Many other factors can impede the ability of wounds to heal. In 2002, a wound consensus group developed the TIME guidelines for the treatment of chronic wounds. The components of this mnemonic are tissue, infection, moisture balance, and edge advancement (Table 1).2 Ensuring that the wound bed has been appropriately prepared is the foundation for wound management. The wound should be clean, free of infection, and have a base of healthy granulation tissue to optimize wound healing. Regular debridement allows for devitalized and necrotic tissue that impairs healing to be removed. This debridement can be performed using surgical, mechanical, autolytic, enzymatic, or biologic techniques. A culture of the wound should be obtained if a wound exhibits clinical signs that are consistent with infection such as erythema extending from the wound, malodor, or purulent drainage. Empiric antibiotic therapy should be initiated and can later be tailored to the culture sensitivities. Cleansing agents and topical antimicrobials also can be used in wound care for local infections.2

 Table 1. TIME Guidelines for Chronic Wound Management2

TissueRemoval of necrotic, devitalized tissue, and slough
InfectionPrevention and treatment of wound infection
Moisture balanceEnsuring an appropriate moisture balance of the wound bed is obtained and excess exudate is  eliminate
Edge advancementProvision of an optimal environment that promotes wound healing at the cellular level
Source: Powers et al.

Moisture is essential when treating chronic wounds as adequate moisture balance promotes keratinocyte migration and wound healing. As such, a wound dressing should be chosen that will allow the wound to achieve this balance without becoming too wet or too dry. There are 5 basic categories of dressings: films, foams, hydrocolloids, alginates, and hydrogels. The amount of exudate from a wound can aid in determining the most appropriate wound dressing. Heavily exudative wounds benefit from alginate dressings that provide more absorptive properties while hydrocolloid or foam dressing is more appropriate for mild to moderately draining wounds. Hydrogels should be considered for wounds that are dry and necrotic, and films are readily used for split-thickness skin grafts.2 Negative pressure therapy, also referred to as vacuum-assisted closure, is also used in wound care to promote an appropriate moisture balance, although this treatment is primarily reserved for wounds with significant depth such as traumatic wounds and surgical wounds.5

Advancement of wound edges is essential for wound healing and is oftentimes multifactorial, requiring local and systemic factors. Biologic skin substitutes can be considered as a treatment modality to promote wound healing. Epidermal, dermal, and dermal-epidermal combination constructs are the 3 main categories of biologic skin substitutes that are used in wound healing.2 These substitutes mimic the architecture of normal skin and promote healing cascades within the wound.

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Hyperbaric Oxygen Therapy and Chronic Wounds 

Hyperbaric oxygen therapy is an additional treatment modality that has proven to aid in obtaining edge advancement in nonhealing wounds.10 This is a noninvasive procedure with few side effects and contraindications that has been used for the treatment of chronic wounds for more than 2 decades.11 In this treatment modality, a patient is placed in an oxygen chamber, called a dive, and administered 100% oxygen at a pressure of 2.0 to 2.5 atmospheres absolute (ATA). This oxygen is infused into the blood, plasma, and cerebral fluids to cause a state of hyperoxia, which promotes wound healing through an increase in growth factors and production of nitric oxide. This results in a release of endothelial progenitor cells that promote the formation of new blood vessels at the wound site and encourage wound closure.2

Hyperbaric chambers have been approved by the US Food and Drug Administration (FDA) for the treatment of crush injuries, gas gangrene, skin graft flap at risk for tissue death, progressive necrotizing infections, chronic refractory osteomyelitis, soft-tissue radionecrosis, and nonhealing diabetic foot ulcers among other diseases.10 According to clinical guidelines, hyperbaric oxygen therapy is indicated for diabetic foot ulcer that have failed an adequate course of standard wound therapy and are classified as a Wagner grade III (Table 2) or higher (indicating the presence of a deep wound with either an abscess formation, joint sepsis, osteomyelitis, or gangrene).10-12

Table 2. Wagner Ulcer Classification System12

0No ulcer is present but patient is at high risk for ulceration
IUlcer is present but superficial. Wound may be partial thickness or full thickness.
IIUlcer extends deep to involve structures such as ligaments, tendons, joint capsule, or deep fascia. No abscess or osteomyelitis is present.
IIIUlcer demonstrates an abscess formation, osteomyelitis, or joint sepsis
IVLocalized gangrene to part of the heel or forefoot
VExtensive gangrene affects the entire foot

