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21 Preparation oftheWound Bed oftheDiabetic Foot Ulcer
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387
41. Wei J, Tian J, Tang C, Fang X, Miao R, Wu H, Wang X, Tong
X.The inuence of different types of diabetes on vascular complications. J Diabetes Res. 2022;2022:3448618.
42. Treves F. Treatment of perforating ulcer of the foot. Lancet.
1884;2:949.
43. Schultz GS, Barillo DJ, Mozingo DW, Chin GA.Wound bed preparation and a brief history of TIME.Int Wound J. 2004;1:19–32.
44. Sibbald RG, Elliott JA, Persaud-Jaimangal R, Goodman L,
Armstrong DG, Harley C, Coelho S, Xi N, Evans R, Mayer DO,
Zhao X, Heil J, Kotru B, Delmore B, LeBlanc K, Ayello EA, Smart
H, Tariq G, Alavi A, Somayaji R. Wound bed preparation 2021.
Adv Skin Wound Care. 2021;34:183–95.
45. Schultz GS, Sibbald RG, Falanga V, Ayello EA, Dowsett C, Harding
K, Romanelli M, Stacey MC, Teot L, Vanscheidt W. Wound bed
preparation: a systematic approach to wound management. Wound
Repair Regen. 2003;11(Suppl 1):S1–S28.
46. Mancini S, Cuomo R, Poggialini M, D’Aniello C, Botta G.Autolytic
debridement and management of bacterial load with an occlusive
hydroactive dressing impregnated with polyhexamethylene biguanide. Acta Biomed. 2018;88:409–13.
47. Woo KY, Keast D, Parsons N, Sibbald RG, Mittmann N.The cost
of wound debridement: a Canadian perspective. Int Wound J.
2015;12:402–7.
48. Patry J, Blanchette V. Enzymatic debridement with collagenase
in wounds and ulcers: a systematic review and meta-analysis. Int
Wound J. 2017;14(6):1055–65.
49. Falcone M, De Angelis B, Pea F, Scalise A, Stefani S, Tasinato R,
Zanetti O, Dalla Paola L.Challenges in the management of chronic
wound infections. J Glob Antimicrob Resist. 2021;26:140–7.
50. Wilson MR, Nigam Y, Knight J, Pritchard DI, Michael Wilson
CR.What is the optimal treatment time for larval therapy? A study
on incubation time and tissue debridement by bagged maggots of
the greenbottle y, Lucilia sericata. Int Wound J. 2019;16:219–25.
51. Pöppel A-K, Vogel H, Wiesner J, Vilcinskas A. Antimicrobial
peptides expressed in medicinal maggots of the blow y Lucilia
sericata show combinatorial activity against bacteria. Antimicrob
Agents Chemother. 2015;59:2508–14.
52. Costela-Ruiz V, Garciá-Recio E, Sherman RA, De Luna-Bertos
E.Advantages of maggot debridement therapy for chronic wounds:
a bibliographic review. Adv Skin Wound Care. 2020;33:515–24.
53. Thomas DC, Tsu CL, Nain RA, Arsat N, Fun SS, Sahid Nik Lah
NA.The role of debridement in wound bed preparation in chronic
wound: a narrative review. Ann Med Surg (Lond). 2021;71:102876.
54. Shimada K, Ojima Y, Ida Y, Matsumura H. Efcacy of Versajet
hydrosurgery system in chronic wounds: a systematic review. Int
Wound J. 2021;18(3):269–78.
55. Michailidis L, Bergin SM, Haines TP, Williams CM.A systematic
review to compare the effect of low-frequency ultrasonic versus nonsurgical sharp debridement on the healing rate of chronic diabetesrelated foot ulcers. Ostomy Wound Manage. 2018;64(9):39–46.
56. Chang YR, Perry J, Cross K. Low-frequency ultrasound debridement in chronic wound healing: a systematic review of current evidence. Plast Surg (Oakv). 2017;25(1):21–6.
57. Kataoka Y, Kunimitsu M, Nakagami G, Koudounas S, Weller CD,
Sanada H. Effectiveness of ultrasonic debridement on reduction
of bacteria and biolm in patients with chronic wounds: a scoping
review. Int Wound J. 2021;18(2):176–86.
58. Ayello EA, Dowsett C, Schultz GS, Sibbald RG, Falanga V, Harding
K, Romanelli M, Stacey M, Teot L, Vanscheidt W.TIME heals all
wounds. Nursing (Lond). 2004;34(4):36–41.
59. Smith F, Dryburgh N, Donaldson J, Mitchell M. Debridement
for surgical wounds (review). Cochrane Database Syst Rev.
2013;(9):CD006214.
60. Lebrun E, Tomic-Canic M, Kirsner RS. The role of surgical
debridement in healing of diabetic foot ulcers. Wound Repair
Regen. 2010;18(5):433–8.
61. Nassiri S, Zakeri I, Weingarten MS, Spiller KL.Relative expression of proinammatory and antiinammatory genes reveals differences between healing and nonhealing human chronic diabetic foot
ulcers. J Invest Dermatol. 2015;135(6):1700–3.
62. Steed DL, Donohoe D, Webster MW, Lindsley L.Effect of extensive
debridement and treatment on the healing of diabetic foot ulcers.
Diabetic ulcer study group. J Am Coll Surg. 1996;183(1):61–4.
63. Brem H, Stojadinovic O, Diegelmann RF, Entero H, Lee B, Pastar
I, etal. Molecular markers in patients with chronic wounds to guide
surgical debridement. Mol Med. 2007;13(9):30–9.
64. Falanga V, Brem H, Ennis WJ, Wolcott R, Gould LJ, Ayello
EA.Maintenance debridement in the treatment of difcult-to-heal
chronic wounds. Recommendations of an expert panel. Ostomy
Wound Manag. 2008;(Suppl:2–13):14–5.
