Laboratory Models for the Study of Normal and Pathologic Wound Healing

Boyko, Tatiana; Longaker, Michael T.; Yang, George P.

doi:10.1097/prs.0000000000003077

Cited by 31 publications

(20 citation statements)

References 78 publications

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“…The physiological complexity of wound healing indicates that the widely employed in vitro scratch wound assays ( Boyko et al. , 2017 ) should be supplemented by in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

Requirement for and polarized localization of integrin proteins duringDrosophilawound closure

Park

Lee

et al. 2018

MBoC

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Wound reepithelialization is an evolutionarily conserved process in which skin cells migrate as sheets to heal the breach and is critical to prevent infection but impaired in chronic wounds. Integrin heterodimers mediate attachment between epithelia and underlying extracellular matrix and also act in large signaling complexes. The complexity of the mammalian wound environment and evident redundancy among integrins has impeded determination of their specific contributions to reepithelialization. Taking advantage of the genetic tools and smaller number of integrins in Drosophila, we undertook a systematic in vivo analysis of integrin requirements in the reepithelialization of skin wounds in the larva. We identify αPS2-βPS and αPS3-βPS as the crucial integrin dimers and talin as the only integrin adhesion component required for reepithelialization. The integrins rapidly accumulate in a JNK-dependent manner in a few rows of cells surrounding a wound. Intriguingly, the integrins localize to the distal margin in these cells, instead of the frontal or lamellipodial distribution expected for proteins providing traction and recruit nonmuscle myosin II to the same location. These findings indicate that signaling roles of integrins may be important for epithelial polarization around wounds and lay the groundwork for using Drosophila to better understand integrin contributions to reepithelialization.

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“…The physiological complexity of wound healing indicates that the widely employed in vitro scratch wound assays ( Boyko et al. , 2017 ) should be supplemented by in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

Requirement for and polarized localization of integrin proteins duringDrosophilawound closure

Park

Lee

et al. 2018

MBoC

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“…14 Additionally, there are vast differences in wound healing between mice and humans (contraction of tissue in mice vs. reepithelialization in human skin), as well as in hair follicle density and location of sweat glands, further complicating the translation of animal studies. 15,16 The important contribution of sweat glands to reepithelialization of wounds in humans was highlighted in a study showing that the sweat glands, which are present in skin at a density that is almost threefold the density of hair follicles, extensively contribute to wound reepithelialization. 17 This finding further emphasizes the concerns regarding the translation of prior research conducted in animals whose eccrine glands are absent, or significantly limited in presence.…”

mentioning

confidence: 99%

Discordance between histologic and visual assessment of tissue viability in excised burn wound tissue

Karim

Yan

Ocotl

et al. 2018

Wound Repair Regeneration

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The regenerative capacity of burn wounds, and the need for surgical intervention, depends on wound depth. Clinical visual assessment is considered the gold standard for burn depth assessment but it remains a subjective and inaccurate method for tissue evaluation. The purpose of this study was to compare visual assessment with microscopic and molecular techniques for human burn depth determination, and illustrate differences in the evaluation of tissue for potential regenerative capacity. Using intraoperative visual assessment, patients were identified as having deep partial thickness or full thickness burn wounds. Tangential excisions of burn tissue were processed with hematoxylin and eosin to visualize tissue morphology, lactate dehydrogenase assay to ascertain cellular viability, and Keratin‐15 and Ki67 to identify epidermal progenitor cells and proliferative capacity, respectively. RNA from deep partial and full thickness burn tissue as well as normal tissue controls were submitted for RNA sequencing. Lactate dehydrogenase, Keratin‐15, and Ki67 were found throughout the excised burn wound tissue in both deep partial thickness burn tissues and in the second tangential excision of full thickness burn tissues. RNA sequencing demonstrated regenerative capacity in both deep partial and full thickness burn tissue, however a greater capacity for regeneration was present in deep partial thickness compared with full thickness burn tissues. In this study, we highlight the discordance that exists between the intraoperative clinical identification of burn injury depth, and microscopic and molecular determination of viability and regenerative capacity. Current methods utilizing visual assessment for depth of injury are imprecise, and can lead to removal of viable tissue. Additionally, hematoxylin and eosin microscopic analysis should not be used as the sole method in research or clinical determination of depth, as there are no differences in staining between viable and nonviable tissue.

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“…Diabetes mellitus (DM) is a major cause of human chronic wounds (Eming et al, 2014). Several rodent models of DM are available (Ansell et al, 2012;Boyko et al, 2017;Davidson, 1998); however, the streptozotocin (STZ)-induced DM model is almost exclusively used to model type 1 DM (Goodson and Hung, 1977). Like other wound models, there is an inherent lack of consistency between published STZ-DM studies with variation in animal gender, wound size, and wound type, but also in the length of time between DM induction and subsequent injury (Table 1).…”

Section: To the Editormentioning

confidence: 99%