The Micrograft Concept for Wound Healing: Strategies and Applications

Biswas, Amit K.; Bharara, Manish; Hurst, Craig A.; Armstrong, David G.; Rilo, Horacio

doi:10.1177/193229681000400407

Cited by 38 publications

(32 citation statements)

References 102 publications

(109 reference statements)

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“…The concept of micrografting or transplanting small particles of skin to accelerate wound healing is relatively old. The pinch‐grafting technique was first described by Reverdin in 1869 and since then many other techniques have been developed for a similar purpose . Most of these early attempts were associated with labor‐intensive or time‐consuming methodology, which limited widespread adoption of this therapeutic approach .…”

mentioning

confidence: 99%

“…The pinch‐grafting technique was first described by Reverdin in 1869 and since then many other techniques have been developed for a similar purpose . Most of these early attempts were associated with labor‐intensive or time‐consuming methodology, which limited widespread adoption of this therapeutic approach . Lately, there has been a push towards developing modifications of autologous skin grafts to address limitations of STSG and pitfalls of early attempts in micrografting .…”

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confidence: 99%

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Accelerated epithelialization and improved wound healing metrics in porcine full‐thickness wounds transplanted with full‐thickness skin micrografts

Rettinger

Fletcher

Carlsson

et al. 2017

Wound Repair Regeneration

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Split-thickness skin grafting (STSG) is the current gold standard for treatment of extensive burn and traumatic skin injuries. However, STSG is limited by donor-site morbidity and availability, and often leads to scarring and wound contracture. Furthermore, these thin grafts lack dermal elements such as nerves and adnexa which are important in recapitulating normal skin function. Methods of fractional skin replacement either as minced STSGs or microscopic skin tissue columns have been proposed, though these techniques have not been fully characterized and lack evidence of regenerated adnexal structures. Here, we describe an alternative method of fractional skin replacement using full-thickness skin micrografts containing deep dermal components and intact adnexa. Full-thickness wounds measuring 3 cm in diameter and 2 cm apart were created on adult female Yorkshire swine. Full-thickness skin tissue columns (FTSTCs) 1.5 mm in diameter with intact adnexa and subcutaneous tissue were obtained using a suction-assisted device. Explant culture was initiated to demonstrate the capacity of FTSTCs to act as reservoirs of viable and proliferative epidermal and dermal cells. FTSTCs were applied directly to excisional wounds at three different expansion ratios (1:16, 1:40, 1:100) in fibrin sealant. Biopsies were collected at defined time points postwounding and processed for histology and immunohistochemistry. Wounds grafted with FTSTCs showed enhanced reepithelialization and epidermal differentiation over untreated control wounds in a dosage dependent manner. Adnexal structures such as hair follicles and sweat glands were only evident in FTSTC-treated wounds. Furthermore, whereas ungrafted wounds were marked by extensive infiltration of α-Smooth Muscle Actin (α-SMA ) myofibroblasts at POD 60, α-SMA expression was sparse and largely limited to perivascular cells in FTSTC-treated wounds. The number of Ki67 cells was also greatly reduced in FTSTC-treated wounds. Transplantation of FTSTCs containing intact adnexa improved wound healing parameters in porcine full-thickness wounds and may have implications for the treatment of large, traumatic wounds.

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confidence: 99%

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confidence: 99%

Accelerated epithelialization and improved wound healing metrics in porcine full‐thickness wounds transplanted with full‐thickness skin micrografts

Rettinger

Fletcher

Carlsson

et al. 2017

Wound Repair Regeneration

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“…Moreover, this technique is associated with distress, pain, and hypertrophic scar formation [15]. Over the past years, great advances have been made in micrograft (MG) treatments, of which many have shown promising results in the clinical setting [16]. Compared to the conventional skin graft methods, the micrograft technique comprises of viable microtissue fragments that are directly applied to the site of injury.…”

Section: Introductionmentioning

confidence: 99%

Activator Protein-1 Transcriptional Activity Drives Soluble Micrograft-Mediated Cell Migration and Promotes the Matrix Remodeling Machinery

