ASTM F2311-03

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Designation: F 2311 – 03
Standard Guide for
Classification of Therapeutic Skin Substitutes
This standard is issued under the fixed designation F 2311; 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 (e) indicates an editorial change since the last revision or reapproval.
1. Scope Dorland’s
2.1.3.3 full-thickness skin wound, n—a skin wound with the
1.1 Thisguidedefinesterminologyandprovidesasystemof
loss of epidermis, and all of the dermis or at least the depth of
classification for products that can be substituted for human or
dermisthatincludesmostorallsourcesofepidermalcellsfrom
animal skin grafts (or grafts of the dermal or epidermal
epidermal adnexae (glands and follicles).
component tissues of skin) in medical and surgical therapies.
2.1.3.4 partial thickness skin wound, n—a skin wound with
Thisguideisintendedtoinclude(orbeexpandableto)possible
the loss of the epidermis and part of the dermis, but retaining
future tissue engineered skin technology that could provide
a layer of viable dermal tissue that includes the sources of
novel or superior therapeutic properties to those of natural skin
epidermal cells from which the wound can heal spontaneously
grafts.
by epidermal tissue regeneration.
1.2 As much as possible, terminology is based on medical
2.1.3.5 open wound, n—a wound that communicates with
dictionary definitions.
the atmosphere by direct exposure. Dorland’s
1.3 Substitutes for skin grafts are classified by clinical
2.1.3.6 ulcer, n—a local defect, or excavation of the surface
utility only; the classification is independent of the technology
of an organ or tissue, which is produced by the sloughing of
used to make a skin substitute, its components, or whether the
inflammatory necrotic tissue. Dorland’s
sources of components include human or animal tissue or other
2.1.4 Skin Wound Physiology:
biological or non-biological materials.
2.1.4.1 wound inflammation, n—a localized protective re-
1.4 This standard does not purport to address all of the
sponse elicited by injury or destruction of tissues, which serves
safety concerns, if any, associated with its use. It is the
to destroy, dilute, or wall off (sequester) both the injurious
responsibility of the user of this standard to establish appro-
agent and the injured tissue. It is characterized in the acute
priate safety and health practices and determine the applica-
form by the classical signs of pain (dolor), heat (calor) redness
bility of regulatory requirements prior to use.
(rubor), swelling (tumor), and loss of function (functio laesa).
2. Terminology
Histologically,itinvolvesacomplexseriesofevents,including
dilation of arterioles, capillaries, and venules, with increased
2.1 Definitions:
permeability and blood flow; exudation of fluids, including
2.1.1 tissue, n—anaggregationofsimilarlyspecializedcells
plasma proteins; and leukocytic migration into the inflamma-
united in the performance of a particular function.
tory focus. Dorland’s
Dorland’s
2.1.4.2 wound contraction, n—the shrinkage and spontane-
2.1.2 skin, n—the outer integument or covering of the body,
ous closure of open skin wounds. Dorland’s
consisting of the dermis and the epidermis, and resting upon
2.1.4.3 wound contracture, n—a condition of fixed high
the subcutaneous tissues. Dorland’s
resistance to passive stretch of muscle, skin or joints resulting
2.1.3 Skin Lesions:
from fibrosis and scarring of the skin or the tissues supporting
2.1.3.1 lesion, n—any pathological or traumatic discontinu-
the muscles or the joints, or both. (This definition is a
ity of tissue or loss of function of a part. In this guide, “skin
modification of Dorland’s definition of contracture, “a condi-
lesion” is intended to encompass skin wounds and skin ulcers.
tion of fixed high resistance to passive stretch of muscle,
Dorland’s
resulting from fibrosis of the tissues supporting the muscles or
2.1.3.2 wound, n—an injury or damage, usually restricted to
the joints, or disorders of the muscle fibers,” because that
those caused by physical means with disruption of the normal
definition does not address fibrosis and scarring in skin.)
continuity of structures. Called also injury and trauma.
2.1.4.4 granulation tissue, n—the newly formed vascular
tissue normally produced in the healing of wounds of soft
This guide is under the jurisdiction of ASTM Committee F04 on Medical and
tissue and ultimately forming the cicatrix [scar]; it consists of
Surgical Devices and Materials and is the direct responsibility of Subcommittee
small, translucent, red, nodular masses or granulations that
F04.41 on Classification and Terminology for TEMPs.
have a velvety appearance. Dorland’s
Current edition approved Sept. 10, 2003. Published November 2003.
Dorland, WAN, Dorland’s Illustrated Medical Dictionary, 29th Ed., W. B.
Saunders Company, Philadelphia, 2000.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.
