCE AND USE
4.1 This guide provides definitions and a classification for CTPs, as well as definitions related to skin tissue, skin wounds and ulcers, wound healing physiology, wound covers, and related medical and surgical procedures. This guide is not intended to prescribe or limit the clinical uses of these products.  
4.2 One objective of the current guide is to include the wide range of CTPs for which there is a rationale for benefit beyond that achievable with conventional wound coverings. Whether an individual CTP is capable of promoting wound healing must be determined by adequate evidence and is beyond the scope of this standard. Given that some of the materials used in dressings and skin substitutes (defined in Guide F2311) are the same as those used in CTPs, there has been confusion as to how to classify these products.  
4.3 This guide is distinguished from Guide F2311, which defines terminology and provides classification by clinical use for products that can be substituted for tissue grafts of human or animal tissue in medical and surgical therapies of skin lesions. In contrast, this guide defines terminology for description of CTPs for skin wounds; CTPs are defined primarily by their composition. Neither guide establishes a correspondence between device structure and clinical function.
SCOPE
1.1 This guide defines terminology for description of cellular and/or tissue-based products (CTPs) for skin wounds. CTPs are TEMPs (tissue-engineered medical products) that are primarily defined by their composition and comprise viable and/or nonviable human or animal cells, viable and/or nonviable tissues, and may include extracellular matrix components. CTPs may additionally include synthetic components.  
1.2 This guide also describes categories and terminology for CTPs based on their composition. This systematic categorization is not intended to be prescriptive for product labeling, and it describes only the most salient characteristics of these products; the actual biological and clinical functions can depend on characteristics not recognized in the categorization and it should be understood that two products that can be described identically by the categorization should not be presumed to be identical or have the same clinical utility.  
1.3 This guide defines CTP-related terminology in the context of skin wounds. However, this guide does not provide a correspondence between the CTP composition and its clinical use(s). More than one product may be suitable for each clinical use, and one product may have more than one clinical use.  
1.4 This guide does not purport to address safety concerns with the use of CTPs. It is the responsibility of the user of this standard to establish appropriate safety and health practices involved in the development of said products in accordance with applicable regulatory guidance documents and in implementing this guide to evaluate the cellular and/or tissue-based products for wounds.  
1.5 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.  
1.6 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.

General Information

• Status: Published
• Publication Date: 14-Feb-2022
• ICS: 11.120.20 - Wound dressings and compresses
• Technical Committee: F04 - Medical and Surgical Materials and Devices
• Drafting Committee: F04.41 - Classification and Terminology for TEMPs

Relations

• Refers: ASTM F2312-11(2020) - Standard Terminology Relating to Tissue Engineered Medical Products
• Effective Date: 01-Feb-2020
• Refers: ASTM F2150-19 - Standard Guide for Characterization and Testing of Biomaterial Scaffolds Used in Regenerative Medicine and Tissue-Engineered Medical Products
• Effective Date: 01-Oct-2019
• Refers: ASTM F2739-19 - Standard Guide for Quantifying Cell Viability and Related Attributes within Biomaterial Scaffolds
• Effective Date: 01-Sep-2019
• Refers: ASTM F2739-16 - Standard Guide for Quantifying Cell Viability within Biomaterial Scaffolds
• Effective Date: 01-Oct-2016
• Refers: ASTM F2027-16 - Standard Guide for Characterization and Testing of Raw or Starting Materials for Tissue-Engineered Medical Products
• Effective Date: 01-Oct-2016
• Refers: ASTM F2150-13 - Standard Guide for Characterization and Testing of Biomaterial Scaffolds Used in Tissue-Engineered Medical Products
• Effective Date: 01-Oct-2013
• Refers: ASTM F2312-11 - Standard Terminology Relating to Tissue Engineered Medical Products
• Effective Date: 01-Apr-2011
• Refers: ASTM F2312-10 - Standard Terminology Relating to Tissue Engineered Medical Products
• Effective Date: 01-Jun-2010
• Refers: ASTM F2311-08 - Standard Guide for Classification of Therapeutic Skin Substitutes (Withdrawn 2017)
• Effective Date: 01-Oct-2008
• Refers: ASTM F2739-08 - Standard Guide for Quantitating Cell Viability Within Biomaterial Scaffolds
• Effective Date: 01-Aug-2008
• Refers: ASTM F2027-08 - Standard Guide for Characterization and Testing of Raw or Starting Biomaterials for Tissue-Engineered Medical Products
• Effective Date: 01-May-2008
• Refers: ASTM F2150-07 - Standard Guide for Characterization and Testing of Biomaterial Scaffolds Used in Tissue-Engineered Medical Products
• Effective Date: 01-Dec-2007
• Refers: ASTM F2311-06 - Standard Guide for Classification of Therapeutic Skin Substitutes
• Effective Date: 01-May-2006
• Refers: ASTM F2312-04 - Standard Terminology Relating to Tissue Engineered Medical Products
• Effective Date: 01-Nov-2004
• Refers: ASTM F2312-03 - Standard Terminology Relating to Tissue Engineered Medical Products
• Effective Date: 10-Sep-2003

Overview

ASTM F3163-22: Standard Guide for Categories and Terminology of Cellular and/or Tissue-Based Products (CTPs) for Skin Wounds provides a comprehensive classification and standardized terminology for the description of CTPs. Developed by ASTM International, this guide supports clarity and consistency for manufacturers, regulators, clinicians, and researchers involved in skin wound management. The standard focuses on definitions and classification based on product composition, detailing terms related to skin tissue, wounds, wound healing, wound covers, and related clinical procedures. Although it does not prescribe product labeling or clinical use, it is a critical reference for professionals engaged with advanced wound care products.

