The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies.

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Wound repair and regeneration: Mechanisms, signaling, and translation

The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have many functions in wounds, including host defence, the promotion and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound and that the influence of these cells on each stage of repair varies with the specific phenotype. Although the macrophage is beneficial to the repair of normally healing wounds, this pleotropic cell type may promote excessive inflammation or fibrosis under certain circumstances. Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of nonhealing and poorly healing wounds. As a result of advances in the understanding of this multifunctional cell, the macrophage continues to be an attractive therapeutic target, both to reduce fibrosis and scarring, and to improve healing of chronic wounds.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/9B0BF84E8A239160D32F2EE8214633D3/S1462399411001943a.pdf/div-class-title-inflammation-and-wound-healing-the-role-of-the-macrophage-div.pdf

Inflammation and wound healing: the role of the macrophage.

Wound healing is a complex, highly regulated process that is critical in maintaining the barrier function of skin. With numerous disease processes, the cascade of events involved in wound healing can be affected, resulting in chronic, non-healing wounds that subject the patient to significant discomfort and distress while draining the medical system of an enormous amount of resources. The healing of a superficial wound requires many factors to work in concert, and wound dressings and treatments have evolved considerably to address possible barriers to wound healing, ranging from infection to hypoxia. Even optimally, wound tissue never reaches its pre-injured strength and multiple aberrant healing states can result in chronic non-healing wounds. This article will review wound healing physiology and discuss current approaches for treating a wound.

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Chronic Wound Healing: A Review of Current Management and Treatments

Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis...

Wound Healing: A Cellular Perspective.

The ability to rapidly restore the integrity of a broken skin barrier is critical and is the ultimate goal of therapies for hard-to-heal-ulcers. Unfortunately effective treatments to enhance healing and reduce scarring are still lacking. A deeper understanding of the physiology of normal repair and of the pathology of delayed healing is a prerequisite for the development of more effective therapeutic interventions. Transition from the inflammatory to the proliferative phase is a key step during healing and accumulating evidence associates a compromised transition with wound healing disorders. Thus, targeting factors that impact this phase transition may offer a rationale for therapeutic development. This review summarizes mechanisms regulating the inflammation-proliferation transition at cellular and molecular levels. We propose that identification of such mechanisms will reveal promising targets for development of more effective therapies.

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Transition from inflammation to proliferation: a critical step during wound healing

In the United States, chronic wounds affect 6.5 million patients. An estimated excess of US$25 billion is spent annually on treatment of chronic wounds and the burden is rapidly growing due to increasing health care costs, an aging population and a sharp rise in the incidence of diabetes and obesity worldwide. The annual wound care products market is projected to reach $15.3 billion by 2010. Chronic wounds are rarely seen in individuals who are otherwise healthy. In fact, chronic wound patients frequently suffer from "highly branded" diseases such as diabetes and obesity. This seems to have overshadowed the significance of wounds per se as a major health problem. For example, NIH's Research Portfolio Online Reporting Tool (RePORT; http://report.nih.gov/), directed at providing access to estimates of funding for various disease conditions does list several rare diseases but does not list wounds. Forty million inpatient surgical procedures were performed in the United States in 2000, followed closely by 31.5 million outpatient surgeries. The need for post-surgical wound care is sharply on the rise. Emergency wound care in an acute setting has major significance not only in a war setting but also in homeland preparedness against natural disasters as well as against terrorism attacks. An additional burden of wound healing is the problem of skin scarring, a $12 billion annual market. The immense economic and social impact of wounds in our society calls for allocation of a higher level of attention and resources to understand biological mechanisms underlying cutaneous wound complications.

Human skin wounds: a major and snowballing threat to public health and the economy.

Objective: To test whether the use of a wireless electroceutical dressing (WED) (Procellera®) in conjunction with a 5-day negative pressure wound therapy (NPWT) may reduce the number of dressing changes required per week with this therapy.

Approach: At the Ohio State University Comprehensive Wound Center, chronic wound patients (n=30) undergoing NPWT were randomized into two arms following consent as approved by the institutional review board. The control arm received standard of care NPWT, where the dressing change was performed thrice a week. The test arm received the same care except that the WED was added as an interface layer and dressing change was limited to twice a week.

Results: A reduced cost of care was achieved using the WED in conjunction with NPWT. Despite fewer dressing changes in wounds dressed with the WED, closure outcomes were comparable with no overt signs of any wound complication, including infection. The cost of NPWT care during the week was significantly lower (from $2918 to $2346) in the WED-treated group compared with patients in the control arm.

Innovation: This work introduces a novel technology platform involving a WED, which may be used in conjunction with NPWT. If used as such, NPWT is effective in decreasing the frequency of dressing change and lowering the cost of care.

Conclusion: This work points toward the benefit of using the WED combined with NPWT. A larger clinical trial investigating the cost-effectiveness of WED in wound care is warranted.

/pdf/a-wireless-electroceutical-dressing-lowers-cost-of-negative-57mtxjrp4s.pdf

A Wireless Electroceutical Dressing Lowers Cost of Negative Pressure Wound Therapy

Chronic non-healing wounds are a major health problem with steadily increasing importance.1 The prevalence of chronic leg ulcers is 3%–5% in the population over 65 years of age, with an increase of up to 12% in the population over 70 years of age.2 The most prevalent forms of chronic wounds are leg ulcers caused by chronic venous insufficiency(CVI)3–6 accounting for 70%-90% of ulcers found on the lower leg,7 followed by diabetic foot ulcers.8 Despite significant advances in knowledge, management of chronic wounds continues to involve frequent visits to wound centers and repeated interventions imposing significant burden on patients and society.3,9,10 Chronic wound ulcers are commonly associated with delayed healing requiring an average of 4-6 months, with a substantial number of patients failing to heal.11,12 The burden of chronic wounds is expected to be increasing in coming years with the increased aging and obesity of the population.2

Obstructive sleep apnea (OSA) is a disorder of intermittent hypoxia13–18 and severe vascular complications including hypertension, coronary disease, and stroke.19,22 OSA is present in 5%-10% of the middle-aged population and probably increasing in incidence due to the increasing obesity and age of the population.23 These are also the risk factors of chronic non-healing wounds.2 Therefore, it is very likely that patients with chronic wounds would have higher prevalence of OSA than the general population. We endeavored to characterize the risk factors for OSA in patients of academic wound center and to determine the actual prevalence of OSA in this population.


BRIEF SUMMARY
Current Knowledge/Study Rationale: Patients with non-healing wounds have high prevalence of cardiovascular disease and significant rate of healing failure. The prevalence of obstructive sleep apnea is unknown in this population.

Study Impact: The study identifies a new population with very high pre-test probability for obstructive sleep apnea. Wound healing in this population may stand to benefit from expedited surveillance and treatment strategies for OSA.

Lynn Lambert

Papers

Human skin wounds: a major and snowballing threat to public health and the economy.

A Wireless Electroceutical Dressing Lowers Cost of Negative Pressure Wound Therapy

Prevalence of obstructive sleep apnea in patients with chronic wounds.