Association of Tryptophan: Kynurenine Metabolites with Healing in Chronic Venous Leg Ulcers.

OBJECTIVE: Chronic wound healing is a complex process that is still not well understood. The tryptophan (TRP)-L-Kynurenine (KYN) pathway has recently been under increased scrutiny in regards to wound healing. The study applied metabolomics to elucidate the TRP-L- KYN pathway associated with wound healing in chronic venous leg ulcers (CVLUs). APPROACH: This study used a longitudinal comparative design of 60 serum samples collected from 30 older adult patients with CVLUs, receiving weekly sharp debridement at a wound clinic. The serum samples were collected at baseline and week 4 (healed wounds) or week 8 (non-healed wounds). Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to analyze targeted metabolites. A Bayesian approach was employed to examine robust correlations between changes in metabolite values and linear healing slope and to compare by group. RESULTS: The mean age was 71.13 (±9.46). Half of the sample were female and the minority (17%) were Black. The mean values of evaluated metabolites for the non-healed group were consistently lower than those for the healed group. The healed group (n=12) had higher KYN values; Those on a healing trajectory (n=23) had lower KYN levels and higher TRP levels at baseline and over time. There was moderate support (Bayes Factor = 3.70) for a negative association between change in Kynurenic Acid and linear healing slope (r = -0.35, CrI = -0.62, -0.04, PD= 98%). Results suggest KYN and TRP may be markers for healing in individuals with CVLUs. INNOVATION AND CONCLUSION: Gaining a better understanding of the associations between the TRP-L- KYN pathway and the healing of CVLUs may help to clarify the links of inflammation with the rate and success of wound healing. Biomarker development focused on the TRP-L- KYN pathway could be pursued, if the associations are further supported by focused research studies.

Associations Among Wound-Related Factors Including Biofilm, Wound-Related Symptoms and Systemic Inflammation in Older Adults with Chronic Venous Leg Ulcers.

Objective: The purposes of this observational prospective study were to (1) characterize the wound-related factors (wound area, the presence of biofilm, and total bacteria), wound-related symptoms (fatigue, pain, exudate, itching, and edema or swelling), and systemic inflammation (level of serum C-reactive protein [CRP]), and (2) explore associations between wound-related factors, wound-related symptoms, and systemic inflammation in older individuals with chronic venous leg ulcers (CVLUs) over 8 weeks of wound treatment. Approach: A total of 117 participants who received standardized care (weekly sharp debridement) for chronic venous ulcer were enrolled. We collected clinical data every 2 weeks during the 8 weeks of the study period or until the wound was healed (if healed before 8 weeks). Associations among variables were estimated using a Bayesian approach applied to general linear mixed models. Results: Based on Bayes factor (BF) value, there was extremely strong evidence for the association of biofilm with mean total bacteria (BF >1,000). There was moderate evidence of a direct association between biofilm presence and levels of CRP (BF 4.3) and moderate evidence of direct associations between biofilm and wound-related symptoms, pain and exudate (BF 5.12, 8.49, respectively). Innovation: Wound-related symptoms and the level of systemic CRP were associated with biofilm among patients who were receiving weekly sharp debridement. Symptom severity associated with CVLUs requires assessment and management of wound-related factors and levels of inflammation in addition to symptom assessment. Conclusion: This study is the first to examine associations among biofilm, as wound-related factors, systemic inflammation, wound-related symptoms, and wound healing in clinical settings. Symptom severity, level of systemic CRP, and wound-related factors should be considered as well as assessment of biofilm in CVLU in older individuals with CVLU.

Sleep, Fatigue, and Inflammatory Biomarkers in Older Adults with Chronic Venous Leg Ulcers Receiving Intensive Outpatient Wound Care.