65. Elraiyah T, Domecq JP, Prutsky G, Tsapas A, Nabhan M, Frykberg
RG, et al. A systematic review and meta-analysis of debridement methods for chronic diabetic foot ulcers. J Vasc Surg.
2016;63(2):29S–36S.
66. Wysocki AB. Wound uids and the pathogenesis of chronic
wounds. J WOCN. 1996;23(6):283–90.
67. Armstrong DG.The future of diabetic foot and wound assessment:
stick and rudder visual cues or instrument-rated? Diabet Foot J.
2018;21:1–3.
68. Armstrong DG, Lew EJ, Hurwitz B, Wild T.The quest for tissue
repair’s holy grail: the promise of wound diagnostics or just another
shing expedition? Wound Med. 2015;8:1–5.
69. Serena TE, Hanft J, Synder R. The lack of reliability of clinical examination in the diagnosis of wound infection: analysis
of a venous leg ulcer clinical trial. Int J Low Extrem Wounds.
2008;7:32–5.
70. Le L, Baer M, Briggs P, Bullock N, Cole W, DiMarco D, Hamil
R, Harrell K, Kasper M, Li W, etal. Diagnostic accuracy of pointof- care uorescence imaging for the detection of bacterial burden
in wounds: results from the 350-patient FLAAG trial. Adv Wound
Care. 2021;10(3):123–36.
71. Demidova-rice TN, Geevarghese A, Herman IM. Bioactive peptides derived from vascular endothelial cell extracellular matrices
promote microvascular morphogenesis and wound healing invitro.
Wound Repair Regen. 2011;19(1):59–70.
72. Serena TE, Cullen BM, Bayliff SW, Gibson MC, Carter MJ,
Chen L, Yaakov RA, Samies J, Sabo M, Demarco D, et al.
Dening a new diagnostic assessment parameter for wound
care: elevated protease activity, an indicator of nonhealing, for
targeted protease- modulating treatment. Wound Repair Regen.
2016;24:589–95.
73. Läuchli S, Swanson T, Serena T, Harding K.The use of a point-ofcare test for bacterial protease activity in chronic wounds. Wounds
Int. 2015;6:22–8.
74. Armstrong DG, Bauer K, Bohn G, Carter M, Snyder R, Serena
TE.Principles of best diagnostic practice in tissue repair and wound
healing: an expert consensus. Diagnostics (Basel). 2020;11(1):50.
75. Duteille F. Evaluation of the use of a point of care test for proteases to identify patients with increased risk of skin graft failure. Copenhagen, Denmark: European Wound Management
Association; 2013.
76. Izzo V, Meloni M, Vainieri E, Giurato L, Ruotolo V, Uccioli
L.High matrix metalloprotease levels are associated with dermal
graft failure in diabetic foot ulcers. Int J Low Extrem Wounds.
2014;13:191–6.
77. Fife CE, Carter MJ. Wound care outcomes and associated cost
among patients treated in US outpatient wound centers: data from
the US wound registry. Wounds. 2012;24:10–7.
78. Wu L, Norman G, Dumville JC, Meara OS, Sem B, Wu L, etal.
Dressings for treating foot ulcers in people with diabetes: an
overview of systematic reviews. Cochrane Database Syst Rev.
2015;2015(7):CD010471.
388
https://t.me/med1917
K. Riemer and K. Buczkowski
79. Boulton AJM.Pressure and the diabetic foot: clinical science and
ofoading techniques. Am J Surg. 2004;187(5 Suppl. 1):17–24.
80. Game FL, Apelqvist J, Attinger C, Hartemann A, Hinchliffe RJ,
Löndahl M, Price PE, Jeffcoate WJ.Effectiveness of interventions
to enhance healing of chronic ulcers of the foot in diabetes: a systematic review. Diabetes Metab Res Rev. 2016;32(suppl 1):154–68.
81. Eskes AM, Ubbink DT, Lubbers MJ, Lucas C, Vermeulen
H.Hyperbaric oxygen therapy: solution for difcult to heal acute
wounds? Systematic review. World J Surg. 2011;35(3):535–42.
82. de Smet GHJ, Kroese LF, Menon AG, Jeekel J, van Pelt AWJ,
Kleinrensink GJ, Lange JF. Oxygen therapies and their effects on
wound healing. Wound Repair Regen. 2017;25(4):591–608.
83. Frykberg RG.Topical wound oxygen therapy in the treatment of
chronic diabetic foot ulcers. Medicina (Kaunas). 2021;57(9):917.
84. Zhao DY, Su YN, Li YH, Yu TQ, Li J, Tu CQ.Efcacy and safety
of recombinant human epidermal growth factor for diabetic foot
ulcers: a systematic review and meta-analysis of randomised controlled trials. Int Wound J. 2020;17(4):1062–73.
85. Fang RC, Galiano RD.A review of becaplermin gel in the treatment
of diabetic neuropathic foot ulcers. Biologics. 2008;2(1):1–12.
86. Belvedere R, Novizio N, Morello S, et al. The combination of
mesoglycan and VEGF promotes skin wound repair by enhancing
the activation of endothelial cells and broblasts and their crosstalk. Sci Rep. 2022;12:11041.
87. Lazic T, Falanga V.Bioengineered skin constructs and their use in
wound healing. Plast Reconstr Surg. 2011;127(Suppl):75S–90S.
88. Santema TB, Poyck PP, Ubbink DT.Systematic review and metaanalysis of skin substitutes in the treatment of diabetic foot ulcers:
highlights of a Cochrane systematic review. Wound Repair Regen.
2016;24(4):737–44.