Key Topics

• Comprehensive Definitions: The guide establishes standard terminology for CTPs, encompassing components such as cells (viable, nonviable, or killed), tissues (human or animal), and extracellular matrix materials. It also clarifies terms commonly used in wound care and tissue engineering.
• Classification by Composition: CTPs are primarily categorized by composition, not clinical function. Categories include biosynthetic, non-living tissue-based (human or animal), and living cell biological (minimally processed or cultured).
• Cell Viability and Activity: Five levels of cell viability are described: acellular, killed cells, non-viable cells, viable cells, and proliferation competent cells. This aids in clear differentiation between products based on cellular function.
• Component-Based Categorization: Guidelines are given for naming CTPs by specifying key cell and scaffold characteristics, such as species of origin, cell type, and scaffold material (natural or synthetic).
• Wound Care Terminology: Standardized terms for various wound types (e.g., acute wounds, chronic wounds, ulcers, burns, pressure injuries) and healing processes are defined to ensure consistency across clinical and research settings.
• Sterility Categorization: The standard recognizes two sterility categories-sterile and aseptic-highlighting relevant ISO standards for sterility assurance.

Applications

• Product Development: Developers of tissue-engineered medical products can use this guide to ensure their documentation and labeling align with international best practices for describing CTPs.
• Regulatory Submissions: Standardized terminology and categories facilitate clearer communication with regulatory agencies during product review and approval processes.
• Clinical Communication: Healthcare providers benefit from common language, which aids in the selection and comparison of advanced wound care products for specific clinical needs.
• Research and Education: Researchers and educators can refer to this standard for precise definitions and product classifications, supporting robust study design and educational programs in regenerative medicine and wound care.
• Procurement and Supply Chain: Buyers and supply chain professionals rely on standardized descriptors to correctly identify and requisition products suitable for particular clinical applications.

Related Standards

• ASTM F2311: Guide for Classification of Therapeutic Skin Substitutes (clinical use-based classification)
• ASTM F2027: Guide for Characterization and Testing of Raw or Starting Materials for Tissue-Engineered Medical Products
• ASTM F2150: Guide for Characterization and Testing of Biomaterial Scaffolds Used in Regenerative Medicine and Tissue-Engineered Medical Products
• ASTM F2312: Terminology Relating to Tissue-Engineered Medical Products
• ASTM F2739: Guide for Quantifying Cell Viability and Related Attributes within Biomaterial Scaffolds
• Relevant ISO Sterility Standards: ISO 11135, 11137, 13408, and others for sterility and aseptic processing

Practical Value

Adopting ASTM F3163-22 enhances communication and reduces ambiguity in the rapidly evolving field of cellular and/or tissue-based products for skin wounds. By providing a systematic classification and clear terminology, this standard supports innovation, regulatory compliance, patient safety, and improved wound care outcomes.

