Mechanical offloading of incisional wounds is associated with transcriptional downregulation of inflammatory pathways in a large animal model

Januszyk, Michael; Wong, Victor W.; Bhatt, Kirit A.; Vial, Ivan N.; Paterno, Josemaria; Longaker, Michael T.; Gurtner, Geoffrey C.

doi:10.4161/org.28818

Cited by 34 publications

(27 citation statements)

References 27 publications

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“…These characteristics are similar to those found in the features of Ambystoma mexicanum . We postulate that fetal scarless healing may be the result of an anti‐inflammatory effect due to its innately low resting tension environment …”

Section: Learning From Nature: Different Animal Species Different Stsupporting

confidence: 81%

The tension biology of wound healing

Harn

Ogawa

Hsu

et al. 2017

Experimental Dermatology

136

110

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Following skin wounding, the healing outcome can be: regeneration, repair with normal scar tissue, repair with hypertrophic scar tissue or the formation of keloids. The role of chemical factors in wound healing has been extensively explored, and while there is evidence suggesting the role of mechanical forces, its influence is much less well defined. Here, we provide a brief review on the recent progress of the role of mechanical force in skin wound healing by comparing laboratory mice, African spiny mice, fetal wound healing and adult scar keloid formation. A comparison across different species may provide insight into key regulators. Interestingly, some findings suggest tension can induce an immune response, and this provides a new link between mechanical and chemical forces. Clinically, manipulating skin tension has been demonstrated to be effective for scar prevention and treatment, but not for tissue regeneration. Utilising this knowledge, specialists may modulate regulatory factors and develop therapeutic strategies to reduce scar formation and promote regeneration. K E Y W O R D Smechanobiology, regeneration, scar, tension, wound

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Section: Learning From Nature: Different Animal Species Different Stsupporting

confidence: 81%

The tension biology of wound healing

Harn

Ogawa

Hsu

et al. 2017

Experimental Dermatology

136

110

View full text Add to dashboard Cite

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“…In preclinical and clinical studies, off-loading of mechanical strain using stress-shielding devices in incisional and excisional wounds has proven to be effective in inhibiting scar development in large animals and humans (Gurtner et al, 2011;Januszyk et al, 2014). Approaches to physically reduce mechanical strain, however, are not applicable to large areas of wounds resulting from extensive burns, traumatic blast injuries, or excisional skin surgeries.…”

Section: Introductionmentioning

confidence: 99%

Controlled Delivery of a Focal Adhesion Kinase Inhibitor Results in Accelerated Wound Closure with Decreased Scar Formation

Kwon

Padmanabhan

et al. 2018

Journal of Investigative Dermatology

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Formation of scars after wounding or trauma represents a significant health care burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, because of the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries. To address this issue, we have developed a pullulan collagen-based hydrogel to deliver FAKI to excisional and burn wounds in mice. Specifically, two distinct drug-laden hydrogels were developed for rapid or sustained release of FAKI for treatment of burn wounds and excisional wounds, respectively. Controlled delivery of FAKI via pullulan collagen hydrogels accelerated wound healing and reduced collagen deposition and activation of scar-forming myofibroblasts in both wound healing models. Our study highlights a biomaterial-based drug delivery approach for wound and scar management that has significant translational implications.

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“…55 There have been several publications that demonstrate how skin responds to biomechanical cues and which biomechanical signal mediators are important in mechanotransduction. [56][57][58][59][60][61][62] The known intracellular mechanisms involved in mechanotransduction are summarized in Fig. 2.…”

Section: Mechanotransduction In the Wound Environmentmentioning

confidence: 99%

Mechanical Forces in Cutaneous Wound Healing: Emerging Therapies to Minimize Scar Formation

Barnes

Marshall

Leavitt

et al. 2018

Advances in Wound Care

163

131

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Significance: Excessive scarring is major clinical and financial burden in the United States. Improved therapies are necessary to reduce scarring, especially in patients affected by hypertrophic and keloid scars. Recent Advances: Advances in our understanding of mechanical forces in the wound environment enable us to target mechanical forces to minimize scar formation. Fetal wounds experience much lower resting stress when compared with adult wounds, and they heal without scars. Therapies that modulate mechanical forces in the wound environment are able to reduce scar size. Critical Issues: Increased mechanical stresses in the wound environment induce hypertrophic scarring via activation of mechanotransduction pathways. Mechanical stimulation modulates integrin, Wingless-type, protein kinase B, and focal adhesion kinase, resulting in cell proliferation and, ultimately, fibrosis. Therefore, the development of therapies that reduce mechanical forces in the wound environment would decrease the risk of developing excessive scars. Future Directions: The development of novel mechanotherapies is necessary to minimize scar formation and advance adult wound healing toward the scarless ideal. Mechanotransduction pathways are potential targets to reduce excessive scar formation, and thus, continued studies on therapies that utilize mechanical offloading and mechanomodulation are needed.

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Mechanical offloading of incisional wounds is associated with transcriptional downregulation of inflammatory pathways in a large animal model

Cited by 34 publications

References 27 publications

The tension biology of wound healing

The tension biology of wound healing

Controlled Delivery of a Focal Adhesion Kinase Inhibitor Results in Accelerated Wound Closure with Decreased Scar Formation

Mechanical Forces in Cutaneous Wound Healing: Emerging Therapies to Minimize Scar Formation

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