89. Olena P, Prokopyuk V, Figueiredo C, Pogozhykh D. Placenta and
placental derivatives in regenerative therapies: experimental studies, history, and prospects. Stem Cells Int. 2018;2018:1–14.
90. Maxson S, Lopez EA, Yoo D, Danilkovitch-Miagkova A, Leroux
MA. Concise review: role of mesenchymal stem cells in wound
repair. Stem Cells Transl Med. 2012;1:142–9.
91. Gibbons GW. Grax®, a cryopreserved placental membrane,
for the treatment of chronic/stalled wounds. Adv Wound Care.
2015;4:534–44.
92. Tottoli EM, Dorati R, Genta I, Chiesa E, Pisani S, Conti B. Skin
wound healing process and new emerging technologies for skin
wound care and regeneration. Pharmaceutics. 2020;12(8):735.
Topical Wound Care Treatment
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andIndications forTheir Use
AbbyHargis, NargesMaskanBermudez, MaritaYaghi,
andRobertS.Kirsner
22
Abstract
In this chapter, we will explore topical wound care and the
evidence to support their use in diabetic foot ulcer
patients. The chapter is divided into two main sections
that will rst explore dressings and then review topical
growth factors and biologically active products. Various
wound care compounds, dressings, and devices are
discussed.
Introduction
It is generally agreed that diabetic foot ulcers (DFUs)
should initially be treated by management of systemic factors that may impede healing; vascular assessment; assessment for skin, soft tissue, and bone infection; consistent
ofoading; debridement; and maintenance of a moist
wound environment, and if after 4weeks the wound has not
closed by 50%, adjunctive therapies should be added [1].
Sibbald etal. and Falanga rst described the methodology
of preparing the wound bed in 2000, which is a process that
lends itself well to caring for DFU [2, 3]. The TIME principle of wound bed preparation (Tissue, Infection, Moisture
balancing, Edge enhancement) presents a stepwise plan in
addressing different factors that could be limiting the progression and healing of a DFU [4–6]. Of interest, there are
topical wound care agents that address each facet presented
in the TIME principle. As examples, topical debriding
agents, both mechanical and enzymatic, work in part by
direct wound contact and promote a clean tissue bed.
Topical antimicrobial agents such as silver and cadexomer
iodine target infection control. Topical dressings are
designed to optimize and cultivate a moist wound environ-
A. Hargis (*) · N. M. Bermudez · M. Yaghi · R. S. Kirsner
Dr. Phillip Frost Department of Dermatology and Cutaneous
Surgery, University of Miami Miller School of Medicine,
Miami, FL, USA
e-mail: hargisal@evms.edu
ment as well as promote edge enhancement and epithelialization. Despite the use of this principle, in 2015, the
Cochrane review presented an overview of systematic
reviews investigating different dressings for treating DFUs,
which concluded that “there was no clear evidence that any
of the ‘advanced’ wound dressings types was better than
basic wound contact dressings for DFUs. Findings were
limited, however, by the small amount of information available (a limited number of trials involving small numbers of
participants)” [7]. The conclusion was based on 13 systematic reviews that contained 17 relevant randomizedcontrolled trials published up to 2013. There were ten
different types of wound dressings evaluated in a total of 37
different comparisons. However, the outcome measures
differed signicantly between studies and several were
deemed to provide low- quality evidence. A shortcoming of
such studies was a failure to acknowledge that no one dressing type may not be appropriate for all phases of wound
closure. An ideal approach will ultimately be stepwise and
requires combination therapies to achieve wound healing.
In 2022, a meta-analysis was published investigating various dressing types for DFUs. Wang etal. looked into healing
rates of nine dressings in 36 randomized control trials. The
following dressing types were included: “conventional dressing, alginate dressing, chitosan dressing, hyaluronic acid
dressing, platelet-rich plasma dressing, amniotic membrane
dressing, honey dressing, human recombinant growth factor
dressing, and silver ionomer dressing” [8]. In contrast to the
earlier review, this review found that seven dressings, “chitosan dressing, hyaluronic acid dressing, platelet-rich plasma
dressing, amniotic membrane dressing, honey dressing,
human recombinant growth factor dressing, and silver ionic
dressings” were able to achieve higher healing rates than
conventional dressings. Further, among these seven dressings, hyaluronic acid dressings, amniotic membrane dressings, honey dressings, and platelet-rich plasma dressings
have demonstrated “relatively high healing rates and can be
preferred.” However, this study reports limitations affecting
the strength of their evidence, such as the inclusion of only
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
A. Veves et al. (eds.), The Diabetic Foot, Contemporary Diabetes, https://doi.org/10.1007/978-3-031-55715-6_22
389
390
Hydrocolloids,
e
Foam
Least
Absor
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A. Hargis et al.
English and Chinese literatures, some papers were of low
quality, and only healing rate indicators were explored without corresponding cost factors.
Role ofDressings
While high-quality evidence remains scarce on the use of
one topical dressing over another, dressings play a pivotal
role in facilitating the TIME concept for diabetic foot wound
care. Hence, the evaluation and subsequent selection of
dressings in a stepwise fashion ts into routine clinical
practice. Today, there are nearly 200 product manufacturers
marketing hundreds of brands of traditional (woven and nonwoven) and advanced wound dressings [9]. Combined, there
are thousands of wound dressings available on the market.
The Moist Wound Environment andDressings
In 1948, the dermatologist Dr. Gilje published his work on
enhanced wound epithelization with the use of tape. Working
with venous ulcers, he covered the wound with strips of
adhesive tape spaced 3mm apart and noticed that the portion
of the ulcer covered by the tape epithelialized faster. The use
of moisture retentive dressings to cover ulcers in 15/23
(65%) patients led to wound closure in 12 weeks [10].
