Introduction

When a wound fails to progress through the phases of healing in a timely fashion despite the standard of care wound treatment provided, advanced therapies may be warranted.¹ Wound care often needs a multifaceted approach that involves the treatment of entire patient, not just the wound. Clinicians should obtain a comprehensive medical history of the patient and conduct a thorough skin and wound assessment of the patient. This medical history and assessment will lay the foundation of initial treatment.^2-5

Standard of Care in Wound Healing

Standard of care in wound management is patient centered and based on what is considered standard practice and evidence based.⁶ Some key elements of standard practice include⁷:

• Regular assessment of the patient and wound area
• Management of comorbid factors
• Use of adjunctive therapies as appropriate
• Application of the principles of wound bed preparation

One method of implementing these standard practices entails the use of the TIMERS tool, discussed in the next section.

Standard Wound Care Practice: TIMERS

TIMERS is a comprehensive clinical framework that can help address pathophysiological abnormalities of the wound to correct issues that impact wound healing, such as the presence of biofilm. Estimated to be present in up to 60% of chronic and nonhealing wounds, biofilm is a growing obstacle for wound care professionals.⁹ In relation to biofilm management, clinicians can use the TIMERS framework to evaluate which treatment options will help them reach best outcomes for patients. The TIMERS framework consists of⁸:

• Tissue management: This step entails identification of viable versus nonviable tissue. Debridement method(s) may be used to remove devitalized or compromised tissue.
• Inflammation: The presence of infection can stall wound healing. Biofilm often causes continuous inflammation and must be disrupted and removed for healing to progress.⁹
• Moisture balance: Optimization of the moisture level in the wound bed promotes epithelialization. The appropriate management of exudate, including the selection of wound dressings to optimize the wound environment at various healing stages, is a key consideration in the management of wound moisture levels.¹⁰
• Edge or epithelial advancement: Edge or epithelial advancement involves monitoring the closure of wounds as well as the periwound area for progress or regression. Intervention in a stalled or regressive wound edge may involve resolving epibole (rolled wound edges), addressing periwound skin issues, and other factors.
• Repair or regeneration: Clinicians should analyze the wound matrix for optimal healing and stimulate cellular activity in the wound by using advanced treatment modalities.
• Social factors: In taking a holistic approach to wound care, clinicians should consider and address the patient’s social factors, including availability of support and resources, lifestyle factors, and underlying disorders.

Ongoing reassessment should track wound progress or regression, with subsequent adjustment of the plan of care. The following wound characteristics should be closely monitored for improvement, regression, or lack of progression¹¹:

• Inflammation
• Swelling
• Drainage (volume and type)
• Pain and/or tenderness
• Wound dimensions (surface measurements, depth)
• Granulation tissue
• Necrotic tissue or slough
• Tunneling or undermining
• Periwound skin integrity

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When Wounds Fail to Progress

Failure of a patient’s wound to progress toward healing or worsening of the wound condition over an expected time period may indicate a chronic, nonhealing wound. Factors that may contribute to chronic wounds include but are not limited to¹²:

• Unmanaged extrinsic factors such as pressure or mechanical force or trauma
• Increased bacterial load or presence of a biofilm
• Degraded growth factors, cell surface structures, matrix metalloproteinases (MMPs) that result from excessive proteases
• The presence of senescent or aberrant cells in the wound environment
• Improper wound management, including poorly managed comorbid factors (blood glucose levels, venous insufficiency, etc), inappropriate dressing use, presence of devitalized tissue, poor wound hygiene, etc)
• Patient nonadherence to the treatment plan

Advanced Wound Care Therapies

On reassessment of the wound and healing status, it may be determined that advanced wound care therapies may be appropriate to support wound closure in chronic and nonhealing wounds. Consensus by experts in the field of wound medicine suggest a “step down, step up” approach to chronic and hard-to-heal wounds.¹ The principles of this approach involve a clinical framework that recommends the use of a combination of therapies to support disruption of the biofilm. These therapies include aggressive sharp debridement, disruption of biofilm, topical antiseptics or systemic antibiotics, and supportive therapies (nutritional support, diabetes management, offloading, etc) After 1 to 4 days of initial intervention, “stepping down” treatment to focus on optimizing the wound bed for the next 5 to 7 days promotes best outcomes. This phase of treatment includes continued biofilm disruption and removal of devitalized tissue, maintenance of a moist environment, and the use of antimicrobial dressings as appropriate. In addition, wound care professionals should continuously track and assess the patient’s healing progress and utilize advance wound therapies. Ultimately, these methods facilitate wound closure by supporting cellular activity in the wound.¹Advanced wound therapies include a myriad of options. Some advanced therapies promote wound healing by serving as a protective barrier from infection, encouraging autolytic debridement, and managing bacterial burden. The following are several examples of commonly used advanced wound therapies to support chronic and non-healing wounds:

• Cellular and/or tissue-based products (CTPs): These advanced wound therapeutics may be comprised of viable or non-viable tissues.¹³CTPs may facilitate healing by resolving inflammation in chronic and complex wounds by inducing immunomodulation in the wound bed.¹⁴ CTPs for wound care may include stem cell therapies, skin substitute products, tissue-based therapies (eg autologous blood derivatives, advanced cell therapy), epidermal, dermal, and dermoepidermal substitutes, melanocytes, vessels, and genetic manipulation.
• Bioengineered skin or dermal substitutes: Biosynthetic and cell-based skin replacements include keratinocyte grafts, collagen matrices, cellular matrices, autologous or allogenic composites, and keratinocyte grafts.
• Human fibroblast-derived dermal substitutes: These products are produced by culturing human dermal cells. They are composed of extracellular matrix, fibroblasts, and a bioabsorbable scaffold.¹⁵ A randomized controlled trial that involved a bioengineered skin substitute approved for venous leg ulcers demonstrated activated keratinocytes and restoration of fibroblast function at the wound base, normalizing extracellular matrix production and MMP balance, and support of high wound closure rates in the study cohort.^16-18
• Negative pressure wound therapy (NPWT): NPWT is commonly prescribed to support closure in chronic nonhealing wounds, especially those with high levels of exudate. NPWT draws exudate away from the wound, helps pull the wound edges together, and promotes tissue regeneration.¹⁹
• Hyperbaric oxygen therapy: This adjunctive therapy may be considered for recalcitrant or complicated ulcers. The application of hyperbaric oxygen has demonstrated stimulation of angiogenesis and improvements of fibroblast and leukocyte function and cutaneous microvascular reflexes.¹⁵
• Additional advanced therapy options for chronic nonhealing wounds include but are not limited to electrical stimulation, advanced wound dressings, including those with antimicrobial or antibacterial properties, extracorporeal shockwave therapy, platelet-rich plasma therapy, and protease inhibitors.

Conclusion

To support closure in chronic nonhealing wounds, plan of care reassessment is paramount to meeting the patient—and the wound—where they are in the healing process. When standard of care fails to meet the needs of the wound, taking a clinical approach that involves a combination of therapies along with a “step down, step up” approach is essential to achieving best outcomes. The “step down, step up” approach should aggressively address biofilm and use advanced therapeutics such as skin substitute products, cellular-based therapies, NPWT, or other treatment modalities to promote closure in chronic wounds.

References

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