When considering hyperbaric oxygen therapy as a treatment modality for chronic wound management, the risks and contraindications should be reviewed with the patient. It is recommended that patients with emphysema have a chest radiograph performed prior to treatment to assess for emphysematous blebs. These blebs may predispose patients to pulmonary barotrauma by air being trapped when there is a change in environmental pressure such as that experienced within the hyperbaric oxygen chamber. There is a 1 in 10,000 chance of a patient having a seizure while undergoing therapy because of oxygen toxicity. If this occurs, the air pressure is lowered to resolve the seizure. As such, patients who are being treated for seizures are at an increased risk for having a seizure during treatment. Patients may also experience a slight change in vision because of increased pressure in the eyes, as well as ear and sinus pain. Claustrophobia is a common concern for people who do not like being in an enclosed oxygen chamber, although sedatives can aid in allowing them to proceed with treatment. The side effects affiliated with hyperbaric oxygen therapy are typically dose-dependent; thus, the greater the atmospheric pressure, the greater the risk for complications.11

The number of treatments needed depends on the individual case and rate of recovery. Treatments are typically given once a day 5 days a week; however, some patients may receive treatments twice daily. The average treatment lasts from 1 to 2 hours.3 Most insurance providers will at least partly cover the cost of hyperbaric oxygen therapy for FDA-approved diseases. Patients with Medicare Part B will have 80% of their hyperbaric oxygen therapy treatments covered although some provisions must be met such as receiving therapy in a single-person oxygen chamber. Although this treatment often results in out-of-pocket costs, patients have previously been able to appeal claims and win coverage when submitting proof of efficacy with this treatment modality.11


As hyperbaric oxygen therapy continues to be utilized as a treatment modality for the healing of chronic wounds, providers should also understand the risks and benefits affiliated with its use and discuss these with their patients so that an informed decision regarding their care can be made. Research suggests that optimal clinical outcomes and quality of life can be obtained with use of hyperbaric oxygen therapy in applicable candidates while also reducing the burden of health care expenditures on the treatment of chronic wounds.

Blakley Sproles, DMSc, MPAM, PA-C, currently practices at the Centra Medical Group Wound Care and Hyperbaric Medicine office in Lynchburg, Virginia; Thomas Colletti, DHSc, PA-C, DFAAPA, is a professor at the University of Lynchburg School of PA Medicine; Michael R. Cook, MD, FAAFP, is medical director of the Centra Wound Care and Hyperbaric Medicine Center and chief operations officer of the Centra Heart and Vascular Institute; David G. Cox, DPM, is a podiatrist at OrthoVirginia in Lynchburg; and Jenna Rolfs, DMSc, MPAS, PA-C, is program director at the University of Lynchburg School of PA Medicine in Lynchburg, VA, and serves as the secretary on the board of directors for the Virginia Academy of PAs.


1. Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care (New Rochelle). 2015;4(9):560-582. doi:10.1089/wound.2015.0635

2. Powers JG, Higham C, Broussard K, Phillips TJ. Wound healing and treating wounds: chronic wound care and management. J Am Acad Dermatol. 2016;74(4):607-625. doi:10.1016/j.jaad.2015.08.070

3. Johnston BR, Ha AY, Brea B, Liu PY. The mechanism of hyperbaric oxygen therapy in the treatment of chronic wounds and diabetic foot ulcers. R I Med J (2013). 2016;99(2):26-29.

4. Armstrong DG, Swerdlow MA, Armstrong AA, Conte MS, Padula WV, Bus SA. Five year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer. J Foot Ankle Res. 2020;13(1):16. doi:10.1186/s13047-020-00383-2

5. Jones RE, Foster DS, Longaker MT. Management of chronic wounds—2018. JAMA. 2018;320(14):1481-1482. doi:10.1001/jama.2018.12426

6. Krzyszczyk P, Schloss R, Palmer A, Berthiaume F. The role of macrophages in acute and chronic wound healing and interventions to promote pro-wound healing phenotypes. Front Physiol. 2018;9:419. doi:10.3389/fphys.2018.0041

7. Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219-29. doi:10.1177/0022034509359125

8. Herberger K, Müller K, Protz K, Zyriax BC, Augustin M, Hagenström K. Nutritional status and quality of nutrition in chronic wound patients. Int Wound J. 2020;17(5):1246-1254. doi:10.1111/iwj.13378

9. Russell L. The importance of patients’ nutritional status in wound healing. Br J Nurs. 2001;10(6 Suppl):S42, S44-49. doi:10.12968/bjon.2001.10.Sup1.5336

10. Mathieu D, Marroni A, Kot J. Tenth European Consensus Conference on Hyperbaric Medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving Hyperb Med. 2017;47(1):24-32. doi:10.28920/dhm47.1.24-32

11. Maxfield WS, Gould J. The Oxygen Cure: A Complete Guide to Hyperbaric Oxygen Therapy. Humanix Books; 2017:1-124.

12. Frykberg RG. Diabetic foot ulcers: pathogenesis and management. Am Fam Physician. 2002;66(9):1655-1662.