Shortly after, in the 1960s, George Winter introduced the
concept of an optimal local environment for wound healing,
bringing the importance of dressings to light [11]. His studies compared the rate of epithelialization in a moist versus a
dry wound environment and showed that reepithelialization
occurred twice as fast in a moist environment where a crust
or scab was unable to form. These experiments were subsequently replicated in human subjects by Himman and
Maibach and conrmed Winter’s ndings [12]. These ndings precipitated an evolution in dressings that were increasingly designed to interact with the wound to provide an ideal
environment for repair.
Studies over many years clearly demonstrated that
moisture- retaining dressings that prevent crust formation
allow for faster wound healing, diminish risk of infection,
necessitate less dressing changes, and establish an environment that promotes wound healing [13]. Contrary to early
concerns, the moist environment created by occlusive dressings does not lead to increased infection rates. In fact, a retrospective analysis of the literature found a decrease in the
incidence of wound infection (on both acute and chronic
wounds) with the use of occlusive dressings [14].
There are numerous commercially available wound care
products on the market. These products offer many benets
including the maintenance of a moist wound environment,
the provision of antimicrobial activity, absorbance of excessive exudate, diminishing inammatory cytokines that drive
protease production which may be toxic to the healing process, promoting growth factors integral to wound healing,
and debridement of necrotic and brotic tissue. It is important to note that while wound care dressings may provide all
of these benets, additional treatment in terms of pressure
relief, compression, and antimicrobial therapy may be
needed.
Dressings have been positioned in several product categories, generally based on their structure or composition.
Dressings may also be categorized by absorptive capacity
(Fig.22.1). Dressings commonly used in basic wound care
strategies include hydrogels, hydrobers, amorphous hydrogels, moist gauze, nonwoven sleeve dressings, transparent
lms, hydrocolloids, alginates, hydropolymers, hydroconductives, medicated dressings, impregnated gauze, honey,
foams, collagen or extracellular matrix type, superabsorbents, and combination products. The following section
describes products in the category and our experiences with
their use in diabetic foot ulcers.
Hydrogels are complex, hydrophilic, organic, crosslinked polymers, consisting of a 80–90% water base, primarily available in a free-owing amorphous gel. These
nonadhesive dressings absorb a minimum amount of uid by
swelling and in general are used to keep wounds moist and
Fig. 22.1 Dressing types
arranged from least to most
absorptive
ptive
Film Dressings
Nonwoven Dressings
Gauze
Hydropolymers
Hydrogels
Alginates
Most
Adsorptiv
Hydrofibers
22 Topical Wound Care Treatment andIndications forTheir Use
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391
thermally insulated. Importantly, they promote autolytic
debridement by donating moisture to a dry wound bed. They
have also been shown to promote granulation and epithelialization and reduce the temperature of a wound bed by up to
5 °C [15]. Hydrogels are permeable to gas and water but
have proven to be a less effective bacterial barrier than more
occlusive dressings. Their main application is in hydrating
dry wound beds and softening and loosening slough and
necrotic wound debris. They are unable to absorb heavy
drainage due to their high-water concentration and they
absorb very slowly. Therefore, they are not useful on highly
exudative wounds and they generally require a secondary
dressing. One benet is that they can be used on a variety of
wound types including pressure ulcers, partial- and fullthickness wounds, and vascular ulcers. As they cannot hold a
large amount of exudate, maceration is a concern. Hence,
peri-wound skin areas need to be protected from excess
hydration. Among their benets, hydrogel dressings can be
used in conjunction with topical medications or antibacterial
agents. They are also transparent and allow the direct visualization of wounds. They may remain in place for up to 3days
and required coverage with secondary dressings.
Hydrogel dressings are three-dimensional lattices made
up of a hydrophilic polymer, such as polyvinylpyrrolidone,
and mimic the natural extracellular matrix (ECM) of the skin
in regard to the high-water amount [16]. Studies related to
hydrogels date back to 1990s. One clinical trial comparing
hydrogel to a hydrocolloid evaluated pressure ulcers and
reported a marked benet for the former [17]. A subsequent
study evaluated hydrogel versus povidone-iodine solution in
pressure ulcers and demonstrated superiority for the hydrogel. Conversely, two studies comparing hydrogel dressings
to clostridial collagenase to treat pressure ulcers have shown
superiority for the latter [18]. Their structural properties
make them highly useful for the treatment of burn wounds or
large supercial abrasions, used in conjunction with cell- or
tissue-based products (CTPs) [16]. Additionally, when compared with no coverage for wounds, hydrogels and hydrocolloid dressings have been reported to increase epidermal
healing by approximately 40% [19].
However, large trials investigating hydrogels for the treatment of DFUs remain scarce. A meta-analysis investigating
three studies comparing hydrogel dressings with basic
wound contract dressings found signicantly greater healing
with the use of hydrogels. Findings were consistent across
DFUs of different severities [20]. No large randomizedcontrolled trials comparing hydrogel dressings with other
advanced dressing types have been reported [20]. However,
as DFUs are usually highly exudative, therefore these dressings are not very useful for neuropathic DFU unless the
wound is very shallow and only drains minimally.
Nevertheless, they are useful for excoriation or cracking
caused by dry skin in this patient population. Hydrogel
dressings are also useful in treating painful inammatory
ulcers and other supercial wounds caused by trauma.
Included in this category, though not true hydrogel sheets,
are bio-cellulose wound dressings. They are made from
puried bacterial cellulose, which can both deliver and
absorb moisture. These dressings accelerates autolytic
debridement while providing a protective seal over the
wound similar to a blister roof [21]. They can additionally
deliver silver as well.
