Wound Healing

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Wound healing


Wound healing can be divided into the four phases of inflammation, proliferation, re-epithelialization and tissue remodeling. So-called proteases play a key role in almost all phases. In the inflammatory phase, these enzymes (e.g. metalloproteinases, MMPs, serine proteases such as elastin) cleave the proteins of the damaged extracellular matrix (i.e. collagen, elastin, proteoglycans, etc.) so that new tissue can form. In the proliferation phase, they improve capillarization and when remodeling, they help to achieve good epidermal scarring.


It becomes dangerous if too many proteases are formed. Because then there is an undesirable breakdown of newly formed tissue and other proteins (eg growth factors). This extends the inflammatory process and destroys normal tissue [1] . Of course, certain inflammatory cytokines (TNF-alpha) are also suitable as an indicator of poor wound healing. In any case, both animal experiments and clinical studies have shown that wounds that do not progress in healing show increased protease activity [2] , [3] . Otherwise, proteases are of course part of the essential wound healing process.


With regard to the keratinocytes often mentioned in studies, these are cells of the epidermis (epidermis), which consists of 90% keratinocytes.

PEMF studies wound healing

From previous studies it is known that PEMF promote the proliferation, ie the rapid growth of keratinocytes [4] . A cell culture study demonstrated that - compared to a control culture - the cell-free area under PEMF decreased over time. Modulation of the metalloproteinases, the cytokines and the keratinocytes was also shown [5] .


An inflammation phase that is too long or excessive leads to hypertrophic scars, keloids or chronic wounds and ulcers. The important anti-inflammatory effects of PEMF in wound healing and poorly healing wounds are worked out in a review [6] .


Another review refers to the increasing prevalence, i.e. the frequency of chronic ulcers, which is around 0.3% of the population. As a result, three mechanisms of action of PEMF are emphasized: 1. An anti-inflammatory (anti-inflammatory) effect, in that the healing process by modulating cytokines results in a successful change from a pro-inflammatory to an anti-inflammatory state. 2. A new vessel-forming process that comes about through endothelial cell proliferation and the production of the FGF-2 growth factor (fibroblast growth factor). 3. A re-epithalization effect by stimulating collagen formation [7] .


PEMF studies wound healing post-op

It is known that a year after a total knee arthroplasty (TEP), a significant percentage of patients do not fully recover and continue to experience pain. In a study with 33 patients, these were randomized and assigned to a control and PEMF group (i.e. no placebo study). PEMF (1.5 mT / 75 Hz) was used postoperatively 4 hours a day for 60 days (portable, battery-operated device).


Result: Pain, knee swelling and functional score were significantly below that of the control group just 4 weeks after the TEP. Even after 6 months of follow-up, the pain was still significantly less. Three years after the operation, severe pain and isolated walking disabilities were expressed by a significantly smaller group of those treated with PEMF. The authors suspect that early inflammation reduction was crucial for the favorable outcome in the follow-up [8] .


In a study, the question was raised of the extent to which PEMF treatment can improve the therapeutic outcome of an implant that can be immediately loaded. For this purpose, 11 patients received four tilted implants in the upper and lower jaw and underwent immediate stress rehabilitation. For this, each patient received two special PEMF systems, one for each cheek. The systems, one of which was a placebo device, were then changed for randomization. Result: In most patients, 48 ​​hours after the operation, there was no difference between PEMF and placebo device in terms of swelling and pain. Although the study has some design deficits, it should be noted that it was not possible to influence the consequences of the operation here [9] .


In a randomized, placebo-controlled, double-blind study, 24 patients received PEMF treatment after a breast reduction surgery due to macromastia (breast enlargement above the norm). Result: Just one hour after using a PEMF, the average pain score (measured with VAS) decreased by 57% compared to placebo - and by 300% after 5 hours - which continued to have an effect for 48 hours. In addition, the need for pain relievers (opiates) decreased by 2.2 times in the verum group. In the PEMF group, the average IL-1 beta concentration in wound secretions was also 275% lower. There were no changes with regard to TNF-alpha, VEGF and FGF-2 [10] .


Study on breast reconstruction according to Mamma-Ca (procedure: pedicled TRAM flap plastic / here own tissue from the abdomen is used for breast building and also muscle tissue without interrupting the blood supply). This surgery is known to be very complex and painful. 32 patients in a randomized, placebo-controlled study: The result: 5 hours after the operation, the pain score (VAS) in the placebo group was 2 times higher and 72 hours afterwards 4 times higher than in the PEMF group, which also reduces pain medication consumption doubled in the placebo group and the average interleukin-1ß concentration in wound secretion was even 5 times higher. The authors come to the conclusion that PEMF can improve the speed and quality of wound healing after surgery [11] .


Also interesting is a randomized double-blind study on wound treatment after aesthetic breast augmentation. 42 healthy women were included, divided into three groups: a) bilateral PEMF treatment, b) bilateral placebo treatment and c) a breast with PEMF and a breast with placebo treatment. Result: Based on VAS scoring, the pain in the PEMF group decreased by almost a factor of 3 compared to placebo after the 3rd postoperative day and remained at this level until the 7th day. Correspondingly, the consumption of pain relievers decreased threefold [12] .


