Cellular versus acellular matrix devices in treatment of diabetic foot ulcers

Study protocol for a comparative efficacy randomized controlled trial

Hadar Lev-Tov, Chin-Shang Li, Sara Dahle, Roslyn Rivkah Isseroff

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: Diabetic foot ulcers (DFUs) represent a significant source of morbidity and an enormous financial burden. Standard care for DFUs involves systemic glucose control, ensuring adequate perfusion, debridement of nonviable tissue, off-loading, control of infection, local wound care and patient education, all administered by a multidisciplinary team. Unfortunately, even with the best standard of care (SOC) available, only 24% or 30% of DFUs will heal at weeks 12 or 20, respectively.The extracellular matrix (ECM) in DFUs is abnormal and its impairment has been proposed as a key target for new therapeutic devices. These devices intend to replace the aberrant ECM by implanting a matrix, either devoid of cells or enhanced with fibroblasts, keratinocytes or both as well as various growth factors. These new bioengineered skin substitutes are proposed to encourage angiogenesis and in-growth of new tissue, and to utilize living cells to generate cytokines needed for wound repair.To date, the efficacy of bioengineered ECM containing live cellular elements for improving healing above that of a SOC control group has not been compared with the efficacy of an ECM devoid of cells relative to the same SOC. Our hypothesis is that there is no difference in the improved healing effected by either of these two product types relative to SOC.Methods/Design: To test this hypothesis we propose a randomized, single-blind, clinical trial with three arms: SOC, SOC plus Dermagraft® (bioengineered ECM containing living fibroblasts) and SOC plus Oasis® (ECM devoid of living cells) in patients with nonhealing DFUs. The primary outcome is the percentage of subjects that achieved complete wound closure by week 12.Discussion: If our hypothesis is correct, then immense cost savings could be realized by using the orders-of-magnitude less expensive acellular ECM device without compromising patient health outcomes. The article describes the protocol proposed to test our hypothesis.Trial registration: ClinicalTrials.gov: NCT01450943. Registered: 7 October 2011.

Original languageEnglish (US)
Article number8
JournalTrials
Volume14
Issue number1
DOIs
StatePublished - Jan 9 2013

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Diabetic Foot
Standard of Care
Extracellular Matrix
Randomized Controlled Trials
Equipment and Supplies
Fibroblasts
Artificial Skin
Cost Savings
Wounds and Injuries
Debridement
Wound Infection
Patient Education
Infection Control
Keratinocytes
Intercellular Signaling Peptides and Proteins
Perfusion
Clinical Trials
Cytokines
Morbidity
Glucose

Keywords

  • Chronic wounds
  • Dermagraft
  • Diabetic foot ulcer
  • Nonhealing wounds
  • Oasis
  • Wound matrix

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

Cite this

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title = "Cellular versus acellular matrix devices in treatment of diabetic foot ulcers: Study protocol for a comparative efficacy randomized controlled trial",
abstract = "Background: Diabetic foot ulcers (DFUs) represent a significant source of morbidity and an enormous financial burden. Standard care for DFUs involves systemic glucose control, ensuring adequate perfusion, debridement of nonviable tissue, off-loading, control of infection, local wound care and patient education, all administered by a multidisciplinary team. Unfortunately, even with the best standard of care (SOC) available, only 24{\%} or 30{\%} of DFUs will heal at weeks 12 or 20, respectively.The extracellular matrix (ECM) in DFUs is abnormal and its impairment has been proposed as a key target for new therapeutic devices. These devices intend to replace the aberrant ECM by implanting a matrix, either devoid of cells or enhanced with fibroblasts, keratinocytes or both as well as various growth factors. These new bioengineered skin substitutes are proposed to encourage angiogenesis and in-growth of new tissue, and to utilize living cells to generate cytokines needed for wound repair.To date, the efficacy of bioengineered ECM containing live cellular elements for improving healing above that of a SOC control group has not been compared with the efficacy of an ECM devoid of cells relative to the same SOC. Our hypothesis is that there is no difference in the improved healing effected by either of these two product types relative to SOC.Methods/Design: To test this hypothesis we propose a randomized, single-blind, clinical trial with three arms: SOC, SOC plus Dermagraft{\circledR} (bioengineered ECM containing living fibroblasts) and SOC plus Oasis{\circledR} (ECM devoid of living cells) in patients with nonhealing DFUs. The primary outcome is the percentage of subjects that achieved complete wound closure by week 12.Discussion: If our hypothesis is correct, then immense cost savings could be realized by using the orders-of-magnitude less expensive acellular ECM device without compromising patient health outcomes. The article describes the protocol proposed to test our hypothesis.Trial registration: ClinicalTrials.gov: NCT01450943. Registered: 7 October 2011.",
keywords = "Chronic wounds, Dermagraft, Diabetic foot ulcer, Nonhealing wounds, Oasis, Wound matrix",
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T2 - Study protocol for a comparative efficacy randomized controlled trial