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: F3163 − 22
Standard Guide for
Categories and Terminology of Cellular and/or Tissue-Based
Products (CTPs) for Skin Wounds
This standard is issued under the fixed designation F3163; 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* 1.6 This international standard was developed in accor-
dance with internationally recognized principles on standard-
1.1 This guide defines terminology for description of cellu-
ization established in the Decision on Principles for the
lar and/or tissue-based products (CTPs) for skin wounds. CTPs
Development of International Standards, Guides and Recom-
are TEMPs (tissue-engineered medical products) that are
mendations issued by the World Trade Organization Technical
primarily defined by their composition and comprise viable
Barriers to Trade (TBT) Committee.
and/or nonviable human or animal cells, viable and/or nonvi-
able tissues, and may include extracellular matrix components.
2. Referenced Documents
CTPs may additionally include synthetic components.
2.1 ASTM Standards:
1.2 Thisguidealsodescribescategoriesandterminologyfor
F2027 Guide for Characterization and Testing of Raw or
CTPs based on their composition. This systematic categoriza-
Starting Materials for Tissue-Engineered Medical Prod-
tion is not intended to be prescriptive for product labeling, and
ucts
it describes only the most salient characteristics of these
F2150 Guide for Characterization and Testing of Biomate-
products; the actual biological and clinical functions can
rial Scaffolds Used in Regenerative Medicine and Tissue-
depend on characteristics not recognized in the categorization
Engineered Medical Products
and it should be understood that two products that can be
F2311 Guide for Classification of Therapeutic Skin Substi-
described identically by the categorization should not be 3
tutes (Withdrawn 2017)
presumed to be identical or have the same clinical utility.
F2312 Terminology Relating to Tissue Engineered Medical
1.3 This guide defines CTP-related terminology in the
Products
context of skin wounds. However, this guide does not provide F2739 Guide for Quantifying Cell Viability and Related
acorrespondencebetweentheCTPcompositionanditsclinical
Attributes within Biomaterial Scaffolds
use(s). More than one product may be suitable for each clinical
3. Terminology
use, and one product may have more than one clinical use.
3.1 Skin Tissue Definitions:
1.4 This guide does not purport to address safety concerns
3.1.1 dermal, adj—pertaining to the dermis (1).
with the use of CTPs. It is the responsibility of the user of this
standard to establish appropriate safety and health practices
3.1.2 dermis, n—the layer of the skin underneath the
involved in the development of said products in accordance epidermis,consistingofadensebedofvascularizedconnective
with applicable regulatory guidance documents and in imple-
tissue (1).
menting this guide to evaluate the cellular and/or tissue-based
3.1.3 dermoepidermal junction (DEJ), n—distinct anatomic
products for wounds.
zone between the epidermis and dermis that facilitates adher-
1.5 This standard does not purport to address all of the ence between the two layers; contains laminin, collagen type
safety concerns, if any, associated with its use. It is the
VII, collagen type IV, and tenascin C (2).
responsibility of the user of this standard to establish appro-
3.1.4 epidermal, adj—pertaining to or resembling epidermis
priate safety, health, and environmental practices and deter-
(1).
mine the applicability of regulatory limitations prior to use.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM
This guide is under the jurisdiction of ASTM Committee F04 on Medical and Standards volume information, refer to the standard’s Document Summary page on
Surgical Materials and Devices and is the direct responsibility of Subcommittee the ASTM website.
F04.41 on Classification and Terminology for TEMPs. The last approved version of this historical standard is referenced on
Current edition approved Feb. 15, 2022. Published March 2022. Originally www.astm.org.
approved in 2016. Last previous edition approved in 2016 as F3163 – 16. DOI: The boldface numbers in parentheses refer to the list of references at the end of
10.1520/F3163-22. this standard.
*A Summary of Changes section appears at the end of this standard
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F3163 − 22
3.1.5 epidermis, n—the outermost and nonvascularized epidermal cells from which the wound can heal spontaneously
layer of the skin (1). by epidermal tissue regeneration.
3.1.6 extracellular matrix, n—a structural and functional
3.2.11 pressure injury/ulcer, n—localized injury to the skin
entity produced by cells that surrounds and supports cells and
and/or underlying tissue usually over a bony prominence as a
regulates cell communication. Typical components are
result of pressure, or pressure in combination with shear. Also
collagens, adhesive glycoproteins, glycosaminoglycans, and known as decubital ulcer, decubitus ulcer, pressure sore,or
proteoglycans (3).
bed sore (8).
3.1.7 skin, n—the outer integument or covering of the body,
3.2.12 scar, n—fibrous tissue replacing normal tissues de-
