Surgical Aspects of Wound Care in Older Adults.

The physical, emotional, and financial toll of acute and chronic nonhealing wounds on older adults and their caregivers is immense. Surgical treatment of wounds in older adults can facilitate healing but must consider the medical complexity of the patient, the patient's desires for treatment and the likelihood of healing. Innovative approaches and devices can promote rapid healing. By using a team approach, from preoperative planning to postoperative care, with a focus on the needs and desires of the patient, successful outcomes with improved patient satisfaction are possible even in medically complex patients.

WHS guidelines for the treatment of pressure ulcers-2023 update.

The major populations at risk for developing pressure ulcers are older adults who have multiple risk factors that increase their vulnerability, people who are critically ill and those with spinal cord injury/disease. The reported prevalence of pressure ulcers in the United States is 2.5 million. However, this estimate is derived from acute care facilities and does not include people who are living at home or in nursing facilities. Despite the implementation of hospital and facility-based preventive measures, the incidence of pressure ulcers has not decreased in decades. In addition to the burden of pain, infection and death, it is estimated that hospital-acquired pressure ulcers cost the health system $26.8 billion annually with over 50% of the cost attributed to treating Stage 3 and 4 pressure injuries. Thus, it is critical to examine the literature and develop guidelines that will improve the outcomes of this complex and costly condition. This guideline update is a compendium of the best available evidence for the treatment of Pressure Ulcers published since the last update in 2015 and includes a new section based on changing demographics entitled 'Palliative wound care for seriously ill patients with pressure ulcers'. The overall goal of the Wound Healing Society Guideline project is to present clear, concise and commercial free guidelines that clinicians can use to guide care, that researchers can use to develop studies that will improve treatment and that both clinicians and researchers can use to understand the gaps in our knowledge base.

A core domain set for pyoderma gangrenosum trial outcomes: an international eDelphi and consensus study from the UPGRADE initiative.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with no current standardized outcomes or outcome measures. With a rich investigational therapeutic pipeline, standardization of outcomes and improvement of data quality and interpretability will promote the appropriate and consistent evaluation of potential new therapies. Core outcome sets (COS) are agreed, standardized sets of outcomes that represent the minimum that should be measured and reported in all clinical trials of a specific condition. OBJECTIVES: To identify and reach a consensus on which domains (what to be measured) should be included in the Understanding Pyoderma Gangrenosum: Review and Analysis of Disease Effects (UPGRADE) core domain set for clinical trials in PG. METHODS: Collaborative discussions between patients and PG experts, and a systematic review of the literature identified items and prospective domains. A three-round international eDelphi exercise was performed to prioritize the domains and refine the provisional items (consensus: ≥ 70% of participants rating a domain as 'extremely important' and < 15% of participants voting 'not important'), followed by an international meeting to reach consensus on the core domain set (consensus: < 30% disagreement). Item-generation discussions and consensus meetings were hosted via online videoconferences. The eDelphi exercise and consensus voting were performed using Qualtrics survey software. Participants were adults with PG, healthcare professionals, researchers and industry representatives. RESULTS: Collaborative discussions and systematic reviews yielded 115 items, which were distilled into 15 prospective domains. The eDelphi exercise removed the three lowest-priority domains ('laboratory tests', 'treatment costs' and 'disease impact on family') and ranked 'pain', 'quality of life' and 'physical symptoms' as the highest-priority prospective domains. Consensus was reached on the domains of 'pain', 'quality of life' and 'clinical signs'. The domain of 'disease course/disease progression' narrowly failed to reach consensus for inclusion in the core set (32% of participants voted 'no'). Refinement of this domain definition will be required and presented for consideration at future consensus meetings. CONCLUSIONS: The UPGRADE core domain set for clinical trials in PG has been agreed by international multistakeholder consensus. Future work will develop and/or select outcome measurement instruments for these domains to establish a COS.

Eligibility Criteria for Active Ulcerative Pyoderma Gangrenosum in Clinical Trials: A Delphi Consensus on Behalf of the UPGRADE (Understanding Pyoderma Gangrenosum: Review and Assessment of Disease Effects) Group.