Hydrober dressings are made of carboxymethylcellulose (CMC). Once these bers come in contact with serosanguinous exudate from the wound bed, they form a gelatinous
material that aids in autolytic debridement [22]. They rapidly
absorb exudate and have a large absorptive capacity (up to
three times the capacity of alginates) [23]. An additional
advantage over alginates is their mechanism of vertical
uptake of exudate, thereby protecting the peri-wound skin
from maceration. They are highly useful for heavily draining
wounds or when extended wear is required. Hydrobers also
reduce the levels of matrix metalloproteinases (MMP) and
the amount of debris on the wound. In patients with neuropathic ulcers that are being treated with a total contact cast,
hydrober dressings can be kept on for 7days. When they
contain silver, they also play a role in reducing the wound’s
bacterial burden. Hydrober dressings containing silver also
can help to reduce wound odor [24]. Hydrobers have been
evaluated in DFUs and found to be effective in exudate management and the promotion of healing. In combination with
appropriate off-loading, they have been found to reduced
DFU depth, thus reducing the rate of infections requiring
antibiotic treatment [25].
Amorphous hydrogels come packaged in tubes, spray
bottles, or foil packets. Largely composed of a cornstarchderived, polymerized compound that forms a gel upon hydration, they are available commercially in a powdered or
pre-mixed form. They may also be impregnated into gauze.
In the amorphous hydrogel, the hydrophilic polymer has not
been cross-linked and therefore remains in a more aqueous,
gel-like state. As the primary ingredient is water, it can dry
rather quickly if not covered with a semi-occlusive or occlusive dressing. In contrast, amorphous hydrogels donate
moisture. Thus, they can be useful to soften eschar or callus.
As they may dry, their removal requires the use of water.
Several amorphous hydrogels contain additives such as collagen, calcium alginate, or CMC in order to augment absorptive capacity.
Moist gauze has often been used as the control arm in
DFUs’ healing trials. Moist-to-moist gauze dressings and
effective off-loading have been considered standard of care
(SOC) for neuropathic DFUs [26]. The dressing regimen
consists of daily changes with dry gauze as the secondary
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dressing and anchored with an adhesive tape or bulky rolled
gauze bandage. This method is typically employed for
uncomplicated supercial ulcers off-loaded with a healing
sandal and the use of crutches but should be avoided in large
exudative ulcers, if it affects the t of the off-loading device
and avoided with the use of a total contact cast.
Nonwoven dressings, such as sleeve dressings or nonadherent brand dressings, and nonwoven island dressings
with an adhesive border are useful for very supercial minimally draining wounds. It is important to check the safety of
the adhesive for use with diabetic skin to avoid reinjure and
wound formation upon removal.
Foam dressings combine occlusion and moist wound
healing with some degree of absorption. They are semipermeable dressings and are usually between 0.5 and 1 cm
thick. They are foamed bilaminate polyurethane, silicone, or
similar polymers that create open compartments (open cell
foam) with the ability to hold exudate. Their absorptive
capacity is largely dependent on the size and number of open
cells generated during the foaming process. Many foams
also have a thin urethane lm covering their outer surface.
This polymeric lm over the top maintains the moist environment by regulating the moisture vapor transmission rate
(MVTR) and helps provide a seal from water and exogenous
bacteria. Foam dressings may additionally harbor an adhesive coating over the wound contact layer or may have an
island conguration where the foam is at the center and the
perimeter provides the adhesive contact layer. Foam dressings may also contain additives such as surfactants, glycerin,
or superabsorbents aimed at improving the function of the
foam. There are also foam dressings that are impregnated
with antibacterial agents such as silver or poly- hexamethylene
biguanide (PHMB).
Foam dressings are often used as primary dressings.
They are also highly useful secondary dressings when
used with a topical debriding gel, antimicrobial gel, or
topically applied growth factor. Their use is appropriate
for DFUs with moderate to heavy drainage, or for ulcers
with minimal drainage where the dressing can remain in
place up to 3–7days. The concomitant use of a secondary dressing, an adhesive tape, or a bandage is necessary
to keep the dressing in place unless an island dressing
where adhesive covers the perimeter is employed. The
foam design is highly effective at absorbing wound fluid
and keeping it away from the wound. This attribute is
highly desirable in chronic wounds as it has been shown
that chronic wound fluid may be harmful to cells and the
provisional matrix that drives healing. Foam dressings
also provide a cushion that may be helpful to protect the
wound from friction or trauma. They are generally comfortable for the patient and conform to the shape of the
wound, a desirable quality when treating DFUs given
their chronicity. However, their use is not meant for dry
or minimally exudating DFUs as they may have an undesirable drying effect that will hinder the healing process.
Despite these positive characteristics, a meta-analysis of
two studies indicated that foam dressings did not promote the healing of DFUs compared with basic wound
contact dressings [27].
However, overall foams have not been well studied in
DFUs. A meta-analysis found no large trials investigating
foam dressings in DFUs, and the studies included were small
and/or had limited follow-up times [27]. The intrinsic properties of some foams provide signicant advantages. In particular, they provide benets in terms of their ability to
provide a moist wound environment and promote wound
healing, provide mechanical protection, nonadherence to the
wound or to applied cell- and tissue-based products (CTPs),
minimize pain and trauma, absorb excess exudate, and allow
for gaseous exchange as they are semipermeable. They also
are noncytotoxic to healthy tissue and possibly contain antimicrobial activity. They are acceptable to the patient, easy to
use, and cost-effective.
Transparent lm dressings were rst introduced as IV
site dressings or surgical incise drapes. They were commonly used as dressings in the late 1970s and have been
shown to promote the healing of acute partial thickness,
minimally draining, wounds [28]. These thin polyurethane
sheets have no absorptive capacity and therefore not useful
for the treatment of DFUs. Additionally, they are not suitable for infected wounds [29] and therefore not recommended for DFUs [30]. Exudate tends to accumulate,
causing surrounding skin maceration. Despite creating a
barrier from exogenous bacteria, drainage loosens the seal
of the edge allowing exogenous bacteria to gain entry.
