Literature review on the management of diabetic foot ulcer

Table 1 Different kind of debridement for patients with diabetic foot ulcer

Method	Explanation	Advantages	Disadvantages
Surgical or Sharp	Callus and all nonviable soft tissues and bone remove from the open wound with a scalpel, tissue nippers, curettes, and curved scissors. Excision of necrotic tissues should extend as deeply and proximally as necessary until healthy, bleeding soft tissues and bone are encountered[59]	Only requires sterile scissors or a scalpel, so is cost-effective[55]	Requires a certain amount of skill to prevent enlarging the wound[55]
Mechanical	This method includes wet to dry dressings, high pressure irrigation, pulsed lavage and hydrotherapy[76], and commonly used to clean wounds prior to surgical or sharp debridement[76]	Allows removal of hardened necrosis	It is not discriminating and may remove granulating tissue It may be painful for the patients[55]
Autolytic	This method occurs naturally in a healthy, moist wound environment when arterial perfusion and venous drainage are maintained[18]	It’s cost-effective[55] It is suitable for an extremely painful wound[18]	It’s time consuming and may require an equivocal time for treatment[18]
Enzymatic	The only formulation available in the United Kingdom contains Streptokinase and Streptodornase (Varidase Topical® Wyeth Laboratories). This enzyme aggressively digests the proteins fibrin, collagen and elastin, which are commonly found in the necrotic exudate of a wound[77,78]	They can be applied directly into the necrotic area[55]	Streptokinase can be systemically absorbed and is therefore contraindicated in patients at risk of an MI It’s expensive[55]
Biological	Sterile maggots of the green bottle fly (Lucilia sericata) are placed directly into the affected area and held in place by a close net dressing. The larvae have a ferocious appetite for necrotic material while actively avoiding newly formed healthy tissue[79,80]	They discriminate between the necrotic and the granulating tissue[79]	There may be a reluctance to use this treatment by patients and clinicians It’s expensive[79,80]

Table 2 Common offloading techniques

Technique	Casting techniques	Footwear related techniques	Surgical offloading techniques	Other techniques
Examples	TCC (Figure 3)	Shoes or half shoes (Figure 7)	ATL	Bed rest
	iTCC (Figure 5)	Sandals	Liquid silicone injections/tissue augmentation	Crutches/Canes/Wheelchairs
	RCW (Figure 4)	Insoles	Callus debridement	Bracing (patella tendon bearing, ankle-foot orthoses)
	Scotch-cast boots (Figure 6)	In-shoe orthoses	Metatarsal head resection osteotomy/arthroplasty/os ectomy/ exostectomy	Walkers
	Windowed casts	Socks	External fixation	Offloading dressings
	Custom splints			Felted foam/padding
				Plugs

Data adapted from Armstrong et al[82]. TCC: Total contact cast; iTCC: Instant TCC; RCW: Removable cast walkers; ATL: Achilles tendon lengthening.

Table 3 Classification of advanced wound dressings used for diabetic foot ulcers healing