At present, there are no standardized guidelines for determining patient eligibility for pyoderma gangrenosum (PG) clinical trials. Thus, we aim to determine which clinical features, histopathological features, or laboratory features should be included in active ulcerative PG clinical trial eligibility criteria for treatment-naïve patients and patients already treated with immunomodulating medications (treatment-exposed patients). This study employed 4 rounds of the Delphi technique. Electronic surveys were administered to 21 international board-certified dermatologists and plastic surgeon PG experts (June 2022-December 2022). Our results demonstrated that for a patient to be eligible for a PG trial, they must meet the following criteria: (i) presence of ulcer(s) with erythematous/violaceous undermining wound borders, (ii) presence of a painful or tender ulcer, (iii) history/presence of rapidly progressing disease, (iv) exclusion of infection and other causes of cutaneous ulceration, (v) biopsy for H&E staining, and (vi) a presence/history of pathergy. These criteria vary in importance for treatment-naïve versus treatment-exposed patients. Given the international cohort, we were unable to facilitate live discussions between rounds. This Delphi consensus study provides a set of specific, standardized eligibility criteria for PG clinical trials, thus addressing one of the main issues hampering progress toward Food and Drug Administration approval of medications for PG.

Chronic Wound Healing Models.

In this paper, we review and analyze the commonly available wound healing models reported in the literature and discuss their advantages and issues, considering their relevance and translational potential to humans. Our analysis includes different in vitro and in silico as well as in vivo models and experimental techniques. We further explore the new technologies in the study of wound healing to provide an all encompassing review of the most efficient ways to proceed with wound healing experiments. We revealed that there is not one model of wound healing that is superior and can give translatable results to human research. Rather, there are many different models that have specific uses for studying certain processes or stages of wound healing. Our analysis suggests that when performing an experiment to assess stages of wound healing or different therapies to enhance healing, one must consider not only the species that will be used but also the type of model and how this can best replicate the physiology or pathophysiology in humans.

Surgical Reconstruction of Stage 3 and 4 Pressure Injuries: A Literature Review and Proposed Algorithm from an Interprofessional Working Group.

OBJECTIVE: Stage 3 and 4 pressure injuries (PIs) present an enormous societal burden with no clearly defined interventions for surgical reconstruction. The authors sought to assess, via literature review and a reflection/evaluation of their own clinical practice experience (where applicable), the current limitations to the surgical intervention of stage 3 or 4 PIs and propose an algorithm for surgical reconstruction. METHODS: An interprofessional working group convened to review and assess the scientific literature and propose an algorithm for clinical practice. Data compiled from the literature and a comparison of institutional management were used to develop an algorithm for the surgical reconstruction of stage 3 and 4 PIs with adjunctive use of negative-pressure wound therapy and bioscaffolds. RESULTS: Surgical reconstruction of PI has relatively high complication rates. The use of negative-pressure wound therapy as adjunctive therapy is beneficial and widespread, leading to reduced dressing change frequency. The evidence for the use of bioscaffolds both in standard wound care and as an adjunct to surgical reconstruction of PI is limited. The proposed algorithm aims to reduce complications typically seen with this patient cohort and improve patient outcomes from surgical intervention. CONCLUSIONS: The working group has proposed a surgical algorithm for stage 3 and 4 PI reconstruction. The algorithm will be validated and refined through additional clinical research.

The "Understanding Pyoderma Gangrenosum, Review and Assessment of Disease Effects (UPGRADE)" Project: a protocol for the development of the core outcome domain set for trials in pyoderma gangrenosum.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that affects approximately 0.3-6 out of every 100,000 people worldwide. Clinical trials are scarce but there is growing interest in using newer and more targeted therapeutics to achieve disease remission. However, there are no standardized instruments to measure outcomes in PG and, therefore, future clinical trials are hampered by the absence of established and accurate means of assessment and comparison. Therefore, we aim to produce an internationally accepted core outcome set (COS) that will overcome this obstacle. This protocol outlines our intended approach to achieve the first part of this process, establishing a core outcome domain set. METHODS: An international team of PG stakeholders, consisting of physicians, wound care nurses, patients, scientists and industry representatives, has been assembled for the purpose of building a comprehensive and universally established set of core outcome domains. During the first step, we will generate items of relevance using a nominal process from all stakeholders. Items will be distilled and collapsed into potential domains and subdomains. A systematic review of current methods for reporting PG has already been published and domains identified in this work will be considered in the generation of the core domains set. During the second step, after the potential domains and subdomains are identified, stakeholders will participate in an e-Delphi exercise to rate the importance of (sub)domains. A final consensus meeting will be organized with the goal of establishing a core domain set. CONCLUSION: Pyoderma gangrenosum lacks an established COS and previously published clinical trials have used inconsistent measures established from similarly inconsistent domains. As a first step this study seeks to create a core domain set within the COS, to build the foundation for future core outcome work for PG.