F2311–03
2.1.4.5 granulations, n—granulation tissue. 2.1.7.3 graft, n—any tissue or organ for implantation or
2.1.4.6 scar, n—fibrous tissue replacing normal tissues de- transplantation. Dorland’s
stroyed by injury or disease. Stedman’s 2.1.7.4 xenograft, n—a graft of tissue transplanted between
2.1.5 Skin Wound Closure and Healing: animals of different species. Called also heterograft, heterolo-
2.1.5.1 wound closure, n—the provision of an epithelial gous graft and heteroplastic graft. Dorland’s
cover over a wound. It can be accomplished by approximating 2.1.7.5 allograft, n—a graft of tissue between individuals of
wound edges, performing a skin [auto]graft, or allowing the same species but of disparate genotype. Called also
spontaneous healing from the edges. Churchill’s allogeneic graft and homograft. Dorland’s
2.1.5.2 heal, v—to restore wounded parts or to make 2.1.7.6 autograft, n—a graft of tissue derived from another
healthy. Dorland’s site in or on the body of the organism receiving it.
2.1.5.3 healing, n—the restoration of integrity to injured Dorland’s
tissue. Dorland’s 2.1.7.7 full thickness skin autograft, n—a skin [auto]graft
2.1.5.4 Discussion—In the surgical wound closure, an im- consistingoftheepidermisandthefullthicknessofthedermis.
portant distinction is made according to whether the surgeon Dorland’s
expects the healing to be accomplished by granulation tissue. 2.1.7.8 split thickness skin autograft, n—a skin [auto]graft
This distinction is made because in the normal physiology of consisting of the epidermis and a portion of dermis.
wound healing, granulation tissue matures into scar with Dorland’s
wound contracture, which is an undesirable outcome (see
2.1.7.9 epidermal autograft, n—an autograft consisting pri-
4.1.2). Wound closure “by approximating the wound edges or marily of epidermal tissue, including keratinocyte stem cells,
performing a skin autograft” is called “healing by first inten- but with little dermal tissue.
tion,” and wound closure by “allowing spontaneous healing 2.1.7.10 dermal autograft, n—askin[autograft]fromwhich
from the edges” is called “healing by second intention.”
epidermis and subcutaneous fat have been removed; used
healing by first intention, n—healing in which union or instead of fascia in various plastic [surgery] procedures.
restorationofcontinuityoccursdirectlywithoutinterventionof Dorland’s
granulations. Dorland’s 2.1.7.11 engraftment, n—incorporation of grafted tissue
healing by second intention, n—union by closure of a wound
into the body of the host. Dorland’s
with granulations which form from the base and both sides 2.1.7.12 graft take, n—engraftment.
toward the surface of the wound. Dorland’s
2.1.7.13 skin substitute, n—abiomaterial,engineeredtissue,
2.1.5.5 tissue regeneration, n—healing in which lost tissue or combination of biomaterials and cells or tissues that can be
is replaced by proliferation of cells, which reconstruct the
substituted for a skin allograft, a skin autograft, an epidermal
normal architecture. medweb autograft, or a dermal autograft in a clinical procedure.
2.1.5.6 tissue repair, n—healing in which lost tissue is
replaced by a fibrous scar, which is produced from granulation 3. Significance and Use
tissue. medweb
3.1 This guide is intended to provide the foundation of
2.1.6 Therapies for Skin Wounds and Ulcers:
standards for clinical assessment, clinical performance, and
2.1.6.1 maintenance therapy, n—therapy of chronically ill
preclinical assessment of substitutes for skin grafts.
patients that is aimed at keeping the pathology at its present
3.2 This guide is intended to aid accurate claims and
level and preventing exacerbation.
labeling for the clinical utilities of substitutes for skin grafts in
2.1.6.2 skin allograft therapy, n—the treatment of skin
regulatory reviews.
wound or skin ulcer by the temporary topical application of
3.3 In this guide, “replacement” and “substitute” have
skin allograft(s).
different meanings, although they can be used synonymously
2.1.6.3 skin replacement surgery, n—surgery that perma-
in ordinary English. “Replacement” is used only as an adjec-
nently replaces lost skin with healthy skin.
tive in the context of “skin replacement surgery,” which is
2.1.7 Biomaterials and Grafts:
2.1.7.1 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
Note that the United States Public Health Service (USPHS) and the United
States Food and DrugAdministration define “Xenotransplantation” more broadly as
function of the body. Dorland’s
“any procedure that involves the transplantation, implantation, or infusion into a
2.1.7.2 dressing, n—any of various materials utilized for
human recipient of either (a) live cells, tissues, or organs from a nonhuman animal
covering and protecting a wound. Dorland’s
source, or (b) human body fluids, cells, tissues, or organs that have had ex vivo
contact with live nonhuman animal cells, tissues or organs.” Because this guide is
intendedtoclassifyskinsubstitutesbyclinicalequivalency,andnotbycomposition,
the dictionary definition is used, for this guide only. It should be understood that an
Stedman, T. L., Stedman’s Medical Dictionary, 27th Ed., Lippincott Williams allograftorautograftsubstitutemayincludeanimalcomponentswhichcauseittobe
& Wilkins, Philadelphia, 2000. also a xenotransplant by the Food and Drug Administration definition.