A special type of wound healing requires frostbite / frostbite that originates at great heights (Plateau Frostbites PF). The combination of cold and hypoxia (lack of oxygen) seems to cause more tissue damage than cold alone, which is obviously related to differences in microcirculation and histopathological changes in the different tissue layers [13] .


In a PEMF study, 69 rats were divided into three groups in a randomized study design: healthy animals, animals with partial frostbite (PTPF) on the back and those whose PTPF were treated with a PEMF daily. Result: The microcirculation in the PTPF-PEMF group recovered and wound healing improved 25% faster than in the PTPF rats. Histopathological examinations revealed an accelerated growth of various deeper tissue layers, which is related to the depth effect of magnetic fields [14] .


In a further randomized, double-blind and placebo-controlled PEMF study with 72 women, the possible pain reduction, analgesic consumption and wound healing after a section (caesarean section) were examined. The patients were divided into two groups (placebo and verum), each with 36 people. The survey was carried out on the VAS scale 2, 4, 6, 12 and 24 hours and 2, 4 and 7 days after the intervention. Result: In the active PEMF group, the postoperative pain was significantly weaker at all measured times than with placebo.


Significantly fewer women (36% vs. 72%) reported severe pain within 24 hours after the section. This was also reflected in pain medication consumption, which was 2.1 times lower in the PEMF group. After seven days, the wound healing process had progressed significantly better in those treated with PEMF, ie there were no exudates (inflammatory wound outflows), erythema (increased local blood flow to the skin tissue, for example as a result of inflammation) or edema. A high level of patient satisfaction has also been reported [15] .


PEMF leads to a significant reduction in pain in postoperative healing processes by means of anti-inflammation, edema removal and improved microcirculation, regardless of whether after endoprosthetic implantation, aesthetic breast surgery or a general postoperative wound treatment. Even sacral pressure ulcers that can hardly be improved with other therapeutic approaches can be proven to be curable within several months of regular use.


[1] Agren MS et al. Topical synthetic inhibitor of matrix metalloproteinases delays epidermal regeneration of human wounds. Exp Dermatol 2001; 10 (5): 337-48

[2] Beidler SK et al. Multiplexed analysis of matrix metalloproteinases in leg ulcer tissue of patients with chronic venous insufficiency before and after compression therapy. Wound Repair Regen 2008; 16 (5): 642-48

[3] Liu Y et al. Increased matrix metalloproteinase-9 predicts poor wound healing in diabetic foot ulcers. Diabetes cure 2009; 32 (1): 117-119

[4] Vianale G et al. Extremely low frequency electromagnetic field enhances human keratinocyte cell growth and decreases proinflammatory chemokine production. Brit J Dermatol 2008; 158 (6): 1180-1196

[5] Patruno A et al. Extremely low-frequency electromagnetic fields accelerates wound healing modulating MMP-9 and inflammatory cytokines. Cell prolif 2018 Jan 22: doi: 10.1111 / cpr.12432.

[6] Pesce M et al. Extremely low frequency electromagnetic field and wound healing: implication of cytokines as biological mediators.Eur Cytokine Netw 2013; 24 (1): 1-10

[7] Costin GE, Birlea SA, Norris DA. Trends in wound repair: cellular and molecular basis of regenerative therapy using electromagnetic fields. Curr Mol Med 2012; 12 (1): 14-26

[8] Adravanti P et al. Effect of pulsed electromagnetic field therapy in patients undergoing total knee arthroplasty: a randomized controlled trial. Int Orthop 2014; 38 (2): 397-403

[9] Menini M et al. Effects of pulsed electromagnetic fields on swelling and pain after implant surgery: a double-blind, randomized study. Int J Oral Maxillofac Surg 2016; 45 (3): 346-53

[10] Rohde C et al. Effects of pulsed electromagnetic fields on interleukin-1 beta and postoperative pain: a double-blind, placebo-controlled, pilot study in breast reduction patients. Plast Reconstr Surg 2010; 125 (6): 1620-9

[11] Rohde C et al. Pulsed electromagnetic fields reduce postoperative interleukin-1ß, pain, and inflammation: a double-blind, placebo-controlled study in TRAM flap breast reconstruction patients. Plast Reconstr Surg 2015; 135 (5): 808e-817e.

[12] Héden P, Pilla AA. Effects of pulsed electromagnetic fields on postoperative pain: a double-blind randomized pilot study in breast augmentation patients. Aesthetic Plast Surg 2008; 32 (4): 660-6

[13] Hu J et al. Pathophysiologic determination of frostbite under high altitude environment simulation in Sprague-Dawely Rats. Wilderness Environ Med 2016; 27 (3): 355-63

[14] Jiao M et al. Effects of low-frequency pulsed electromagnetic fields on plateau frostbite healing in rats. Wound Repair Regen 2016; 24 (6): 1015-1022

[15] Khooshideh M et al. Pulsed electromagnetic fields for postsurgical pain management in women undergoing caesarean section: a randomized, double-blind, placebo-controlled trial. Clin J Pain 2017; 33 (2): 42-147

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