Objective: Chronic venous ulcers are a relatively common and distressing condition that disproportionately affects older individuals. Along with multiple concomitant issues such as wound drainage, pain, and mobility impairments, individuals with chronic venous leg ulcers (CVLUs) commonly report sleep disturbances and fatigue; however, limited research has examined these symptoms in relation to inflammatory biomarkers in this population over the intensive wound care treatment trajectory. This study aimed at describing the symptoms of sleep and fatigue in older adults with CVLUs receiving intensive wound treatment with weekly debridement and exploring the relationships between these symptoms and tumor necrosis factor-alpha (TNF-α), c-reactive protein (CRP), and interleukin (IL)-6. Approach: Demographics, clinical characteristics, Pittsburgh Sleep Quality Index (PSQI) scores, Brief Fatigue Inventory (BFI), TNF-α, CRP, and IL-6 levels were collected from 84 older adults with CVLUs at three time points (baseline, week 4, and week 8). Data analysis included descriptive statistics and Bayesian estimation of associations. Results: Findings showed a consistent pattern of poor sleep quality and mild fatigue among these individuals. Lower IL-6 levels at week 4 and higher CRP levels at week 8 were linked to poor sleep quality. Higher CRP levels were linked to greater fatigue at baseline and week 8. Sleep and fatigue were correlated at all time points. Innovation and Conclusion: This study highlights the importance of clinicians evaluating sleep and fatigue in those with CVLUs. Further research is needed to validate circulating inflammatory biomarkers to enhance our understanding of sleep and fatigue's role in wound healing.

Biomarkers of sleep disturbance in adults with chronic illness: A scoping review.

OBJECTIVES: The purpose of this scoping review was to identify which biomarkers for sleep disturbance were the most prevalent and significant in the literature across chronic illnesses. METHODS: A scoping review was conducted, following Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, to provide a map of the existing literature on the biomarkers of sleep disturbance in adults with chronic illness. Peer-reviewed articles published between 2010-2020 were included if they measured a biomarker and discussed sleep deprivation, disturbance, or dysfunction secondary to a chronic illness. RESULTS: A total of 21 articles were included and synthesized using data charting. There were 24 different biomarkers identified, most commonly collected through serum. Biomarkers were grouped, then biomarkers and correlations with sleep were identified and mapped. DISCUSSION: Overall, the most common biomarkers studied were interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), c-reactive protein (CRP), and interleukin-1 beta (IL-1ß). Cytokines were the most commonly studied biomarkers, with a majority of studies focusing on pro-inflammatory cytokines. Based on the results of this review, CRP, IL-6, TNF-α, and erythrocyte sedimentation rate (ESR) showed themost significant correlations with sleep across all chronic illnesses. Future research is still needed to identify an ideal biomarker for sleep disturbance that can be used across chronic illnesses.

The association of wound factors and symptoms of fatigue and pain with wound healing in chronic venous leg ulcers.

The purpose of this study was: (1) to characterise the association of wound area, wound exudate C-reactive protein (CRP), broad-spectrum matrix metalloprotease protein (MMPs), and symptoms of fatigue and pain in individuals with chronic venous leg ulcers (CVLUs) over time and (2) to identify factors associated with the wound healing trajectory in CVLUs. Seventy four participants with CVLU who received weekly sharp debridement were recruited from a wound care clinic during the 8-week study period. To examine associations among wound CRP, MMPs, pain, fatigue, and wound healing trajectory over time, we calculated Bayes factors (BF) based on a linear mixed model. The mean age of participants was 71.8 (SD = 9.8) and the mean wound area was 2278 mm2 (SD = 7085 mm2 ) at baseline. Higher fatigue was strongly associated with higher MMPs (BF = 9, 95% HDI: [-.05, .43]), lower CRP (BF = 11, 95% HDI: [-.02, .002]), and large areas of wound (BF = 20, 95% HDI: [-.001, .01]). Higher CRP and MMPs activity in wound exudate and higher fatigue were associated with a larger wound area. To facilitate wound healing, clinicians need to utilise the multifactorial approach, which includes wound treatment and management of symptoms such as pain and fatigue, because of the molecular and psycho-behavioural factors involved in wound healing.

Multidimensional Pain Characteristics in Older Adults with Chronic Venous Leg Ulcers.

