Compromised wound healing can lead to ‘scarring, disease progression and even oncogenesis.’

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Cells can sense polarity in that they know which way is ‘up’. Polarity is vital for the restoration and function of tissue integrity, particularly during tissue repair and wound closure but, also prevents cell damage as a result of mechanical load.

Main header picture. Fibroblast cells. blue nucleus, green tubulin (microtubules) and red actin with gap junctions connecting cells together by stained electron microscopy (Davidson, nd).

Guzmán-Herrera and Mao (2020) discuss how cells are biased to a specific orientation along axes from head to foot, side to side and back to front. In this way, cells fit together promoting tissue integrity and biotensegrity.

Cell Polarity

In the proper polar formation, gap junctions allow the transfer of information about the cells internal and external environment. A gap junction is a connection between cells, just as if the cells were holding hands. Information is passed through these gap junctions such as a mechanical load from body movement, or lack thereof, injury as well as information regarding other vital tissue functions (Guzmán-Herrera and Mao 2020).

Cell motility with a leading and a trailing end. Adapted from Mattila and Lappalainen, (2008).

When a wound occurs, a cascade reaction occurs. In the surrounding tissues, protein kinases begin to regulate the tissues. The cells being to form a ring of rapidly dividing cells in the healthy surrounding tissue directing new cells, all holding hands, towards the wound edge. Guzmán-Herrera and Mao (2020) describe that:

“Simultaneously, to restore the initial stratified architecture of the skin, cells rearrange, proliferate, flatten, elongate and migrate in the direction of injury.”

By growing lamellipodia and filopodia projections, cells move through the interstitial tissue spaces, as if they grow feet pushing them along.

Kinases activate myosin and actin within the cell cytoskeleton causing the cells to change shape and move (motility). (Mattila and Lappalainen, 2008). Cells move towards the wound, generating what is commonly called a ‘purse-string’ around the wound edge (Guzmán-Herrera and Mao 2020).

Video – Purse-string closure of a wound. Images were acquired by time-lapse confocal microscopy using a spinning disk confocal microscope. Adapted from (Hunter et al., 2015)

When the orchestra of tissue change becomes disorganised, would repair is disrupted.

Efficient and appropriate wound repair is negatively affected by poor health, smoking, stress (elevated blood cortisol and exhausted glucocorticoid receptors, the HPA axis) and even by a disrupted circadian rhythm (McDaniel and Browning, 2014) and (Hoyle et al. 2017).

As a manual soft tissue and myofascial therapist, treatment could target the down regulation of cortisol (stress) and may influence tissue repair. Zein-Hammoud and Standley (2019) investigated the use of ‘modelled’ myofascial release (MFR) in vitro. Their results concluded that MFR might reduce pro-inflammatory cytokines and may also assist in wound healing. MFR uses a sustained slow mechanical load, that stimulates more appropriate fibroblastic activity.

It is plausible, despite the above research being conducted in vitro and or on animals, that manual therapy, specifically MFR, could play a valuable role in early wound healing. MFR could attenuate the influence of scar tissue on healthy tissue and, it could also play a role in healthy scar tissue formation.

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REFERENCES

Guzmán-Herrera, A. Mao, y. (2020) ‘Polarity during tissue repair, a multiscale problem’, Current Opinion in Cell Biology, vol. 62, pp.31-36. Available at https://www.sciencedirect.com/science/article/pii/S0955067419300730(Accessed 10 November 2020).

Hoyle, N., Seinkmane, E., Putker, M., Feeney, K., Krogager, T., Chesham, J., Bray, L., Thomas, J., Dunn, K., Blaikley, J., O’Neil, J. (2017) ‘Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing’ Science Translational Medicine, nbr. 2274. Available at https://stm.sciencemag.org/content/scitransmed/9/415/eaal2774.full.pdf (Accessed 10 November 2020).

Hunter, V., Lee, D., Harris, T., Fernandez-Gonzalez, H. (2015) /Polarized E-cadherin endocytosis directs actomyosin remodeling during embryonic wound repair, J. Cell Biol, vol. 210, nbr. 5, pp. 801–816. Available at https://rupress.org/jcb/article/210/5/801/38293/Polarized-E-cadherin-endocytosis-directs (Accessed 10 November 2020).

Mattila, P. and Lappalainen, P. (2008) ‘Filopodia: molecular architecture and cellular functions’ Molecular Cell Biology, vol., 9, pp. 446-454. Available at https://www.nature.com/articles/nrm2406 (Accessed 10 November 2020).

McDaniel, J., Browning, K. (2014) ‘Smoking, Chronic Wound Healing, and Implications for Evidence-Based Practice’, J Wound Ostomy Continence Nurs., vol. 41, nbr., 5, pp. 415. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4241583/ (Accessed 12 November 2020).

Zein-Hammoud, M., Stabdley, P., (2019) ‘Fibroblast proliferation and collagen secretion are required for myofascial release-induced wound healing in three dimensional bioengineered tendons’, Journal of bodywork and Movement Therapies, vol., 42, nbr., 8, pp. 551-564 Available at https://www.bodyworkmovementtherapies.com/article/S1360-8592(15)00214-4/fulltext (Accessed 10 November 2020)

Flicker.com, ‘Indian Muntjac fibroblast cells’, Indian Muntjac cultured cells; DAPI nuclei, Alexa Fluor 488 Phalloidin actin, Mitotracker Red CMXRos; 63x/1.4. Imaged with ZEISS ApoTome.2, Axiocam 702 mono and Axio Imager (Picture). www.zeiss.com/axiocam. Sample courtesy of Michael W. Davidson, Florida State University. Available at https://www.flickr.com/photos/zeissmicro/24327908636/in/photolist-D4LTEC-CsVyZL-4S1HRs-dA3H48-7LVGq9-71rHqZ-2jPWmJq-uEAJbf-4vhkyR-WmBYJj-7EhiTR-6zAPKp-7LaQ9p-oJgwow-CP4CR6-ZgnQEH-2gLEPv4-awC8Q3-ymDFrP-8CFcnA-9PnMUR-C9zyS5-7dkpXq-CYNoGi-4DLKp5-DJykZd-26GToSE-25FpWJ7-B8jEQ-7gJyoA-7eHn4z-7tpXvY-7dgxXZ-7dkpZf-6btb3-6btb4-WgeiEX-a2Gcow-6btb7-eQ7LyA-6btb6-Nj1Pnz-MmbxTx-BQH2P-26LDeu4-24216dw-24216nj-26GToKq-26LDeS8-2hLww18  (Accessed 12 November 2020).

Ruth Duncan

Ruth Duncan

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