Chronic wounds: Treatment consensus.

The Wound Healing Foundation (WHF) recognised a need for an unbiased consensus on the best treatment of chronic wounds. A panel of 13 experts were invited to a virtual meeting which took place on 27 March 2021. The proceedings were organised in the sub-sections diagnosis, debridement, infection control, dressings, grafting, pain management, oxygen treatment, outcomes and future needs. Eighty percent or better concurrence among the panellists was considered a consensus. A large number of critical questions were discussed and agreed upon. Important takeaways included that wound care needs to be simplified to a point that it can be delivered by the patient or the patient's family. Another one was that telemonitoring, which has proved very useful during the COVID-19 pandemic, can help reduce the frequency of interventions by a visiting nurse or a wound care center. Defining patient expectations is critical to designing a successful treatment. Patient outcomes might include wound specific outcomes such as time to heal, wound size reduction, as well as improvement in quality of life. For those patients with expectations of healing, an aggressive approach to achieve that goal is recommended. When healing is not an expectation, such as in patients receiving palliative wound care, outcomes might include pain reduction, exudate management, odour management and/or other quality of life benefits to wound care.

The CALCIPHYX study: a randomized, double-blind, placebo-controlled, Phase 3 clinical trial of SNF472 for the treatment of calciphylaxis.

BACKGROUND: Calcific uraemic arteriolopathy (CUA; calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterized by poorly healing or non-healing wounds, and is associated with mortality, substantial morbidity related to infection and typically severe pain. In an open-label Phase 2 clinical trial, SNF472, a selective inhibitor of vascular calcification, was well-tolerated and associated with improvement in wound healing, reduction of wound-related pain and improvement in wound-related quality of life (QoL). Those results informed the design of the CALCIPHYX trial, an ongoing, randomized, placebo-controlled, Phase 3 trial of SNF472 for treatment of calciphylaxis. METHODS: In CALCIPHYX, 66 patients receiving haemodialysis who have an ulcerated calciphylaxis lesion will be randomized 1:1 to double-blind SNF472 (7 mg/kg intravenously) or placebo three times weekly for 12 weeks (Part 1), then receive open-label SNF472 for 12 weeks (Part 2). All patients will receive stable background care, which may include pain medications and sodium thiosulphate, in accordance with the clinical practices of each site. A statistically significant difference between the SNF472 and placebo groups for improvement of either primary endpoint at Week 12 will demonstrate efficacy of SNF472: change in Bates-Jensen Wound Assessment Tool-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related QoL, qualitative changes in wounds, wound size, analgesic use and safety. CONCLUSIONS: This randomized, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing.

Improved healing of chronic diabetic foot wounds in a prospective randomised controlled multi-centre clinical trial with a microvascular tissue allograft.

This study assesses the impact of a processed microvascular tissue (PMVT) allograft on wound closure and healing in a prospective, single-blinded, multi-centre, randomised controlled clinical trial of 100 subjects with Wagner Grade 1 and 2 chronic neuropathic diabetic foot ulcerations. In addition to standard wound care, including standardised offloading, the treatment arm received PMVT while the control arm received a collagen alginate dressing. The primary endpoint was complete wound closure at 12 weeks. Secondary endpoints assessed on all subjects were percent wound area reduction, time to healing, and local neuropathy. Novel exploratory sub-studies were conducted for wound area perfusion and changes in regional neuropathy. Weekly application of PMVT resulted in increased complete wound closure at 12 weeks (74% vs 38%; P = .0003), greater percent wound area reduction from weeks four through 12 (76% vs 24%; P = .009), decreased time to healing (54 days vs 64 days; P = .009), and improved local neuropathy (118% vs 11%; P = .028) compared with the control arm. Enhanced perfusion and improved regional neuropathy were demonstrated in the sub-studies. In conclusion, this study demonstrated increased complete healing with PMVT and supports its use in treating non-healing DFUs. The observed benefit of PMVT on the exploratory regional neuropathy and perfusion endpoints warrants further study.