Objective: Pain affects wound healing, treatment, and quality of life because it has significant impacts on physical, psychological, and social well-being. Despite the fact that more than half of chronic venous leg ulcer (CVLU) patients experience mild-to-moderate pain, the multidimensional characteristics of CVLU pain are not well documented. The objective of this study was to describe the multidimensional pain characteristics, including the sensory, affective, cognitive, and behavioral dimensions, of CVLU before debridement. Approach: Participants (N = 40) were recruited from a wound clinic. We conducted a descriptive analysis of clinical data, including pain, wound, and demographic characteristics, collected at the first visit. Results: The mean age of participants was 70.8 ± 9.1 years, 22 (55%) participants were female, and 35 (87.5%) were white. Participants reported mean current pain intensity (2.9 ± 2.7), least (1.2 ± 2.2) and worst (4.8 ± 3.4) pain intensity in 24 h, and tolerable pain level (4.9 ± 2.64) on a 0-10 scale. They described pain as periodic (66.7%, n = 26) with multiple pain quality descriptors (5.4 ± 2.9). Their past pain treatments provided some pain relief (65%, n = 25). For 68% (n = 27), their pain was the same as they expected. Nearly all had a tendency not to tell others about their pain (95%, n = 38). Innovation: This study is the first to describe the multidimensional pain characteristics of patients with CVLU as measured with PAINReportIt. Conclusion: Patients with CVLU reported willingness to tolerate a relatively high level of pain and experience the level of pain they anticipate. Multidimensional pain assessment will assist clinicians to select individualized therapies to manage pain and improve quality of life for these patients.

Metabolomics: Impact of Comorbidities and Inflammation on Sickness Behaviors for Individuals with Chronic Wounds.

Significance: Approximately 6.5 million people in the United States suffer from chronic wounds. The chronic wound population is typically older and is characterized by a number of comorbidities associated with inflammation. In addition to experiencing wound-related pain, individuals with chronic wounds commonly experience multiple concurrent psychoneurological symptoms such as fatigue and depression, which delay wound healing. However, these distressing symptoms have been relatively overlooked in this population, although their adverse effects on morbidity are well established in other chronic disease populations. Recent Advances: Inflammation is involved in multiple pathways, which activate brain endothelial and innate immune cells that release proinflammatory cytokines, which produce multiple symptoms known as sickness behaviors. Inflammation-based activation of the kynurenine (KYN) pathway and its metabolites is a mechanism associated with chronic illnesses. Critical Issues: Although putative humoral and neuronal routes have been identified, the specific metabolic variations involved in sickness behaviors in chronic wound patients remain unclear. To improve health outcomes in the chronic wound population, clinicians need to have better understanding of the mechanisms underlying sickness behaviors to provide appropriate treatments. Future Directions: This article presents a synthesis of studies investigating associations between inflammation, metabolic pathways, and sickness behaviors in multiple chronic diseases. The presentation of a theoretical framework proposes a mechanism underlying sickness behaviors in the chronic wound population. By mediating the immune system response, dysregulated metabolites in the KYN pathway may play an important role in sickness behaviors in chronic inflammatory conditions. This framework may guide researchers in developing new treatments to reduce the disease burden in the chronic wound population.

Optimizing Nutrition Care for Pressure Injuries in Hospitalized Patients.

Significance: It is estimated that up to 50% of hospitalized patients are malnourished. Malnutrition can lead to longer hospital stays, altered immune function, and impaired skin integrity and wound healing. Malnutrition has been found to be a significant factor influencing pressure injury (PI) risk and wound healing. While PI prevention requires multidimensional complex care using a variety of evidence-based strategies, hospitalized patients benefit from interventions that focus on improving oral nutrition to reduce PI risk and enhance wound healing. Unfortunately, malnutrition is often under-recognized and inadequately managed in hospitalized patients and this can lead to higher rates of complications such as PI. Recent Advances: Recent studies suggest that nutritional care has a major impact in PI prevention and management. Strategies, including early identification and management of malnutrition and provision of specially-formulated oral nutritional interventions to at-risk patients, optimization of electronic health record systems to allow for enhanced administration, monitoring, and evaluation of nutritional therapies, and implementation of protocol-based computerized decision support systems, have been reported to improve outcomes. Critical Issues: Unfortunately, there are gaps in the implementation of nutritional care in hospitals. Timely identification and management of malnutrition is needed to advance quality care for hospitalized patients and reduce malnutrition and associated PI. Future Directions: Further research on effective, evidence-based strategies for implementation of all stages of the nutrition care process is needed to reduce pressure injuries and malnutrition in hospitalized patients.

Biobehavioral Mechanisms Associated With Nonhealing Wounds and Psychoneurologic Symptoms (Pain, Cognitive Dysfunction, Fatigue, Depression, and Anxiety) in Older Individuals With Chronic Venous Leg Ulcers.