However, they are very useful to treat supercial abrasions,
skin tears, and diabetic bullae.
Hydrocolloid dressings are non-permeable, airtight
dressings that do not allow the transport of oxygen or other
gases. In the 1970s, wound healing research with hydrocolloids dispelled the antiquated notion that the wound should
be allowed “to breathe” [31] by demonstrating that atmospheric oxygen delays the healing process and that oxygenation through the blood circulation provides the entirety of
the oxygen necessary for wound repair [32]. On the other
hand, the occlusive nature of hydrocolloids makes them a
questionable dressing for DFUs as does their limited capacity to manage exudate. However, their use is particularly useful when autolytic debridement is desired.
Mixing a hydrocolloid, such as CMC, with gelling agents,
(i.e., gelatin) and combining them with an adhesive elastomer such as isobutylene creates these dressings. Dispersed
discrete particles around which water molecules and solvated ions form a shell-like structure make up hydrocolloid
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dressings. Fluid absorption occurs principally by particle
swelling and enlargement of this structure. Certain hydrocolloid formulations can adhere to wet surfaces because of particle swelling and phase inversion. When placed over a moist
wound bed, contact with the exudate triggers the immediate
dissolution of the contact area, allowing the formation of a
semisolid gel that allows for dressing removal without reinjury. Following exudate absorption, a yellow/light brown
gelatinous mass forms and covers the wound even after
dressing removal and irrigation may facilitate removal. This
is important to know so as not be confused with pus and
therefore wound infection. It is also important to be aware of
the characteristic odor that forms as hydrocolloids and gelatin decompose over the wound. This odor can also be eliminated by cleansing the wound after dressing removal. The
environment created by hydrocolloids is acidic (pH5) and
has been shown to inhibit the growth of pathogens such as P.
aeruginosa and S. aureus.
Alginate dressings are the calcium salts of alginic acid,
a derivative of brown seaweed, that have been spun into a
ber. These bers can be congured into multiple forms
such as compressed nonwoven sheets or bound into ropes.
When wound uid contacts the calcium alginate, a viscous
sodium alginate gel forms as the sodium in the uid replaces
the calcium in the alginate. Alginates are bioerodible and
will gradually dissolve with moisture over time. The greatest advantage of the alginate dressings is their absorptive
capacity, and they are ideal for heavily draining wounds.
Their appropriate use can also decrease the need for frequent dressing changes. The sheet form is ideal for supercial wounds, while the ribbon or cord ones are more suitable
for packing deeper wounds and tracts, including those characterized by infection, tunnels, sinus tracts, or harboring
exposed tendons. If used in wounds with minimal drainage,
bers will dry out and adhere to the wound bed. The concomitant use secondary dressing is therefore important to
keep the gel moist. Alginates have been reported to have
intrinsic hemostatic and bacteriostatic properties [33].
Alginate dressings are also available with the topical antibacterial silver (controlled- release ionic silver). A metaanalysis compared alginate dressings with basic wound
contact dressings, foam dressings, and a silver-containing,
brous-hydrocolloid dressing. Pooled analysis has failed to
show clinical benet in terms of better DFU healing with
the use of alginates [34].
Hydropolymers are foamed gels that wick exudate away
from the wound to the upper layers of the pad. The backing
material has a very high moisture vapor transmission rate
(MVTR) and allows for the evaporation of excess uid.
Hydropolymer dressings are available with silver as well.
These dressings are useful for moderate and heavily draining
wounds or when the dressing needs to remain in place for an
extended period of time. There is some evidence that these
dressings can decrease matrix metalloproteases at the wound
interface. A post-marketing Phase IV trial of 6993 patients
investigating hydropolymers included 9.5% DFUs. It showed
59.0% healing and 36.2% improvement [35].
A hydroconductive dressing absorbing system is formed
by two types of absorbing layers that work together to
allow the movement of large quantities of exudate and bioburden away from the wound bed and through the dressing.
These dressings can withstand up to 50 times their own
weight in uid for up to 7days, without breaking down or
leaving dressing residues on the wound bed. During multiple trials, hydroconductive dressings have been shown to
signicantly reduce the bioburden together with the components required by bacteria to proliferate in the wound.
The wound bed shows a substantial reduction in MMPs,
bacterial counts, including serious bacteria like methicillinresistant Staphylococcus aureus (MRSA). This is accom-
plished by attracting the bacteria and its components from
the wound base into the dressing. A prospective cohort
study demonstrated a signicant decrease in bacterial bioburden in DFUs with the use of hydroconductive dressings.
In one report, signicant decrease in wound size was also
achieved in a midfoot ulcer in a foot with mild Charcot
deformity [36].
Medicated dressings are devices that contain an agent
(usually an antimicrobial) in order to supplement its function. As noted, there has been great interest in the use of
silver- containing dressings. Metallic silver harbors antimicrobial properties that have been used empirically for
thousands of years. Data on its mechanism of action, antiinammatory properties, toxicity, and historical background is widely available [37]. Additionally, silver
appears to decrease the levels of upregulated matrix
metalloproteinases found in nonhealing, chronic wounds.