Development of the BWAT-CUA Scale to Assess Wounds in Patients with Calciphylaxis.

Calcific uremic arteriolopathy (CUA; calciphylaxis) is a severe form of vascular calcification with no approved therapies. A standardized wound assessment tool is needed to evaluate changes in calciphylaxis wounds over time. A prospective, single-arm study of 14 patients with calciphylaxis reported improvement for the primary endpoint of wound healing using the 13-item Bates-Jensen Wound Assessment Tool (BWAT), although that tool was developed for assessment of pressure ulcers. This report describes development of BWAT-CUA, an 8-item modification of BWAT focusing on prototypical features of calciphylaxis lesions. The BWAT-CUA has a range of 8 (best) to 40 (worst) and was used ad hoc to analyze BWAT data collected in the prospective study. Using BWAT-CUA, relative improvement in calciphylaxis wounds was 30% overall (from 21.2 to 14.9; p = 0.0016) and 34% in the subset of 12 patients with ulceration at baseline (from 23.3 to 15.3; p = 0.0002). BWAT-CUA is a primary endpoint in an ongoing randomized, placebo-controlled phase 3 study of SNF472 recruiting patients with end-stage kidney disease and at least one ulcerated calciphylaxis lesion. BWAT-CUA, a newly developed tool for assessment of calciphylaxis wound severity and improvements over time, may be used in clinical research and in clinical practice.

Evidence supporting wound care end points relevant to clinical practice and patients' lives. Part 3: The Patient Survey.

The 2006 U.S. Food and Drug Administration Guidance for Industry emphasizes wound closure as the primary outcome for clinical trials in wound healing. Wound care professionals understand that complete wound healing is not always achievable when evaluating new treatments. FDA, Association for the Advancement of Wound Care, and Wound Healing Society are working collaboratively to identify scientifically achievable, clinically relevant, and patient-centered endpoints with sufficient support to serve as primary outcomes for clinical trials. The Opinion Survey from People with Wounds presented here addresses an important but understudied issue: the gap between clinician, healthcare insurance companies, government agencies, and patient perspectives regarding clinically meaningful and scientifically achievable primary endpoints for wound care. The survey, adapted from the clinician survey with adjustment for health literacy, was pilot tested and revised based on a limited number of patients in a single clinic. After central IRB approval, the on-line survey was administered in English and Spanish and submitted anonymously to a server with the cooperation of multiple wound clinics and societies. Four hundred and thirty-eight patients and caregivers from across the United States responded over a 10-month period. Based on this survey, the most valuable clinical endpoints were reduced infection, recurrence, and amputation. The most valuable quality of life outcomes were increased independence, reduced social isolation, and pain. The top five endpoints in terms of usefulness for measuring clinical trial success were time to heal, wound size, infection, recurrence, and pain. Narrative responses from wound patients emphasized the inability to perform activities of daily living and pain as major factors that impacted their daily lives. Engagement of patients in clinical trials and evaluation of potential treatments is critical to improving wound care. This survey provides insight into the needs of patients with wounds and provides a roadmap for structuring future clinical trials to better meet those needs.

Protease-Resistant Growth Factor Formulations for the Healing of Chronic Wounds.

Objective: Chronic wounds are long-term nonhealing wounds that are refractory to treatment. These wounds can present elevated protease levels, leading to rapid degradation of native and exogenously added growth factors. This work focused on developing a protease-resistant growth factor formulation for treatment of chronic wounds presented with high protease activity. Approach: This study developed protease-resistant growth factor formulations comprising elastin-like peptides (ELPs) fused with a known protease inhibitor peptide or growth factor. The ELP component of the fusion proteins allows assembly of heterogeneous nanoparticles (NPs) putting the inhibitor in close proximity to the growth factor to be protected. Results: We show successful preservation of growth factor activity in high human neutrophil elastase (HNE) environment and in human chronic wound fluid derived from patients. We further show that these NPs result in enhanced collagen remodeling and resolution of inflammation in a full thickness wound supplemented with HNE in genetically diabetic mice. Innovation: Development of heterogeneous NPs that put the protease inhibitor in close proximity of the growth factor. Moreover, the modular nature of the NPs allows for protection of multiple growth factors by the same inhibitor without changing the amino acid sequence of the growth factor. Conclusion: Our results indicate that the developed NPs hold tremendous promise in chronic wound healing therapy and may further help the translation of growth factor therapies to clinic. The customizable template for the NP design allows for multifaceted use across several fields in research and medicine.