The prevalence and incidence of chronic venous leg ulcers (CVLUs) are increasing worldwide, as are the associated financial costs. Although it has long been known that their underlying etiology is venous insufficiency, the molecular aspects of healing versus nonhealing, as well as the psychoneurologic symptoms (PNS; pain, cognitive dysfunction, fatigue, depression, and anxiety) associated with CVLUs remain understudied. In this biobehaviorally focused review, we aim to elucidate the complex mechanisms that link the biological and molecular aspects of CLVUs with their PNS. Innovations in "omics" research have increased our understanding of important wound microenvironmental factors (e.g., inflammation, microbial pathogenic biofilm, epigenetic processes) that may adversely alter the wound bed's molecular milieu so that microbes evade immune detection. Although these molecular factors are not singularly responsible for wound healing, they are major components of wound development, nonhealing, and PNS that, until now, have not been amenable to systematic study, especially over time. Further, this review explores our current understanding of the molecular mechanisms by which the immune activation that contributes to the development and persistence of CVLUs also leads to the development, persistence, and severity of wound-related PNS. We also make recommendations for future research that will expand the field of biobehavioral wound science. Biobehavioral research that focuses on the interrelated mechanisms of PNS will lead to symptom-management interventions that improve quality of life for the population burdened by CVLUs.

Demographics, Psychological Distress, and Pain From Pressure Injury.

BACKGROUND: There is a knowledge gap regarding factors that influence the intensity of pain associated with pressure injuries. OBJECTIVES: We examined the influence of age, gender, race, and comorbidity on the relationships between pressure injuries, psychological distress, and pain intensity in hospitalized adults. METHODS: This study was a cross-sectional, retrospective secondary analysis using data from a regional acute hospital's electronic health records from 2013 to 2016. A sample of 454 cases met the inclusion criteria and were analyzed using path analysis. RESULTS: The hypothesized model (Model A) and two alternative models (Models B and C) were tested and demonstrated adequate model fit. All tested models demonstrated statistically significant independent direct effects of age on the severity of pressure injury (p < .001) and pain intensity (p = .001), as well as independent direct effects of gender (p ≤ .005), race (p < .001), and comorbidity (p = .001) on psychological distress. DISCUSSION: Pain management for individuals with pressure injuries should include not only the treatment of wounds but also the individual characteristics of the patient such as demographics, comorbidity, and psychological status that may affect pain. Given the limitations of secondary analyses, further studies are suggested to validate these findings.

Pressure Ulcer Prevalence by Level of Paralysis in Patients With Spinal Cord Injury in Long-term Care.

OBJECTIVE: Scientific literature suggests pressure ulcer (PU) risk increases as immobility increases, indicating that more extensive paralysis confers a greater risk of PU. Yet the specific level of paralysis (ie, hemiplegia vs paraplegia vs quadriplegia), apart from neurodegenerative diagnoses, has never been examined in the long-term care (LTC) population. This study examined the prevalence of PU among LTC residents with different paralysis levels. METHODS: The authors conducted a secondary data analysis of the 2012 US Minimum Data Set of LTC facilities (n = 51,664 residents). Measures included PU stage, level of paralysis, functional impairments, comorbidities, and sociodemographic factors. After removing residents with neurodegenerative disease, comatose patients, and those with hip fractures from the analysis, logistic regressions were used to examine the association of risk factors and sociodemographic characteristics with the presence of PU. MAIN RESULTS: The sample included 7,540 patients with quadriplegia, 11,614 patients with paraplegia, and 32,510 patients with hemiplegia in LTC facilities. The PU prevalence in the sample (stages 2, 3, and 4; suspected deep-tissue injury; and unstageable PUs) was 33.9% for patients with quadriplegia, 47.4% for patients with paraplegia, and 9.6% for patients with hemiplegia. CONCLUSIONS: Within paralysis groups (quadriplegic, paraplegic, hemiplegic), risk factors for PU differed in type and magnitude. The PU rates associated with quadriplegia and paraplegia are much higher than LTC residents without paralysis, and PU prevalence for hemiplegia is similar to the rate in LTC residents without paralysis. When the risk factor of paraplegia versus quadriplegia was isolated, PU prevalence for patients with paraplegia was significantly higher.

Building a Biopsychosocial Conceptual Framework to Explore Pressure Ulcer Pain for Hospitalized Patients.