consisting of the dermis and the epidermis, and resting upon
stroyed by injury or disease.
the subcutaneous tissue.
3.2.13 surgical wound, n—a wound created as the result of
3.1.8 tissue, n—a level of organization in multicellular
a surgical procedure.
organismsconsistingofagroupofstructurallyandfunctionally
3.2.14 ulcer, n—a local defect, or excavation of the surface
related cells and extracellular matrix. (F2312)
of an organ or tissue, which is produced by the sloughing of
3.2 Skin Wound and Ulcer Definitions:
inflammatory necrotic tissue.
3.2.1 acute wound, n—a wound that normally proceeds
3.2.15 venous leg ulcer, n—a local defect on the leg due to
through an orderly and timely reparative/regenerative process
chronic venous insufficiency. Also known as a venous stasis
that results in sustained restoration of anatomic and functional
ulcer or a venous insufficiency ulcer (5, 6).
integrity (4).
3.2.16 wound, n—an acquired disruption of normal ana-
3.2.2 arterial ulcer, n—also referred to as ischemic ulcer,is
tomic structure and function of a tissue or organ. Also known
caused by poor perfusion (delivery of nutrient-rich blood) to
as injury or trauma (4).
the lower extremities (5, 6).
3.3 Wound Healing Physiology Definitions:
3.2.3 burn, n—injury to tissues caused by contact with heat,
3.3.1 Acute wound healing of skin typically proceeds in a
chemicals, electricity, friction, or radiant and electromagnetic
sequential series of steps that overlap in time: hemostasis,
energy (1).
inflammation, new tissue formation (re-epithelialization,
3.2.4 chronic wound, n—a wound that has failed to proceed
granulation tissue formation, neovascularization), and tissue
throughanorderlyandtimelyprocesstoproduceanatomicand
remodeling (wound contraction and extracellular matrix reor-
functional integrity, or proceeded through the repair process
ganization). Each of these steps is characterized by dynamic,
without establishing a sustained anatomic and functional result
reciprocal interactions among cells, extracellular matrix, and
(4).
the cellular microenvironment. In contrast, chronic wounds do
3.2.5 diabetic leg or foot ulcer, n—a break of the skin of the
not proceed normally through these healing steps but instead
foot that includes minimally the epidermis and part of the
exhibit numerous abnormalities as a result of underlying
dermis and involves infection, ulceration, or destruction of
pathobiology (9, 10).
tissuesofthefootassociatedwithneuropathyand/orperipheral
3.3.2 granulation tissue, n—the newly formed vascular
arterydiseaseinthelowerextremityofapersonwith(ahistory
tissue normally produced in the healing of wounds of soft
of) diabetes mellitus (5, 6).
tissue and ultimately forming the cicatrix (scar); it consists of
3.2.6 full-thickness skin wound, n—a skin wound with the small, translucent, red, nodular masses or granulations that
loss of or penetration through the epidermis and all the dermis,
have a velvety appearance.
or at least the depth of dermis that includes most or all sources
3.3.3 heal, v—to restore wounded parts or to make healthy.
of epidermal cells from epidermal adnexae (glands and fol-
3.3.4 healing, n—the restoration of integrity to injured
licles).
tissue.
3.2.7 ischemic ulcer, n—see arterial ulcer.
3.3.5 necrotic, adj—characterized by the sum of the mor-
3.2.8 lesion, n—any pathological or traumatic discontinuity
phological changes indicative of cell death and caused by the
of tissue or loss of function of a tissue part.
progressive degradative action of enzymes (1).
3.2.9 mixed arterial-venous ulcer, n—an ulceration due to a
3.3.6 scar, n—fibrous tissue replacing normal tissues de-
combination of chronic venous insufficiency and arterial dis-
stroyed by injury or disease.
ease (7).
3.3.7 tissue regeneration, n—healing in which lost tissue is
3.2.10 partial thickness skin wound, n—a skin wound with
replacedbymigration,differentiation,andproliferationofcells
the loss of the epidermis and part of the dermis, but retaining
that deposit new extracellular matrix with normal architecture,
a layer of viable dermal tissue that includes the sources of
function, and appearance.
3.3.8 tissue repair, n—healing in which lost tissue is re-
placed by a fibrous scar, which is produced from granulation
In this guide, skin wounds include those caused by burns, trauma, surgical
incision, or surgical excision, in addition to ulcers associated with underlying tissue.
chronic conditions.This guide makes no distinction among different types of ulcers,
3.3.9 wound contraction, n—the shrinkage and spontaneous
which are a result of differing pathologies or conditions and for which different
procedures and different types of CTPs may be appropriate. closure of open skin wounds.
F3163 − 22
3.3.10 wound contracture, n—a condition of fixed high 3.5.13 cellular and/or tissue-based products (CTPs),
resistance to passive stretch of muscle, skin, or joints resulting n—TEMPs (tissue-engineered medical products) that are pri-
from fibrosis and scarring of the skin or the tissues supporting marilydefinedbytheircompositionandcompriseviableand/or
the muscles or the joints, or both. nonviable human or animal cells, viable and/or nonviable