Various dressings containing silver in a variety of different forms currently exist, such as silver-coated polyethylene membrane, silver- impregnated activated charcoal
cloth, alginates, foams and hydrocolloids containing silver, microcrystalline silver on the adhesive portion of a
transparent lm, silver powders, and even amorphous
hydrogels containing silver. The antimicrobial properties
of several of these silver-containing dressings have been
shown to be effective against bacteria (MRSA), vancomycin-resistant enterococci (VRE)), Pseudomonas aerugi-
nosa, fungi, viruses, and yeast [38]. Antimicrobial
resistance to silver is rare. Interestingly, the silver content
and antimicrobial activity of the various dressings vary
considerably, and most are limited to the supercial
organisms located on the wound bed. A recent systemic
review of 26 randomized-controlled trials did not nd evidence of increased wound healing on uninfected wounds
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with silver [39], and in acute, noninfected wounds, silver
may delay healing. More specic to DFUs, a systematic
review examining the efcacy of silver in healing DFUs
did not nd any randomized-controlled trial comparing
silver dressings to a control and concluded that more trials
are needed to determine their effectiveness [40]. It is
important to know that silver may stain tissues, causing
localized argyria, and they are relatively expensive.
Polyhexamethylene biguanide (PHMB), a chlorhexidine
derivative, has been used as an antimicrobial agent by the
contact lens industry for years. Exceedingly safe, different forms are available, including foam, ribbons, and
gauze. Recently, several manufacturers have incorporated
this antimicrobial agent into their wound dressings, since
PHMB is active against a broad spectrum of bacteria,
fungi, molds, and yeasts. These dressings are comforting
and therefore recommended for painful wounds.
Iodine preparations have been historically criticized
because of their cytotoxicity. However, cadexomer iodine
formulations release iodine in quantities that are not harmful
to cells. Cadexomer iodine is available either in an absorbent
gel or a paste dressing. Cadexomer iodine has been studied
in both venous ulcers [41] and DFUs [42] with favorable
results, but these studies had relatively small sample populations. Caution remains observed in patients with thyroid
disease and iodine sensitivity, pregnant women and breastfeeding women, children, or neonates. No randomizedcontrolled clinical trial investigating the efcacy of
cadexomer iodine for DFUs exists.
Combination products/impregnated gauze dressings are
gauzes and nonwoven dressings that are incorporated with
agents that affect their function. They allow the use of
dressings as drug delivery devices. Saline, oil, zinc salts,
petrolatum, or bismuth tribromophenate bacteriostatic
agents are most commonly used. Gauze or polyethylene
may also be impregnated with salts and inorganic ions that
appear to decrease the harmful effects of MMPs in chronic
wounds. Polyhydrated ionogen impregnated dressings have
shown high efcacy in the treatment of DFUs. Stable
wound epithelization was seen in all full closure patients
(80%) up to the latest follow-up of 1year [43].
Honey has been used to promote wound healing since
ancient times. Its acidic pH, low water content, and hydrogen peroxide secretion drastically decrease the ability of
microorganisms in a wound bed to develop resistance
[44]. Honey is available in a tube or gel form and can be
applied either to gauze or directly to the wound. It is safe
for daily use with dressing changes and has also been
shown to decrease the amount of slough, exudate, and
malodor in the wound bed, in addition to its anti-inammatory and immune-modifying effect. As the wound
secretions lessen, the number of required dressing changes
decreases. A controlled, comparative study between honey
and povidone-iodine for Wagner type II in 30 patients
with DFUs did not nd statistical signicance between
the two groups in healing time [45]. A recent systemic
review found insufcient evidence for the use of honey in
clinical practice for chronic, diabetic wounds [46]. More
research is needed to accurately determine the effectiveness of honey on wound healing.
Gauze has been used as dressings in many clinical trials.
While gauze is inexpensive and conforms well, it also
adheres to wound, does not prevent bacterial translocation,
and only absorbs its own weight in uid. Wet-to-moist (with
0.9% sodium chloride solution) gauze dressing have been
written about extensively, but it is usually practiced as wetto- dry dressings which have been shown to be inferior to
gauze dressing with topical clostridial collagenase in one
diabetic foot study [47]. In addition, others have cited foreign body reactions, repetitive trauma, and wound cooling as
negatives of gauze. Bacterial translocation and increased
infection rates have also been commented on when compared to hydrocolloids and foams [48, 49]. There is no clinical data to support the clinical efcacy of impregnated gauze
in the diabetic foot wound. The nonabsorbent nature of these
dressings in the average DFU patient limits utility of these
dressings for DFU.
Growth Factors andBioengineered Skin
Growth Factors
Growth factors (GFs) are polypeptides that have panoply
of functions in the human body. Through their involvement in cell proliferation, chemotaxis, extracellular
matrix formation, angiogenesis, and wound contraction,
they play fundamental roles in wound healing. Growth
factor therapy offered a promising approach to wound
healing that may work by addressing the deciency in the
chronic wound. However, in clinical practice, utility of
growth factor therapy is limited. There are a few factors
that might contribute to the difculty in assessing the clinical utility of growth factors. First, it is possible that the
delivery system has not been optimized to accommodate
the transient nature of growth factors. Second, the protease-containing wound environment is hostile to proteins,
and the growth factor peptides may be broken down before
the intended therapeutic effect has time to occur. Third,
resident cells in chronic wounds have undergone a phenotypic change rendering them less responsive to GFs. There
is evidence that broblasts from chronic wounds, including DFUs, are not able to respond to certain growth fac-
Percentage of Wounds Closed
Percentage of Office Visits Where Debridement Was Performed
01
60
Percentage of Wounds Closed
Number of Weeks
ease in
22 Topical Wound Care Treatment andIndications forTheir Use
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Fig. 22.2 Sharp debridement
is important to successful
growth factor therapy
REGRANEX Gel 0.003% Placebo Gel
50
64
50
395
83
53
20
10
0
010203040506070809
Fig. 22.3 Seminal rhPDGF
trial results
50
40
30
20
10
0
246810 12
REGRANEX Gel 0.01% n=123
Placebo Gel n=123
6-Week decrease in healing time
tors [50, 51]. Therefore, repeated debridement of tissue
from around the wound in order to remove these unresponsive cells is thought to allow peptides to function as
they should, as has been advocated for in the setting of
PDGF in DFUs ([52], Fig.22.2).