4 7
Churchill’s Illustrated Medical Dictionary, Churchill Livingstone, New York, For practical details, see Fang, P., Engrav, L. H., Gibran, N. S., Horani, S.,
1989. Kiriluk,D.B.,Cole,J.K.,Fleckman,P.,Heimbach,D.M.,Gauer,G.J.,Matsumura,
Hiley, P., and Barber, P. C., General Pathology (Pathology Foundation H., Warner, P., “Dermatome steeing for autografts to cover Integrat,” J Burn Care
Course), Chapter 3, Healing and Repair, Department of Pathology, University of Rehabil, 23, 2002, pp. 327-332; and Kagan, R. J., Invited editorial J Burn Care
Birmingham, U.K., http://medweb.bham.ac.uk/http/depts/path/Teaching/foundat/ Rehibil, 23, 2002, pp. 326.
repair/healing.html. “a sheet or band of fibrous tissue such as lies deep to the skin …” (Dorland’s).
F2311–03
defined in 2.1.6.3. “Substitute” is used only as a noun in the close by apposition of the edges) that are not expected to heal
context of “skin substitute,” which is defined in 2.1.7.13. spontaneously with good clinical outcome and in a reasonable
time may be treated by skin replacement surgery.
4. Normal Physiology of Skin Wound Healing
4.2.3 Skin replacement surgery is a two-step procedure:
4.2.3.1 The first step of skin replacement surgery is surgical
4.1 Normal Physiology of Healing by Second Intention of
Full Thickness Skin Wounds: excision of the lesion and any necrotic tissue or microbial
4.1.1 The immediate physiological response to a full thick- contamination, resulting in a clean surgical skin wound.
ness open skin wound includes wound inflammation, edema, 4.2.3.2 The second step in skin replacement surgery is the
and fluid loss. For wounds of large area, there may also be a
application of skin autograft to the clean surgical skin wound.
systemic physiological response characterized by fever, hyper-
(1) The physiological response to skin autograft (full
catabolic metabolism, and an increased vulnerability to infec-
thickness or split-thickness) applied to a clean surgical skin
tion. Such a wound is life threatening.
wound comprises a wound closure immediate physiological
4.1.2 Following the immediate physiological response, tis-
response followed by dermal tissue engraftment and epidermal
sue repair replaces lost dermal tissue by a fibrous scar that is
tissue engraftment. The result is healing by first intention in
produced from granulation tissue.
which the lost skin is permanently replaced by intact healthy
4.1.3 Ifthewoundiscontractedenoughbythedermaltissue
skin, with normal tissue architectures of both dermis and
repair process, the wound is closed by regenerated epidermis
epidermis (without significant scar or contracture).
created by migration and proliferation of epidermal tissue from
(2) Dermal tissue engraftment during skin replacement
the wound margins.
surgery with skin autograft may be differentiated from dermal
4.1.4 Systemic physiology during healing by second inten-
tissue regeneration (“lost tissue is replaced by proliferation of
tion: A full or partial thickness open skin wound that is too
cells”) because autograft replaces the lost tissue without a
large in surface area to be promptly closed by wound contrac-
significant increase in the quantity of dermis.
tion and epidermal migration from the margin may be accom-
4.2.3.3 Whenskinautograftisnotimmediatelyavailablefor
panied by continued life threatening systemic physiological
use in skin replacement surgery, a skin allograft or skin
responses.
xenograft may be applied to the clean surgical skin wound for
4.1.5 In addition to the partial or complete immobilization
temporarywoundclosure.(Notethatskinallografthassuperior
of joints, wound contracture and the formation of scar tissue
temporary wound closure properties to those of skin xe-
can result in chronic fragility of the overlaying epidermal
nograft.)
tissue, discomfort, and unacceptable cosmetic appearance.
(1) The application of skin allograft or skin xenograft to a
4.2 Skin Replacement Surgery:
clean surgical skin wound results in an immediate wound
4.2.1 Definitions:
closure physiological response. However the wound closure is
4.2.1.1 clean surgical skin wo
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