tissues, and may include extracellular matrix components.
3.3.11 wound inflammation, n—a localized protective re-
CTPs may additionally include synthetic components.
sponse elicited by injury or destruction of tissues, which serves
to destroy, dilute, or wall off (sequester) both the injurious 3.5.14 cellular therapy, n—a treatment containing viable
agent and the injured tissue. It is characterized in the acute (living) cells.
formbytheclassicalsignsofpain(dolor),heat(calor),redness
3.5.15 cellularized scaffold, n—a scaffold that has been
(rubor), swelling (tumor), and loss of function (functio laesa).
seeded with viable cells. The seeded scaffold may or may not
Histologically,itinvolvesacomplexseriesofevents,including
be further cultured.
dilation of arterioles, capillaries, and venules, with increased
3.5.16 CTP product format, n—the overall shape or appear-
permeability and blood flow; exudation of fluids, including
ance of the CTP, which includes, but is not limited to: single
plasma proteins; and leukocytic migration into the inflamma-
sheets, multilayer sheets, three-dimensional constructs, par-
tory focus.
ticles (for example, powders), granules, gels, sprays, pellets,
3.4 Wound Cover Definitions:
spheroids, cylinders, and so forth.
3.4.1 dressing, n—any of various materials utilized to cover
3.5.17 cultured cells, n—cells propagated by cell culture.
and protect wounds.
3.5.18 decellularized scaffold, n—an acellular scaffold
3.4.2 surgical dressing, n—any of various materials utilized
formed by removing the cells from an extracellular matrix by
to cover and protect wounds following surgical procedures or
chemical and physical treatments.
debridement of any type.
3.5.19 devitalized scaffold, n—atissue-derivedscaffoldcon-
3.5 CTP Components and Methods:
taining killed cells and no viable cells.
3.5.1 acellular scaffold, n—a scaffold without primary or
3.5.20 differentiated cell, n—cell with morphological and
cultured cells.
metabolic characteristics of a specialized type.
3.5.2 allogeneic or allogenic, adj—from cells, tissues, and
3.5.21 extracellular matrix architecture, n—structural char-
organs in which the donor and recipient are genetically
acteristics of an extracellular matrix.
different individuals of the same species.
3.5.22 killed cell, n—a cell that has been subjected to
3.5.3 autologous, adj—from cells, tissues, and organs in
physical or chemical conditions that ensure that it is nonviable.
which the donor and recipient is the same individual.
3.5.23 live cell, n—a viable cell.
3.5.4 bioactive agent, n—any molecular component that
3.5.24 metabolically active, adj—capable of catalyzing all
elicits a tissue or cell response.
of the chemical transformations and transport processes typical
3.5.5 biocompatible, adj—the ability of a material to per-
of living organisms, including anabolism and catabolism.
form with an appropriate host response in a specific situation
Metabolic processes typically transform small molecules, but
(11).
alsoincludemacromolecularprocessessuchasDNArepairand
3.5.6 biological, adj—synthesized or produced by living
replication, protein synthesis and degradation, and membrane
cells.
transport.
3.5.7 biomaterial, n—a synthetic or natural substance or
3.5.25 natural materials, n—synthesized or produced by
composite used for a biological or biomedical application.
living cells. (F2027)
(F2312)
3.5.26 nonviable cell, n—a cell that does not meet the
3.5.8 biosynthetic, adj—partly synthesized and/or produced
definition of viability specified in 3.5.35.
by living cells and partly chemically synthesized.
3.5.27 primary cells, n—dispersed cells derived directly
3.5.9 cell, n—the smallest structural and functional unit of a
from fresh tissue.
eukaryotic organism. Typically, cells are microscopic and
3.5.28 processed, adj—characterized by a series of me-
consist of cytoplasm and a nucleus enclosed in a membrane
chanical or chemical operations on a substance in order to
(12).
change or preserve it. In this standard, processed is used to
3.5.10 cell culture, n—the in vitro growth or maintenance of
refer to tissue (as in processed tissue) (12).
cells.
3.5.29 proliferation competent cell, n—cell capable of rep-
3.5.11 cell type, n—a distinct morphological or functional
lication.
form of cell that expresses similar genes.
3.5.30 scaffold, n—a support, delivery vehicle, or matrix for
3.5.12 cellular, adj—containing viable (living) cells.
facilitating the migration, binding, or transport of cells or
This definition is a modification of Dorland’s definition of contracture, “a Guidance regulated by (1) CBER under Section 361 of the PHS Act and 21
condition of fixed high resistance to passive stretch of muscle, resulting from CFR Part 1271, (2) CBER as drugs, devices, and/or biological products subject to
fibrosisofthetissuessupportingthemusclesorthejoints,ordisordersofthemuscle Section 351 of the PHSAct and/or theAct and applicable regulations in Title 21 of
fibers,” (1) because that definition does not address fibrosis and scarring in skin. the CFR, or (3) CDRH under the FD&C Act as a medical device.
F3163 − 22
bioactive molecules used to replace, repair, or regenerate excision of open skin
...