Balli

Chui

Athanasouli

et al. 2019

Stem Cells International

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Impaired wound healing and tissue regeneration have severe consequences on the patient’s quality of life. Micrograft therapies are emerging as promising and affordable alternatives to improve skin regeneration by enhancing the endogenous wound repair processes. However, the molecular mechanisms underpinning the beneficial effects of the micrograft treatments remain largely unknown. In this study, we identified the active protein-1 (AP-1) member Fos-related antigen-1 (Fra-1) to play a central role in the extracellular signal-regulated kinase- (ERK-) mediated enhanced cell migratory capacity of soluble micrograft-treated mouse adult fibroblasts and in the human keratinocyte cell model. Accordingly, we show that increased micrograft-dependent in vitro cell migration and matrix metalloprotease activity is abolished upon inhibition of AP-1. Furthermore, soluble micrograft treatment leads to increased expression and posttranslational phosphorylation of Fra-1 and c-Jun, resulting in the upregulation of wound healing-associated genes mainly involved in the regulation of cell migration. Collectively, our work provides insights into the molecular mechanisms behind the cell-free micrograft treatment, which might contribute to future advances in wound repair therapies.

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“…In the United States alone, approximately 3 to 6 million patients suffer from such wounds and an increasing number of patients are treated insufficiently over protracted courses, costing an estimated $5 to $10 billion each year [1]. The use of split-thickness or full thickness skin grafts offers a reasonable solution; however, it is limited by donor site availability, poor healing at the donor site, and painful skin harvesting procedures that require general anesthesia and a trip to the operating room [2-3]. Alternatively, artificially engineered skin and allograft or xenograft provide rapid but temporary coverage and are often prohibitively expensive with unreliable outcomes.…”

Section: Introductionmentioning

confidence: 99%

A Case Series of Complex Recalcitrant Wounds Treated with Epidermal Grafts Harvested from an Automated Device

Cai

Gowda

Chopra

et al. 2016

Cureus

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Introduction: Epidermal grafting has several advantages over full-thickness or split-thickness grafts in the treatment of complex non-healing wounds. These include the low risk of donor site complications, minimal patient discomfort, and abstention from the operating room. Traditionally, the lack of reliable epidermal harvesting techniques has limited its clinical utilization. The development of an automated suction blister epidermal graft (SBEG) harvesting device may facilitate clinical utilization of this technique. The authors present a case series of multimorbid patients who were poor surgical candidates and were treated with this technique.Methods: A retrospective review of all patients treated with CelluTome™ Epidermal Harvesting System (KCI, an Acelity company, San Antonio, TX) prior to May 2016 at our institution was conducted.Results: A total of 12 patients underwent 14 epidermal grafting procedures. Multiple comorbidities were identified, including smoking (33%), immunosuppression by immunotherapy or steroids (25%), chronic venous insufficiency (25%), diabetes mellitus (25%), malignancy (25%), polysubstance abuse (17%), HIV/AIDS (17%), and peripheral artery disease (8%). Among the two acute wounds (≤ 3 months) and 10 chronic wounds, the average wound size was 49.1 cm2 (± 77.6 cm2) and the median wound duration was 5.7 months (interquartile range: 4.1 - 15.8 months) before SBEG was attempted. These complex wounds had failed prior therapies, such as local wound care (100%), incision and drainage (58%), vacuum-assisted closure (33%), split-thickness skin graft (16%), and hyperbaric oxygen (8%). Following the procedure, all donor sites healed within one week. Three patients were lost to follow-up. Of the remaining nine patients, four patients had complete resolution of their wounds at a median follow-up of 13.1 weeks (interquartile range: 6.8-17.3 weeks). Among those with partial resolutions, the average wound size was 4.2 cm2 (± 2.1 cm2) with an average wound reduction of 79% (± 23%). No donor or recipient site complications were observed.Conclusions: The automated SBEG harvesting device is an effective and safe option for treating complex non-healing wounds in multimorbid patients who may be poor surgical candidates. This procedure demonstrates minimal contraindications to its use and donor or recipient site complications.

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The Micrograft Concept for Wound Healing: Strategies and Applications

Cited by 38 publications

References 102 publications

Accelerated epithelialization and improved wound healing metrics in porcine full‐thickness wounds transplanted with full‐thickness skin micrografts

Accelerated epithelialization and improved wound healing metrics in porcine full‐thickness wounds transplanted with full‐thickness skin micrografts

Activator Protein-1 Transcriptional Activity Drives Soluble Micrograft-Mediated Cell Migration and Promotes the Matrix Remodeling Machinery

A Case Series of Complex Recalcitrant Wounds Treated with Epidermal Grafts Harvested from an Automated Device

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