Epidermal Regeneration by Micrograft Transplantation with Immediate 100-Fold Expansion

Hackl, Florian; Bergmann, Juri; Granter, Scott R.; Koyama, Tadanobu; Kiwanuka, Elizabeth; Zuhaili, Baraa; Pomahac, Bohdan; Caterson, Edward J.; Junker, Johan P.E.; Eriksson, Elof

doi:10.1097/prs.0b013e318241289c

Cited by 58 publications

(30 citation statements)

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“…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 . In a study conducted by Hackl et al, skin micrografts 0.8 mm 2 in size were transplanted and spread evenly over a full‐thickness wound bed with the expansion ratio of 1:100 .…”

mentioning

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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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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mentioning

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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“…This did not include full‐thickness skin, however. Since then many alternative techniques have been developed to apply this concept, including mincing split‐thickness grafts into smaller pieces (Meek, ; Hackl et al , ) and enzymatically digesting split‐thickness skin into single‐cell suspensions (Fraulin et al , ; Navarro et al , ). These techniques also fail to transfer full‐thickness skin structures, and lead to a donor site wounds that heal with scarring.…”

Section: Discussionmentioning

confidence: 99%

“…Fortunately, there are many existing clinical options for providing temporary barrier function, from various bandages and dressings to advanced biomaterials. In particular, dressing regimens that maintain a moist wound environment have been shown to enable the engraftment of split‐thickness skin grafts with no detrimental effects, even when the grafts were placed upside‐down, as keratinocytes are able to migrate from the base of the wound up to the surface, where they then participate in wound re‐epithelialization (Hackl et al , ; Zuhaili et al , ). This is salient because the skin columns in our study reported here were also applied randomly into wounds, without maintaining the epidermis‐up orientation of normal skin.…”

Section: Discussionmentioning

confidence: 99%

Reconstitution of full-thickness skin by microcolumn grafting

Tam

Wang

Vuong

et al. 2016

J Tissue Eng Regen Med

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In addition to providing a physical barrier, skin also serves a diverse range of physiological functions through different specialized resident cell types/structures, including melanocytes (pigmentation and protection against ultraviolet radiation), Langerhans cells (adaptive immunity), fibroblasts (maintaining extracellular matrix, paracrine regulation of keratinocytes), sweat glands (thermoregulation) and hair follicles (hair growth, sensation and a stem cell reservoir). Restoration of these functional elements has been a long‐standing challenge in efforts to engineer skin tissue, while autologous skin grafting is limited by the scarcity of donor site skin and morbidity caused by skin harvesting. We demonstrate an alternative approach of harvesting and then implanting μm‐scale, full‐thickness columns of human skin tissue, which can be removed from a donor site with minimal morbidity and no scarring. Fresh human skin microcolumns were used to reconstitute skin in wounds on immunodeficient mice. The restored skin recapitulated many key features of normal human skin tissue, including epidermal architecture, diverse skin cell populations, adnexal structures and sweat production in response to cholinergic stimulation. These promising preclinical results suggest that harvesting and grafting of microcolumns may be useful for reconstituting fully functional skin in human wounds, without donor site morbidity. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

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“…Zuhaili et al demonstrated that in a wet environment split‐thickness skin grafts can survive even when placed with the dermis facing away from the wound surface. Hackl et al showed that a wet or a moist environment improved reepithelialization and decreased contracture in wounds treated with minced skin micrografts and further demonstrated that the micrografts survived regardless of orientation (dermis up or down).…”

Section: Hydrationmentioning

confidence: 99%

The external microenvironment of healing skin wounds

Kruse

Nuutila

Lee

et al. 2015

Wound Repair Regeneration

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The skin wound microenvironment can be divided into two main components that influence healing: the external wound microenvironment, which is outside the wound surface; and the internal wound microenvironment, underneath the surface, to which the cells within the wound are exposed. Treatment methods that directly alter the features of the external wound microenvironment indirectly affect the internal wound microenvironment due to the exchange between the two compartments. In this review, we focus on the effects of temperature, pressure (positive and negative), hydration, gases (oxygen and carbon dioxide), pH, and anti-microbial treatment on the wound. These factors are well described in the literature and can be modified with treatment methods available in the clinic. Understanding the roles of these factors in wound pathophysiology is of central importance in wound treatment.

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Epidermal Regeneration by Micrograft Transplantation with Immediate 100-Fold Expansion

Abstract: Minced skin micrografts are very effective in wound repair and can provide 100-fold expansion of a skin graft. Early clinical results confirm the utility of this technique.

Cited by 58 publications

References 0 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

Reconstitution of full-thickness skin by microcolumn grafting

The external microenvironment of healing skin wounds

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