This document is not an ASTM standard and is intended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation: F3163 − 16 F3163 − 22
Standard Guide for
Classification Categories and Terminology of Cellular and/or
Tissue-Based Products (CTPs) for Skin Wounds
This standard is issued under the fixed designation F3163; 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 Scope*
1.1 This guide defines terminology for description of cellular and/or tissue-based products (CTPs) for skin wounds. CTPs are
defined primarily TEMPs (tissue-engineered medical products) that are primarily defined by their composition and comprise cells
and/or the extracellular components of tissue. CTPs may contain cells (viable or nonviable), tissues, proteins, and other materials
for which there is a rationale for benefit beyond that achievable with conventional wound coverings. viable and/or nonviable
human or animal cells, viable and/or nonviable tissues, and may include extracellular matrix components. CTPs may additionally
include synthetic components. Whether an individual CTP is capable of promoting wound healing must be determined by adequate
evidence and is beyond the scope of this standard.
1.2 This guide also describes a classification categories and nomenclatureterminology for CTPs based on their composition. This
systematic nomenclaturecategorization is not intended to be prescriptive for product labeling, and it describes only the most salient
characteristics of these products; the actual biological and clinical functions can depend on characteristics not recognized in the
nomenclature,categorization and it should be understood that two products that can be described identically by the nomencla-
turecategorization should not be presumed to be identical or have the same clinical utility.
1.3 This guide defines CTP-related terminology in the context of skin wounds. However, this guide does not provide a
correspondence between the CTP composition and its clinical use(s). More than one product may be suitable for each clinical use,
and one product may have more than one clinical use.
1.4 This guide does not purport to address safety concerns with the use of CTPs. It is the responsibility of the user of this standard
to establish appropriate safety and health practices involved in the development of said products in accordance with applicable
regulatory guidance documents and in implementing this guide to evaluate the cellular and/or tissue-based products for wounds.
1.5 This standard does not purport to address safety concerns with the use of CTPs. all of the safety concerns, if any, associated
with its use. It is the responsibility of the user of this standard to establish appropriate safety safety, health, and
healthenvironmental practices and determine the applicability of regulatory limitations prior to use.
1.6 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.
This test method guide is under the jurisdiction of ASTM Committee F04 on Medical and Surgical Materials and Devices and is the direct responsibility of Subcommittee
F04.41 on Classification and Terminology for TEMPs.
Current edition approved Jan. 1, 2016Feb. 15, 2022. Published February 2016March 2022. Originally approved in 2016. Last previous edition approved in 2016 as
F3163 – 16. DOI: 10.1520/F3163-1610.1520/F3163-22.
*A Summary of Changes section appears at the end of this standard
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F3163 − 22
2. Referenced Documents
2.1 ASTM Standards:
F2027 Guide for Characterization and Testing of Raw or Starting Materials for Tissue-Engineered Medical Products
F2150 Guide for Characterization and Testing of Biomaterial Scaffolds Used in Regenerative Medicine and Tissue-Engineered
Medical Products
F2311 Guide for Classification of Therapeutic Skin Substitutes (Withdrawn 2017)
F2312 Terminology Relating to Tissue Engineered Medical Products
F2739 Guide for Quantifying Cell Viability and Related Attributes within Biomaterial Scaffolds
3. Terminology
3.1 Skin Tissue Definitions:
3.1.1 dermal, adj—pertaining to the dermis (1).
3.1.2 dermis, n—the layer of the skin deep to underneath the epidermis, consisting of a dense bed of vascularized connective tissue
(1).
3.1.3 dermoepidermal junction (DEJ), n—distinct anatomic zone between the epidermis and dermis that facilitates adherence
between the two layers; contains laminin, collagen type VII, collagen type IV, and tenascin C (2).
3.1.4 epidermal, adj—pertaining to or resembling epidermis (1).
3.1.5 epidermis, n—the outermost and nonvascularized layer of the skin (1).
3.1.6 extracellular matrix, n—a structural and functional entity produced by cells that surrounds and supports cells and regulates
cell communication. Typical components are collagens, adhesive glycoproteins, glycosaminoglycans, and proteoglycans (3).
3.1.7 skin, n—the outer integument or covering of the body, consisting of the dermis and the epidermis, and resting upon the
subcutaneous tissue. (F2312)
3.1.8 tissue, n—an aggregation of similarly specialized cells united in the performance of a particular function. A tissue contains
an extracellular matrix in addition to specialized cellsa level of organization in multicellular organisms consisting of a group of
structurally and functionally related cells and extracellular matrix. (F2312)
3.2 Skin Wound and Ulcer Definitions:
3.2.1 acute wound, n—a wound that normally proceeds through an orderly and timely reparative/regenerative process that results
in sustained restoration of anatomic and functional integrity (4).
3.2.2 arterial ulcer, n—ulceration duealso referred to peripheralas arterial diseaseischemic ulcer, is caused by poor perfusion
(delivery of nutrient-rich blood) to the lower extremities (5, 6).
3.2.3 burn, n—injury to tissues caused by contact with heat, chemicals, electricity, friction, or radiant and electromagnetic energy
(1).
3.2.4 chronic wound, n—a wound that has failed to proceed through an orderly and timely process to produce anatomic and
functional integrity, or proceeded through the repair process without establishing a sustained anatomic and functional result (4).
For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
The last approved version of this historical standard is referenced on www.astm.org.
The boldface numbers in parentheses refer to the list of references at the end of this standard.
In this guide, skin wounds include those caused by burns, trauma, surgical incision, or surgical excision, in addition to ulcers associated with underlying chronic
conditions. This guide makes no distinction among different types of ulcers, which are a result of differing pathologies or conditions and for which different procedures and
different types of CTPs may be appropriate.