Pressure ulcer summit 2018: An interdisciplinary approach to improve our understanding of the risk of pressure-induced tissue damage.

Pressure ulcers (PrUs) affect approximately 2.5 million patients and account for 60,000 deaths annually. They are associated with an additional annual cost of $43,000 per related hospital stay and a total cost to the US health care system as high as $25 billion. Despite the implementation of national and international PrU prevention guidelines and toolkits, rates of facility-acquired PrU s and PrUs in people with spinal cord injury are still high. A new paradigm is needed that distinguishes between prevention and treatment research methods and includes not only the causative factors of pressure and tissue deformation but also patient-specific anatomical differences and the concomitant biological cellular processes, including reperfusion injury, toxic metabolites, ischemia, cell distortion, impaired lymphatic drainage, and impaired interstitial fluid flow that compound existing tissue damage. The purpose of this article is to summarize the highlights from the first annual Pressure Ulcer Summit held February 9-10, 2018 in Atlanta, Georgia (sponsored by the Association for the Advancement of Wound Care in partnership with multiple professional organizations). This international, interdisciplinary summit brought together key stakeholders in wound care and PrU prevention and management to highlight advances in pathophysiology of pressure-induced tissue damage; explore challenges in current terminologies, documentation, and data collection; describe innovations in clinical care; and identify research opportunities to advance the science of PrU prevention and management.

Clinical Achievement of Wound Closure and Tissue Quality With a Novel Microvascular Tissue Graft.

INTRODUCTION: Microvascular tissue serves as the foundation for tissue granulation and remodeling during the wound healing process. Optimal repair of microvascular structure and function is essential for future healing capacity and to minimize tissue breakdown in a newly epithelialized wound. OBJECTIVE: This case series of 3 patients with nonhealing diabetic foot ulcers (DFUs) refractory to standard wound care demonstrates the ability of processed microvascular tissue (PMVT) to enable wound closure, increase local perfusion and vascular maturity, and improve overall tissue quality. MATERIALS AND METHODS: Three patients with nonhealing DFUs ranging from 1.1 cm2 to 11.2 cm2 recalcitrant to standard of care were treated weekly with topical PMVT and standard of care. Wound closure was measured weekly using infrared imaging. Fluorescence microangiography was used to perform dynamic quantification of wound microcirculation and assess the perfusion quality. Ingress rates were measured at 5 defined rectangular regions of interest of the wound to evaluate inflammation and microvascular integrity. RESULTS: All 3 nonhealing DFUs treated with weekly topical PMVT healed within 12 weeks (average, 6.3 ± 5.5 weeks). Assessment of healed wounds at the time of closure indicated PMVT treatment significantly improved perfusion within the newly healed wounded area and throughout the immediate surrounding tissues. No wound recurrence or tissue deterioration has been observed in more than 9 months of follow-up. CONCLUSIONS: In this series of patients, the PMVT graft demonstrated improved wound closure, increased local perfusion and vascular maturity, and improved tissue quality. This graft is a promising advanced tissue therapy for nonhealing DFUs and other complex wounds. It is now the subject of a randomized controlled trial.

Use of mechanically powered disposable negative pressure wound therapy: recommendations and reimbursement update.

Use of ultra-portable, mechanically powered disposable negative pressure wound therapy (dNPWT) has grown as an adjunctive modality to manage wounds in outpatient care and to expedite transition of inpatients to an outpatient setting. This technology has demonstrated similar efficacy and usability for mobile outpatients when compared with electrically powered negative pressure wound therapy devices. It was designed for patients with smaller, low to moderately exudating wounds and does not require batteries or a power source. However, very few studies address best practices for using dNPWT in a variety of wound types. There is a need for comprehensive clinical recommendations to better direct clinicians and patients in using this therapy. In addition, it is critical that providers are knowledgeable about processes for obtaining reimbursement for placement of dNPWT since codes and procedures differ drastically from standard NPWT. A panel meeting of experts with a high level of experience with dNPWT in varied wound types was convened to develop clinical recommendations and summarize current US reimbursement coding guidelines for the use of dNPWT. This publication summarizes the recommendations from panel members, in addition to supporting evidence, to help guide appropriate use of dNPWT. Panel recommendations regarding optimal patient and wound selection, wound preparation, proper patient training, and use of dNPWT in various wound types are included as well as clinical techniques for dressing application, bridging under offloading devices and compression, maintaining a seal, and protecting intact skin. Processes and codes for obtaining reimbursement for dNPWT are reviewed by care setting. Clinical recommendations and reimbursement guidelines summarized in this publication are meant to provide direction to clinicians in using dNPWT that potentially could translate into improved clinical and economic value.