Type	Example	Explanation	Advantages	Disadvantages
Hydrocolloids	Duoderm (Convatec) Granuflex (Convatec) Comfeel (Coloplast)	These kind of dressings usually composed of a hydrocolloid matrix bonded onto a vapor permeable film or foam backing. When in contact with the wound surface this matrix forms a gel to provide a moist environment[102]	Absorbent Can be left for several days Aid autolysis[96]	Concerns about use for infected wounds May cause maceration Unpleasant odor[96]
Hydrogels	Aquaform (Maersk Medical) Intrasite Gel (Smith and Nephew) Aquaflo (Covidien)	These dressings consist of cross-linked insoluable polymers (i.e., starch or carboxymethylcellulose) and up to 96% water. These dressings are designed to absorb wound exudate or rehydrate a wound depending on the wound moisture levels. They are supplied in either flat sheets, an amorphous hydrogel or as beads[96]	Absorbent Donate liquid Aid autolysis[96]	Concerns about use for infected wounds May cause maceration using for highly exudative wounds[96]
Foams	Allevyn (Smith and Nephew) Cavicare (Smith and Nephew) Biatain (Coloplast) Tegaderm (3M)	These dressings normally contain hydrophilic polyurethane foam and are designed to absorb wound exudate and maintain a moist wound surface[103]	Highly absorbent and protective Manipulate easily[96] Can be left up to seven days Thermal insulation[96]	Occasional dermatitis with adhesive[96] Bulky[6] May macerate surrounding skin[6]
Films	Tegaderm (3M) Opsite (Smith and Nephew)	Film dressings often form part of the construction of other dressings such as hydrocolloids, foams, hydrogel sheets and composite dressings, which are made up of several materials with the film being used as the outer layer[107,108]	Cheap Manipulate easily Permeable to water vapor and oxygen but not to water microorganisms[95]	May need wetting before removal[96] Aren’t suitable for infected wounds[107,108] Nonabsorbent If fluid collects under film it must be drained or the film replaced[6]
Alginates	Calcium Alginate Dressing (Smith and Nephew Inc., Australia) Kaltostat (ConvaTec) Sorbalgon (Hartman United States, Inc.l) Medihoney (Derma Sciences Inc., Canada)	The alginate forms a gel when in contact with the wound surface which can be lifted off with dressing removal or rinsed away with sterile saline. Bonding to a secondary viscose pad increases absorbency[104]	Highly absorbent Bacteriostatic Hemostatic Useful in cavities[96]	May need wetting before removal[96]
Silver-impregnated	Acticoat (Smith and Nephew) Urgosorb Silver (Urgo)	These dressing used to treat infected wounds as silver ions are thought to have antimicrobial properties[109]	Antiseptic Absorbent[96] Reduce odor Improved pain-related symptoms Decrease wound exudates Have a prolonged dressing wear time[112]	High cost[96]

Table 4 Different types of nonvascular diabetic foot surgery

Type	Explanation
Elective	The main goal of this surgery is to relieve the pain associated with particular deformities such as hammertoes, bunions, and bone spurs in patients without peripheral sensory neuropathy and at low risk for ulceration
Prophylactic	These procedures are indicated to prevent ulceration from occurring or recurring in patients with neuropathy, including those with a past history of ulceration (but without active ulceration)
Curative	These procedures are performed to effect healing of a non-healing ulcer or a chronically recurring ulcer when offloading and standard wound care techniques are not effective. These include multiple surgical procedures aimed at removing areas of chronically increased peak pressure as well as procedures for resecting infected bone or joints as an alternative to partial foot amputation
Emergent	These procedures are performed to arrest or limit progression of acute infection

Data adapted from Frykberg et al[18].

Table 5 Brief description of commonly used bioengineered tissue products

Type	Explanation	Use	RCT studies
Apligraf (Advanced Biohealing Inc., La Jolla, CA)	A bilayered living-skin construct containing an outer layer of live allogeneic human keratinocytes and a second layer of live allogeneic fibroblasts on type 1 collagen dispersed in a dermal layer matrix. Both cell layers are grown from infant fore skin and looks and feels like human skin[164,165]	It’s used for full-thickness neuropathic DFU of greater than 3 wk duration, resistant to standard therapy (also without tendon, muscle, capsule, or bone exposure) and is contraindicated in infected ulcers[167]	Veves et al[168] Falanga et al[169] Edmonds[170] Steinberg et al[171]
Dermagraft (Organogenesis Inc, Canton, Mass)	An allogeneic living-dermis equivalent and includes neonatal fibroblasts from human fore skin cultured on a polyglactin scaffold[164,165]	It’s used for DFU of greater than 6 wk duration, full thickness in depth but without tendon, muscle, joint, or bone exposure and is contraindicated in infected ulcers[164,167]	Marston et al[172] Gentzkow et al[173]
Oasis (Cook Biotech, West Lafayette, IN)	An acellular biomaterial derived from porcine small intestine submucosa, contains numerous crucial dermal components including collagen, glycosaminoglycans (hyaluronic acid), proteoglycans, fibronectin, and bioactive growth factors such as fibroblast growth factor-2, transforming growth factor β1, and VEGF[164,165]	It’s used for full-thickness DFU[174]	Niezgoda et al[174]

DFU: Diabetic foot ulcer; VEGF: Vascular endothelial growth factor.