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3.2.5 diabetic leg or foot ulcer, n—a break of the skin of the foot that includes minimally the epidermis and part of the dermis
and involves infection, ulceration, or destruction of tissues of the foot associated with neuropathy and/or peripheral artery disease
in the lower extremity of a person with (a history of) diabetes mellitus (5, 6).
3.2.6 full-thickness skin wound, n—a skin wound with the loss of or penetration through the epidermis and all of the dermis, or
at least the depth of dermis that includes most or all sources of epidermal cells from epidermal adnexae (glands and follicles).
(F2312)
3.2.7 ischemic ulcer, n—see arterial ulcer.
3.2.8 lesion, n—any pathological or traumatic discontinuity of tissue or loss of function of a tissue part. (F2312)
3.2.9 mixed arterial-venous ulcer, n—an ulceration due to a combination of chronic venous insufficiency and arterial disease (57).
3.2.10 partial thickness skin wound, n—a skin wound with the loss of the epidermis and part of the dermis, but retaining a layer
of viable dermal tissue that includes the sources of epidermal cells from which the wound can heal spontaneously by epidermal
tissue regeneration. (F2312)
3.2.11 pressure injury/ulcer, n—localized injury to the skin and/or underlying tissue usually over a bony prominence as a result
of pressure, or pressure in combination with shear. Also known as decubital ulcer,decubitus ulcer,pressure sore, or bed sore(8).
3.2.12 scar, n—fibrous tissue replacing normal tissues destroyed by injury or disease. (F2312)
3.2.13 surgical wound, n—a wound created as the result of a surgical procedure.
3.2.14 ulcer, n—a local defect, or excavation of the surface of an organ or tissue, which is produced by the sloughing of
inflammatory necrotic tissue. (F2312)
3.2.12 pressure ulcer, n—localized injury to the skin and/or underlying tissue usually over a bony prominence as a result of
pressure, or pressure in combination with shear and/or friction. Also known as decubital ulcer,decubitus ulcer,pressure sore,bed
sore(6).
3.2.13 diabetic ulcer, n—an ulcer, usually of the lower extremities and particularly of the foot, associated with diabetes mellitus
(1).
3.2.15 venous leg ulcer, n—ulceration a local defect on the leg due to chronic venous insufficiency. Also known as a venous stasis
ulcer or a venous insufficiency ulcer (5, 6).
3.2.16 wound, n—a an acquired disruption of normal anatomic structure and function of a tissue or organ. Also known as injury
or trauma (4).
3.2.15.1 Discussion—
In this guide, skin wounds include those caused by burns, trauma, surgical incision, or surgical excision, in addition to ulcers
associated with underlying chronic conditions. This guide makes no distinction among different types of ulcers, which are a result
of differing pathologies or conditions and for which different procedures and different types of CTPs may be appropriate.
3.3 Wound Healing Physiology Definitions:
3.3.1 Acute wound healing of skin typically proceeds in a sequential series of steps that overlap in time: hemostasis, inflammation,
new tissue formation (re-epithelialization, granulation tissue formation, neovascularization), and tissue remodeling (wound
contraction and extracellular matrix reorganization). Each of these steps is characterized by dynamic, reciprocal interactions among
cells, extracellular matrix, and the cellular microenvironment. In contrast, chronic wounds do not proceed normally through these
healing steps but instead exhibit numerous abnormalities as a result of underlying pathobiology (79, 810).
3.3.2 granulation tissue, n—the newly formed vascular tissue normally produced in the healing of wounds of soft tissue and
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ultimately forming the cicatrix [scar];(scar); it consists of small, translucent, red, nodular masses or granulations that have a velvety
appearance. (F2312)
3.3.3 heal, v—to restore wounded parts or to make healthy. (F2312)
3.3.4 healing, n—the restoration of integrity to injured tissue. (F2312)
3.3.5 necrotic, adj—characterized by the sum of the morphological changes indicative of cell death and caused by the progressive
degradative action of enzymes (1).
3.3.6 scar, n—fibrous tissue replacing normal tissues destroyed by injury or disease. (F2312)
3.3.7 tissue regeneration, n—healing in which lost tissue is replaced by migration, differentiation, and proliferation of cells that
deposit new extracellular matrix with normal architecture, function, and appearance.
3.3.8 tissue repair, n—healing in which lost tissue is replaced by a fibrous scar, which is produced from granulation tissue. (F2312)
3.3.9 wound contraction, n—the shrinkage and spontaneous closure of open skin wounds. (F2312)
3.3.10 wound contracture, n—a condition of fixed high resistance to passive stretch of muscle, skin, or joints resulting from
fibrosis and scarring of the skin or the tissues supporting the muscles or the joints, or both.
3.3.10.1 Discussion—
This definition is a modification of Dorland’s definition of contracture, “a condition of fixed high resistance to passive stretch of
muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or disorders of the muscle fibers,” (1) because
that definition does not address fibrosis and scarring in skin. (F2312)
3.3.11 wound inflammation, n—a localized protective response elicited by injury or destruction of tissues, which serves to destroy,
dilute, or wall off (sequester) both the injurious agent and the injured tissue. It is characterized in the acute form by the classical
signs of pain (dolor), heat (calor)), redness (rubor), swelling (tumor), and loss of function (functio laesa). Histologically, it
involves a complex series of events, including dilation of arterioles, capillaries, and venules, with increased permeability and blood
flow; exudation of fluids, including plasma proteins; and leukocytic migration into the inflammatory focus. (F2312)
3.4 Wound Cover Definitions:
3.4.1 dressing, n—any of various materials utilized to cover and protect wounds. (F2312)
3.4.2 surgical dressing, n—any of various materials utilized to cover and protect wounds following surgical procedures or
debridement of any type.
3.5 CTP Components and Methods:
3.5.1 acellular scaffold, n—a scaffold without primary or cultured cells. (F2311)
3.5.2 allogeneic or allogenic, adj—from cells, tissues, and organs in which the donor and recipient are genetically different
individuals of the same species. (F2311)
3.5.3 autologous, adj—from cells, tissues, and organs in which the donor and recipient is the same individual. (F2311)
3.5.4 bioactive agent, n—any molecular component that elicits a tissue or cell response.