Evidence supporting wound care end points relevant to clinical practice and patients' lives. Part 2. Literature survey.

Patients with wounds bear significant clinical, personal, and economic burdens yet complete wound healing is the only United States Food and Drug Administration (FDA) recognized primary clinical trial end point. The overall goal of this project is to work with FDA to expand the list of acceptable primary end points, recognizing that new and innovative treatments, devices, and drugs may not have complete healing as the focus. Part 1 of the project surveyed 628 wound care experts who identified and content-validated 15 end points most relevant to clinical practice and benefitting patients' lives as primary outcomes in clinical trials. Part 2 is focused on critical appraisal of the evidence in the wound care literature supporting FDA criteria to qualify these 15 end points as primary end points in clinical trials. Further research involved systematic review of the literature regarding the most promising end points. Forty volunteer, interdisciplinary, wound healing experts in fields related to the end points compiled evidence from systematic MEDLINE searches and society databases supporting the FDA criteria of reliability, clinical construct validity, capacity to detect concurrent or longitudinal change, and responder analysis. The search revealed 485 references involving over 462,000 subjects supporting FDA-required parameters for all 15 end points More than 50 references supported FDA-required parameters qualifying the following outcomes for use in clinical trials supporting interventions for FDA clearance: Pain reduction, Physical function and ambulation, Infection reduction, Time to heal, and Percent wound area reduction in 4-8 weeks. Among these, only Time to heal is currently recognized by the FDA as a primary wound outcome in clinical trials. These results suggest that wound science is already serving patients and professionals by improving these content-validated outcomes that merit regulatory consideration.

Human Adipose-Derived Stem Cell Conditioned Media and Exosomes Containing MALAT1 Promote Human Dermal Fibroblast Migration and Ischemic Wound Healing.

Objective: Chronically ill patients heal recalcitrant ulcerative wounds more slowly. Human adipose-derived stem cells (hADSCs) play an important role in tissue regeneration and exosomes secreted by hADSC contribute to their paracrine signaling. In addition to cytokines, lipids and growth factors, hADSC secrete mRNA, miRNA, and long noncoding (lnc) RNA into exosomes. In this study we examined the role of lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), an abundant lncRNA in exosomes from conditioned media (CM), on cell migration and ischemic wound healing. Approach: CM and isolated exosomes from hADSC were applied to human dermal fibroblast (HDF) in scratch assays and electric cell-substrate impedance sensing (ECIS) assays. CM was also applied to a rat model of ischemic wound healing and wound closure was followed. Results: CM stimulated cell migration of HDFs in vitro by 48%. CM stimulated the closure of ischemic wounds in a rat model 50% faster than unconditioned media. The depletion of MALAT1 in adipose-derived stem cell (ADSC) CM significantly reduced cell migration. Since MALAT1 is secreted into exosomes, a purified population of exosomes was applied to HDF where they enhanced cell migration in a similar manner to FGF-2 or basic fibroblast growth factor (bFGF) in ECIS wound healing assays. The uptake of exosomes by HDF was shown using dynasore, an inhibitor that blocks clathrin- and caveolin-dependent endocytosis. Depletion of MALAT1 in hADSC with antisense oligonucleotides resulted in exosomes without MALAT1. These exosomes had an effect similar to the unconditioned, control media in ECIS assays. Innovation: Exosomes contain lncRNA MALAT1 and other factors that have the potential to stimulate HDF cell migration and angiogenesis involved in wound healing without applying stem cells to wounds. Conclusion: Our results show the potential of using topically applied ADSC-derived exosomes containing MALAT1 for treating ischemic wounds. This allows for harnessing the power of stem cell paracrine signaling capabilities without applying the cells.

Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory evaluation.