Although pressure ulcers are a prevalent condition, pain associated with pressure ulcers is not fully understood. Indeed, previous studies do not shed light on the association between pressure ulcer stages and the experience of pain. Especially, pain characteristics of suspected deep tissue injury, which is a new category that was recently added by the National Pressure Ulcer Advisory Panel, are yet unknown. This is concerning because the incidence of pressure ulcers in hospitalized patients has increased exponentially over the last two decades, and health care providers are struggling to ensure providing adequate care. Thus, in order to facilitate the development of effective interventions, this paper presents a conceptual framework to explore pressure ulcer pain in hospitalized patients. The concepts were derived from a biopsychosocial model of pain, and the relationships among each concept were identified through a literature review. Major propositions are presented based on the proposed conceptual framework, which integrates previous research on pressure ulcer pain, to ultimately improve understanding of pain in hospitalized patients with pressure ulcers.

Risk Factors for Pressure Ulcers Including Suspected Deep Tissue Injury in Nursing Home Facility Residents: Analysis of National Minimum Data Set 3.0.

PURPOSE: To provide information on risk factors associated with pressure ulcers (PrUs), including suspected deep tissue injury (sDTI), in nursing home residents in the United States. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Examine the literature related to risk factors for the development of PrUs.2. Compare risk factors associated with the prevalence of PrUs and sDTI from the revised Minimum Data Set 3.0 2012 using a modified Defloor's conceptual model of PrUs as a theoretical framework. OBJECTIVE: This study aims to characterize and compare risk factors associated with pressure ulcers (PrUs), including suspected deep tissue injury (sDTI), in nursing home (NH) residents in the United States. DESIGN: Secondary analysis of the 2012 Minimum Data Set (MDS 3.0). SETTING: Medicare- or Medicaid-certified NHs in the United States. PARTICIPANTS: Nursing home residents (n = 2,936,146) 18 years or older with complete PrU data, who received comprehensive assessments from January to December 2012. MEASUREMENTS: Pressure ulcer by stage was the outcome variable. Explanatory variables (age, gender, race and ethnicity, body mass index, skin integrity, system failure, disease, infection, mobility, and cognition) from the MDS 3.0 were aligned with the 4 elements of Defloor's conceptual model: compressive forces, shearing forces, tissue tolerance for pressure, and tissue tolerance for oxygen. RESULTS: Of 2,936,146 NH residents who had complete data for PrU, 89.9% had no PrU; 8.4% had a Stage 2, 3, or 4 or unstagable PrU; and 1.7% had an sDTI. The MDS variables corresponding to the 4 elements of Defloor's model were significantly predictive of both PrU and sDTI. Black residents had the highest risk of any-stage PrU, and Hispanic residents had the highest risk of sDTI. Skin integrity, system failure, infection, and disease risk factors had larger effect sizes for sDTI than for other PrU stages. CONCLUSIONS: The MDS data support Defloor's model and inform clinicians, educators, researchers, and policymakers on risk factors associated with PrUs and sDTI in NH residents in the United States participating in Medicare and Medicaid.

How Well Does the Braden Nutrition Subscale Agree With the VA Nutrition Classification Scheme Related to Pressure Ulcer Risk?

The VA Nutrition Classification Scheme documented by dietitians was found to be superior in assessing nutritional risk and predicting the development of pressure ulcers in acutely ill hospitalized veterans compared with use of the Braden nutrition subscale.

Bodily pain intensity in nursing home residents with pressure ulcers: analysis of national minimum data set 3.0.

Clinical reports suggest that superficial pressure ulcers produce pain, but that pain decreases as the wound advances in stage. This study of the relationship between pressure ulcer stage and bodily pain intensity in nursing home residents was a secondary analysis of the national Minimum Data Set 3.0 assessment data in long-term care facilities, collected from nursing home residents at least 65 years of age. Data were examined from residents with pressure ulcers who completed a bodily pain intensity interview between January and March 2012 (N = 41,680) as part of the MDS comprehensive assessment. After adjusting for other variables (e.g., cognition, functional impairment, presence of comorbidities, use of scheduled pain medication, and sociodemographic variables), bodily pain intensity for those with more severe pressure ulcers in comparison to those with Stage I ulcers was higher by 11% (Stage II), 14% (Stage III), 24% (Stage IV), and 22% (suspected deep tissue injury). Because multivariate analysis showed that greater bodily pain intensity was associated with an advanced stage of pressure ulcer, health care providers should assess bodily pain intensity and order appropriate pain management for nursing home residents with pressure ulcers, particularly for those with advanced pressure ulcers who are vulnerable to greater bodily pain intensity.