The Cochrane review recently identied 28 growth factor
trials looking at 2365 patients with neurologic, vascular, or
combined DFUs conducted in ten countries. The trials
assessed 11 growth factors in 30 different comparisons.
Growth factor compounds reviewed included plateletderived wound healing formula, autologous growth factor,
allogenic platelet-derived growth factor, transforming growth
factor b2, arginine-glycine-aspartic acid peptide matrix,
recombinant human platelet-derived growth factor (becaplermin), recombinant human epidermal growth factor, recombinant human basic broblast growth factor, recombinant
human lactoferrin, and recombinant human acidic broblast
growth factor. This review demonstrated that any growth factor (657 patients) compared with placebo or no growth factor
(482) increased complete wound healing, (345) 53% versus
(167) 35%. However, while based on 12 trials, the data was
driven by trials of platelet-derived wound healing formula
36/56 (64.28%) versus 7/27 (25.92%) and by trials of recombinant human platelet-derived growth factor (becaplermin)
36
17
32
17
50
50
14 16 18 20
90
00
43%
incr
wound
closure
205/428 (48%) versus 109/335 (33%). Interestingly, there
was no clear evidence of difference between any growth factor and placebo, or no growth factor on its effect of decreasing on amputation [53].
To date, the only GF approved by the FDA for DFU is
becaplermin (rhPDGF-BB). Four prospective, randomized, double-blinded studies of rhPDGF-BB were performed on neuropathic DFUs (Fig.22.3). Patients were
treated with rhPDGF-BB at a dose of 2.2mg/cm2, CMC,
or vehicle alone for 20weeks or until complete wound
closure occurred. Results from this study demonstrated
that 48% healed following treatment with rhPDGF-BB
[54], while only 25% healed with vehicle alone (p<0.01).
The median reduction in wound area was 98.8% for
rhPDG-BB-treated patients, but only 82.1% for those
treated with vehicle. There were no significant difference
in the incidence or severity of adverse events in either
group (Fig.22.4). In a phase III, randomized, placebocontrolled, double-blinded study investigating topical
rhPDGF in neuropathic DFUs, results supported the benefits of this treatment. Following 20weeks, becaplermin
gel 100 mg/g led to wound closure in 50% of patients
versus 35% in patients treated with placebo gel
(p = 0.007). Additionally, time to wound closure was
396
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Ulcers Healed (%)
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Fig. 22.4 rhPDGF-BB path
to FDA approval
100
90
80
70
60
50
40
30
20
10
P – 02
48%
25%
0
Study 1
1-118
improved in the treatment arm, 86 versus 127 days
(p=0.013). The safety of becaplermin gel was found to
be similar to that of placebo [55].
Although the FDA released a black box warning in 2008
for the use of becaplermin as a result of evidence of increased
mortality from malignancy when using three or more tubes,
this warning was lifted in 2019, in part because typically
treatment with DFUs usually require less than two tubes
(1.7 tubes) [56].
In addition to topically applied GF therapy, GF may be
delivered by gene therapy. There are three different concepts in gene therapy for chronic wounds: (1) synthesis of
human recombinant growth by gene therapy techniques, (2)
exvivo transfection of cell cultures (broblasts, keratinocytes) with growth factor DNA and subsequent transplantation of transfected cells on chronic wounds, and (3) invivo
transfection with growth factor DNA, e.g., gene gun, liposomes, and viral vector. Currently, most gene therapy trials
have been targeted at ischemic foot ulcers in diabetics, usually with freedom from amputation as an endpoint, as
opposed to wound closure.
A Phase III study of VM202 (ENGENSIS), a plasmid
DNA expressing two isoforms of human hepatocyte growth
factor (HGF), was discontinued in 2019 due to a slow enrollment rate. However, 44 patients had completed the study at
the time of discontinuation, and interim results were presented in 2021 as well as on the clinical trials’ governmental
Placebo Gel
Becaplermin 0.003%
Becaplermin Gel 0.01%
P – 01
NS
32%
Study 4
1-250
36%
36%
35%
1278132
Study 2
1-328
50%
22%
12368
NS
36%
70
Study 3
44%
34 122128
website. This study tested the effect of injections into the calf
muscle of patients with DFUs and concomitant peripheral
arterial disease (PAD) without evidence of osteomyelitis or
involvement of bone, tendon, or capsule. In this population,
there was a “positive trend toward wound closure” from
month 3 to month 7. Interim results suggest HGF gene therapy may have promise for neuroishemic DFUs; however,
larger studies are needed to conrm [57].
Bioengineered Skin
Bioengineered skin (BES) is a novel therapy in use over the
last few decades in chronic wounds. BES in clinical use to
date does not itself survive long in the wound site; however,
the placement of the product on the wound stimulates a shift
in wound healing trajectory via restoration of the matrix and
delivery of growth factors [58, 59]. Three bioengineered skin
products have been approved for use in DFU. These are
BLCC (Apligraf), DSS (Dermagraft), and IDRT (Omnigraft).
BLCC and DSS are cellular-based matrix products that
deliver broblasts and in the case of BLCC keratinocytes as
well, cultured in various matrices. IDRT is a bilayer dermal
matrix acting as a barrier and scaffold. These advanced
tissue- based products have demonstrated improved wound
healing over standard of care (SOC). A comparison of
evidence- based products, including cell-, tissue-, and growth
factor-based therapies for the treatment of DFUs is summarized in Table22.1.
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