3.5.5 biocompatible, adj—the ability of a material to perform with an appropriate host response in a specific situation (911).
3.5.6 biological, adj—synthesized or produced by living cells.
This definition is a modification of Dorland’s definition of contracture, “a condition of fixed high resistance to passive stretch of muscle, resulting from fibrosis of the
tissues supporting the muscles or the joints, or disorders of the muscle fibers,” (1) because that definition does not address fibrosis and scarring in skin.
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3.5.7 biomaterial, n—any substance (other than a drug), synthetic or natural, that can be used as a system or part of a system that
treats, augments, or replaces any tissue, organ, or function of the body.a synthetic or natural substance or composite used for a
biological or biomedical application. (F2312)
3.5.8 biosynthetic, adj—partly synthesized orand/or produced by living cells and partly chemically synthesized.
3.5.9 cell, n—the smallest structural and functional unit of an a eukaryotic organism. Typically, cells are microscopic and consist
of cytoplasm and a nucleus enclosed in a membrane (1012).
3.5.10 cell culture, n—the in vitro growth or maintenance of cells. (F2311)
3.5.11 cell type, n—a distinct morphological or functional form of cell.cell that expresses similar genes. (F2311)
3.5.12 cellular, adj—containing viable (living) cells.
3.5.13 cellular and/or tissue-based product (CTP),products (CTPs), n—a product defined primarily by its composition, comprising
cells and/or the extracellular components of tissue. CTPs may contain cells (viable or nonviable), tissues, proteins, and other
materials for which there is a rationale for benefit beyond that achievable with conventional wound coverings. TEMPs
(tissue-engineered medical products) that are primarily defined by their composition and comprise viable and/or nonviable human
or animal cells, viable and/or nonviable tissues, and may include extracellular matrix components. CTPs may additionally include
synthetic components.Whether an individual CTP is capable of promoting wound healing must be determined by adequate
evidence and is beyond the scope of this standard.
3.5.14 cellular therapy, n—a treatment containing viable (living) cells.
3.5.15 cellularized scaffold, n—a scaffold that has been seeded with viable cells. The seeded scaffold may or may not be further
cultured. (F2311)
3.5.16 CTP product format, n—the overall shape or appearance of the CTP, which includes, but is not limited to,to: single sheets,
multilayer sheets, 3-dimensionalthree-dimensional constructs, particles (e.g., (for example, powders), granules, gels, sprays,
pellets, spheroids, cylinders, and so forth.
3.5.17 cultured cells, n—cells propagated by cell culture. (F2311)
3.5.18 decellularized scaffold, n—an acellular scaffold formed by removing the cells from an extracellular matrix by chemical and
physical treatments. (F2311)
3.5.19 devitalized scaffold, n—a tissue-derived scaffold containing killed cells and no viable cells.
3.5.20 differentiated cell, n—cell with morphological and metabolic characteristics of a specialized type.
3.5.21 extracellular matrix architecture, n—structural characteristics of an extracellular matrix.
3.5.22 killed cell, n—a cell that has been subjected to physical or chemical conditions that assureensure that it is
non-viable.nonviable. (F2311)
3.5.23 live cell, n—a viable cell. (F2311)
3.5.24 metabolically active, adj—capable of catalyzing all of the chemical transformations and transport processes typical of living
organisms, including anabolism and catabolism. Metabolic processes typically transform small molecules, but also include
Guidance regulated by (1) CBER under Section 361 of the PHS Act and 21 CFR Part 1271, (2) CBER as drugs, devices, and/or biological products subject to Section
351 of the PHS Act and/or the Act and applicable regulations in Title 21 of the CFR, or (3) CDRH under the FD&C Act as a medical device.
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macromolecular processes such as DNA repair and replication, protein synthesis and degradation, and membrane transport.
(F2311)
3.5.25 natural materials, n—synthesized or produced by living cells. (F2027)
3.5.26 non-viablenonviable cell, n—a cell that does not meet the definition of viability specified in 3.5.35. (F2311)
3.5.27 primary cells, n—dispersed cells derived directly from fresh tissue. (F2311)
3.5.28 processed, adj—characterized by a series of mechanical or chemical operations on (something) a substance in order to
change or preserve it. In this standard, processed is used to refer to tissue (as in processed tissue) (1012).
3.5.29 proliferation competent cell, n—cell capable of replication.
3.5.30 scaffold, n—a support, delivery vehicle, or matrix for facilitating the migration, binding, or transport of cells or bioactive
molecules used to replace, repair, or regenerate tissues. (F2150)
3.5.31 scaffold architecture, n—macrostructural characteristics of a scaffold biomaterial that determines its permeability to cells,
including whether or not it is a/anan impervious solid, impervious membrane, porous membrane, open cell open-cell porous foam,
non-wovennonwoven fiber, woven fabric, or cell-permeable gel. (F2311)
3.5.32 stem cell, n—a cell that can replicate itself and produce cells that take on more specialized functions (1113).
3.5.32.1 Discussion—
The working definition of a stem cell includes self-renewal and the ability to differentiate into several cell types. There are also
aspects of clonality and potency. Stem cells can be derived from early embryos after the formation of the blastocyst or from fetal,
postnatal, or adult sources and can include induced pluripotent stem cells.
3.5.33 syngeneic, adj—from cells, tissues, and organs in which the donor has a genotype unreactive with the recipient. Also known
as syngraft,isograft,isogeneic, or isogenic. (F2311)
3.5.34 synthetic, adj—chemically synthesized. (F2311)
3.5.35 viable cell, n—a cell capable of metabolic activity that is structurally intact with a functioning cell membrane. (F2739)
3.5.36 xenogeneic or xenogenic, adj—from cells, tissues, and organs in which the donor and recipient belong to different species.
Synonyms: xenogenous,heterogeneic, or heterologous. (F2311)
3.6 Medical and Surgical Procedures:
3.6.1 autolysis, n—removal of devitalized tissue using destruction of cells and/or tissues by the body’s own enzymes (1214).
3.6.2 biological debridement, n—therapy using living organisms to digest necrotic tissue and pathogens (1214).
3.6.3 debridement, n—the removal of foreign material and devitalized or contaminated tissue f
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