AU - Lev-Tov, Hadar

AU - Li, Chin-Shang

AU - Dahle, Sara

AU - Isseroff, Roslyn Rivkah

PY - 2013/1/9

Y1 - 2013/1/9

N2 - Background: Diabetic foot ulcers (DFUs) represent a significant source of morbidity and an enormous financial burden. Standard care for DFUs involves systemic glucose control, ensuring adequate perfusion, debridement of nonviable tissue, off-loading, control of infection, local wound care and patient education, all administered by a multidisciplinary team. Unfortunately, even with the best standard of care (SOC) available, only 24% or 30% of DFUs will heal at weeks 12 or 20, respectively.The extracellular matrix (ECM) in DFUs is abnormal and its impairment has been proposed as a key target for new therapeutic devices. These devices intend to replace the aberrant ECM by implanting a matrix, either devoid of cells or enhanced with fibroblasts, keratinocytes or both as well as various growth factors. These new bioengineered skin substitutes are proposed to encourage angiogenesis and in-growth of new tissue, and to utilize living cells to generate cytokines needed for wound repair.To date, the efficacy of bioengineered ECM containing live cellular elements for improving healing above that of a SOC control group has not been compared with the efficacy of an ECM devoid of cells relative to the same SOC. Our hypothesis is that there is no difference in the improved healing effected by either of these two product types relative to SOC.Methods/Design: To test this hypothesis we propose a randomized, single-blind, clinical trial with three arms: SOC, SOC plus Dermagraft® (bioengineered ECM containing living fibroblasts) and SOC plus Oasis® (ECM devoid of living cells) in patients with nonhealing DFUs. The primary outcome is the percentage of subjects that achieved complete wound closure by week 12.Discussion: If our hypothesis is correct, then immense cost savings could be realized by using the orders-of-magnitude less expensive acellular ECM device without compromising patient health outcomes. The article describes the protocol proposed to test our hypothesis.Trial registration: ClinicalTrials.gov: NCT01450943. Registered: 7 October 2011.

AB - Background: Diabetic foot ulcers (DFUs) represent a significant source of morbidity and an enormous financial burden. Standard care for DFUs involves systemic glucose control, ensuring adequate perfusion, debridement of nonviable tissue, off-loading, control of infection, local wound care and patient education, all administered by a multidisciplinary team. Unfortunately, even with the best standard of care (SOC) available, only 24% or 30% of DFUs will heal at weeks 12 or 20, respectively.The extracellular matrix (ECM) in DFUs is abnormal and its impairment has been proposed as a key target for new therapeutic devices. These devices intend to replace the aberrant ECM by implanting a matrix, either devoid of cells or enhanced with fibroblasts, keratinocytes or both as well as various growth factors. These new bioengineered skin substitutes are proposed to encourage angiogenesis and in-growth of new tissue, and to utilize living cells to generate cytokines needed for wound repair.To date, the efficacy of bioengineered ECM containing live cellular elements for improving healing above that of a SOC control group has not been compared with the efficacy of an ECM devoid of cells relative to the same SOC. Our hypothesis is that there is no difference in the improved healing effected by either of these two product types relative to SOC.Methods/Design: To test this hypothesis we propose a randomized, single-blind, clinical trial with three arms: SOC, SOC plus Dermagraft® (bioengineered ECM containing living fibroblasts) and SOC plus Oasis® (ECM devoid of living cells) in patients with nonhealing DFUs. The primary outcome is the percentage of subjects that achieved complete wound closure by week 12.Discussion: If our hypothesis is correct, then immense cost savings could be realized by using the orders-of-magnitude less expensive acellular ECM device without compromising patient health outcomes. The article describes the protocol proposed to test our hypothesis.Trial registration: ClinicalTrials.gov: NCT01450943. Registered: 7 October 2011.

KW - Chronic wounds

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KW - Nonhealing wounds

KW - Oasis

KW - Wound matrix

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