Pressure ulcer-related pain in nursing home residents with cognitive impairment.

PURPOSE: To enhance the learner's competence by providing research about pressure ulcer-related pain in nursing home residents with cognitive impairment. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Explain this study's methodology and tools.2. Predict levels of pressure ulcer pain in a nursing home population with dementia. ABSTRACT OBJECTIVE: The objective of this study was to examine how pain is reported in cognitively impaired nursing home residents with pressure ulcers using the Minimum Data Set 2.0 data set. The study design was cross-sectional, comparative stratified by 3 levels of cognitive impairment and 4 stages of PrUs. PARTICIPANTS: There were 56,577 participants in the study.

Enhancing Braden pressure ulcer risk assessment in acutely ill adult veterans.

This study sought to determine if a parsimonious pressure ulcer (PU) predictive model could be identified specific to acute care to enhance the current PU risk assessment tool (Braden Scale) utilized within veteran facilities. Factors investigated include: diagnosis of gangrene, anemia, diabetes, malnutrition, osteomyelitis, pneumonia/pneumonitis, septicemia, candidiasis, bacterial skin infection, device/implant/graft complications, urinary tract infection, paralysis, senility, respiratory failure, acute renal failure, cerebrovascular accident, or congestive heart failure during hospitalization; patient's age, race, smoking status, history of previous PU, surgery, hours in surgery; length of hospitalization, and intensive care unit days. Retrospective chart review and logistic regression analyses were used to examine Braden scores and other risk factors in 213 acutely ill veterans in North Florida with (n = 100) and without (n = 113) incident PU from January-July 2008. Findings indicate four medical factors (malnutrition, pneumonia/pneumonitis, candidiasis, and surgery) have stronger predictive value (sensitivity 83%, specificity 72%, area under receiver operating characteristic [ROC] curve 0.82) for predicting PUs in acutely ill veterans than Braden Scale total scores alone (sensitivity 65%, specificity 70%, area under ROC curve 0.70). In addition, accounting for four medical factors plus two Braden subscores (activity and friction) demonstrates better overall model performance (sensitivity 80%, specificity 76%, area under ROC curve 0.88).

Understanding the role of nutrition and wound healing.

Optimal wound healing requires adequate nutrition. Nutrition deficiencies impede the normal processes that allow progression through stages of wound healing. Malnutrition has also been related to decreased wound tensile strength and increased infection rates. Malnourished patients can develop pressure ulcers, infections, and delayed wound healing that result in chronic nonhealing wounds. Chronic wounds are a significant cause of morbidity and mortality for many patients and therefore constitute a serious clinical concern. Because most patients with chronic skin ulcers suffer micronutrient status alterations and malnutrition to some degree, current nutrition therapies are aimed at correcting nutrition deficiencies responsible for delayed wound healing. This review provides current information on nutrition management for simple acute wounds and complex nonhealing wounds and offers some insights into innovative future treatments.

The role of doxycycline as a matrix metalloproteinase inhibitor for the treatment of chronic wounds.

Many chronic wounds fail to heal with conventional therapy, resulting in disability and impaired quality of life. New technologies using recombinant growth factors, autologous growth factors, or bioengineered skin-tissue substitutes have been shown to be effective, but these treatments are costly. An effective, low-cost treatment to improve healing of chronic wounds is needed. The molecular environment of chronic wounds, like many other chronic inflammatory diseases, contains abnormally high levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-1beta]) and matrix metalloproteinases (MMPs), which impair normal wound healing. In animal models and clinical studies of ulcerative diseases, doxycycline, an inexpensive and Food and Drug Administration (FDA)-approved antibiotic, appears to inhibit members of the MMP superfamily like MMPs and TNF-alpha-converting enzyme (TACE). This article provides an overview of the roles of MMPs and intrinsic tissue inhibitors of metalloproteinases (TIMPs) in wound healing and the damaging effects of chronically elevated levels of MMPSs in chronic wounds. It also explores the use of topical doxycycline, a synthetic MMP inhibitor (MMPI), to enhance healing of chronic wounds.